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  1. Myopathy and hepatic lipidosis in weaned lambs due to vitamin E deficiency.

    Science.gov (United States)

    Menzies, Paula; Langs, Lisa; Boermans, Herman; Martin, John; McNally, John

    2004-03-01

    A sheep flock experienced losses in weaned lambs from myopathy and hepatic lipidosis. Investigation revealed painful ambulation, illthrift, and unexpected death in lambs with normal selenium levels, deficient vitamin E levels, and elevated muscle and liver enzyme levels. Vitamin E deficiency should be considered when investigating myopathy and illthrift in lambs.

  2. Myopathy and hepatic lipidosis in weaned lambs due to vitamin E deficiency

    OpenAIRE

    Menzies, Paula; Langs, Lisa; Boermans, Herman; Martin, John; McNally, John

    2004-01-01

    A sheep flock experienced losses in weaned lambs from myopathy and hepatic lipidosis. Investigation revealed painful ambulation, illthrift, and unexpected death in lambs with normal selenium levels, deficient vitamin E levels, and elevated muscle and liver enzyme levels. Vitamin E deficiency should be considered when investigating myopathy and illthrift in lambs.

  3. Hepatic lipidosis associated with cobalt deficiency in Omani goats.

    Science.gov (United States)

    Johnson, E H; Muirhead, D E; Annamalai, K; King, G J; Al-Busaidy, R; Hameed, M S

    1999-06-01

    Livers from 36 of 684 (5.3%) apparently healthy goats examined at an abattoir in the greater Muscat area of Oman exhibited gross pathological findings characterized by extremely pale, friable, fatty livers encompassing the entire organ. Histopathologically, diffuse hepatic lipidosis and occasional bile duct proliferation were observed. Periodic acid Schiff-positive, diastase-resistant pigment was observed in the macrophages lining the sinusoids. These histopathological lesions were consistent with those characteristic of ovine white liver disease. Cobalt analysis revealed that normal livers had six times more cobalt and a 3-fold less fat content than those measured in the fatty livers. This is the first report of an association between cobalt deficiency and hepatic lipidosis in Omani goats.

  4. Differences of Excess and Deficiency Zheng in Patients with Chronic Hepatitis B by Urinary Metabonomics

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    Shujun Sun

    2013-01-01

    Full Text Available Traditional Chinese medicine (TCM physicians stratify patients with the same disease into different subtypes in order to guide the appropriate treatment, which is called Zheng (TCM syndrome classification. Excess and deficiency ZHENG is a couple of basic ZHENGs of maladjusted body nature, reflecting the struggling state of human body and pathogenic factor and is important and prevalently exists in the ZHENG classification of many diseases. The present work using chronic hepatitis B (CHB as an entry point explored the substance connotation of excess and deficiency ZHENG with the metabonomic technology based on gas chromatography-mass spectrometry (GC-MS. The different substantial basis of two ZHENGs suggested that CHB patients could be categorized into two groups with diverse pathogenesis. The differential metabolites and disturbed pathways compared to not-obvious ZHENG characters patients (without ZHENG group/WZ were selected in both of the two ZHENGs. The ROC analysis demonstrated that five metabolites had a greater potential to be the clinic biomarkers of EZ or DZ. And excess ZHENG revealed a higher level of immune function than deficiency ZHENG. We are eager to transform the concept of traditional excess and deficiency ZHENGs to modern therapeutic approaches, with the prospect to help to promote personalized medicine.

  5. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    DEFF Research Database (Denmark)

    Gaini, Shahin

    2015-01-01

    A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode...... revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis...... and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....

  6. Hepatic glutathione and glutathione S-transferase in selenium deficiency and toxicity in the chick

    International Nuclear Information System (INIS)

    Kim, Y. S.

    1989-01-01

    First, the hepatic activity of GSH-T CDNB was increased only under conditions of severe oxidative stress produced by combined Se- and vitamin E (VE)-deficiency, indicating that VE also affects GSH metabolism. Second, the incorporation of 35 S-methionine into GSH and protein was about 4- and 2-fold higher, respectively, in Se- and VE-deficient chick hepatocytes as compared to controls. Third, chicks injected with the glutathione peroxidase (SeGSHpx) inhibitor, aurothioglucose (AuTG), showed increase hepatic GSH-T CDNB activity and plasma GSH concentration regardless of their Se status. Fourth, the effect of ascorbic acid (AA), on GSH metabolism was studied. Chicks fed 1000 ppm AA showed decreased hepatic GSH concentration compared to chicks fed no AA in a Se- and VE-deficient diet. Fifth, chicks fed excess Se showed increase hepatic activity of GSH-T CDNB and GSH concentration regardless of VE status

  7. Protection against high-fat diet-induced obesity in Helz2-deficient male mice due to enhanced expression of hepatic leptin receptor.

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    Yoshino, Satoshi; Satoh, Tetsurou; Yamada, Masanobu; Hashimoto, Koshi; Tomaru, Takuya; Katano-Toki, Akiko; Kakizaki, Satoru; Okada, Shuichi; Shimizu, Hiroyuki; Ozawa, Atsushi; Tuchiya, Takafumi; Ikota, Hayato; Nakazato, Yoichi; Mori, Munemasa; Matozaki, Takashi; Sasaki, Tsutomu; Kitamura, Tadahiro; Mori, Masatomo

    2014-09-01

    Obesity arises from impaired energy balance, which is centrally coordinated by leptin through activation of the long form of leptin receptor (Leprb). Obesity causes central leptin resistance. However, whether enhanced peripheral leptin sensitivity could overcome central leptin resistance remains obscure. A peripheral metabolic organ targeted by leptin is the liver, with low Leprb expression. We here show that mice fed a high-fat diet (HFD) and obese patients with hepatosteatosis exhibit increased expression of hepatic helicase with zinc finger 2, a transcriptional coactivator (Helz2), which functions as a transcriptional coregulator of several nuclear receptors, including peroxisome proliferator-activated receptor γ in vitro. To explore the physiological importance of Helz2, we generated Helz2-deficient mice and analyzed their metabolic phenotypes. Helz2-deficient mice showing hyperleptinemia associated with central leptin resistance were protected against HFD-induced obesity and had significantly up-regulated hepatic Leprb expression. Helz2 deficiency and adenovirus-mediated liver-specific exogenous Leprb overexpression in wild-type mice significantly stimulated hepatic AMP-activated protein kinase on HFD, whereas Helz2-deficient db/db mice lacking functional Leprb did not. Fatty acid-β oxidation was increased in Helz2-deficeint hepatocytes, and Helz2-deficient mice revealed increased oxygen consumption and decreased respiratory quotient in calorimetry analyses. The enhanced hepatic AMP-activated protein kinase energy-sensing pathway in Helz2-deficient mice ameliorated hyperlipidemia, hepatosteatosis, and insulin resistance by reducing lipogenic gene expression and stimulating lipid-burning gene expression in the liver. These findings together demonstrate that Helz2 deficiency ameliorates HFD-induced metabolic abnormalities by stimulating endogenous hepatic Leprb expression, despite central leptin resistance. Hepatic HELZ2 might be a novel target molecule for

  8. Hepatic S1P deficiency lowers plasma cholesterol levels in apoB-containing lipoproteins when LDLR function is compromised.

    Science.gov (United States)

    Basu, Debapriya; Huq, Afroza; Iqbal, Jahangir; Hussain, M Mahmood; Jiang, Xian-Cheng; Jin, Weijun

    2015-01-01

    Site-1 protease (S1P) is the key enzyme required for activation of the sterol regulatory element binding proteins (SREBPs) that govern lipid synthesis. While S1P has been speculated to influence plasma apoB-containing lipoprotein (Blp) metabolism, there has been little investigative work. LDL receptor (LDLR) is the major receptor for clearing plasma LDL cholesterol (LDL-c). Proprotein convertase subtilisin kexin type 9 (PCSK9) modulates LDL-c through post-translational degradation of the LDLR. A hepatic-specific knockdown (KD) of S1P was achieved using floxed S1P mouse models (S1P(f/f) and LDLR(-/-)S1P(f/f)) and hepatic expression of Cre recombinase. Lipids were measured in total plasma and size fractionated plasma using colorimetric assays. Realtime polymerase chain reaction, western blotting and ELISA were used to determine hepatic expression of key genes/protein. Plasmid mediated overexpression and siRNA mediated knockdown of genes were performed in mouse primary hepatocytes to determine the mechanistic basis of PCSK9 gene regulation. A hepatic-specific KD of S1P resulted in a 45 % and 38 % reduction in plasma total cholesterol and triglyceride levels, respectively. Hepatic S1P KD had a minimal effect on plasma Blp cholesterol (Blp-c) in S1P(f/f) mice, despite significantly reducing VLDL secretion. Notably, hepatic S1P KD decreased the LDL receptor (LDLR) mRNA expression by 50 %. However, the reduction in LDLR protein levels was less than that of mRNA expression, especially under fed conditions. Further assessment of hepatic S1P deficiency revealed that it increased LDLR protein stability in vivo. Mechanistically, hepatic S1P KD was shown to decrease the liver and plasma levels of the protein proprotein convertase subtilisin/kexin type 9 (PCSK9), which degrades LDLR protein. This effect was more prominent in the fed condition and sufficient to account for the discordance in LDLR mRNA and protein levels. Furthermore, hepatic S1P was shown to regulate PCSK9

  9. Ultrasonographic evaluation to diagnose hepatic lipidosis in Egyptian Zaraibi goats with vitamin B12 deficiency

    OpenAIRE

    Sabry A. El-Khodery; Hussein S. Hussein; Mohamed E. El-Boshy; Medhat N. Nassif

    2011-01-01

    As little is known about the ultrasonographic features of hepatic lipidosis (white liver disease) in goats, this study was undertaken to evaluate the use of ultrasound for the diagnosis of hepatic lipidosis associated with vitamin B12 (cyanocobalamin) deficiency in Egyptian Zaraibi goats. A total of 38 goats (28 with weight loss, diarrhoea and anaemia and 10 clinically healthy) were studied. Twenty-one goats were demonstrated to have cobalt and cyanocobalamin deficiency (0.33 ± 0.12 μmol/l an...

  10. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    Directory of Open Access Journals (Sweden)

    Shahin Gaini

    2015-01-01

    Full Text Available A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine.

  11. Reduced hepatic tumor incidence in cyclin G1-deficient mice

    DEFF Research Database (Denmark)

    Jensen, Michael Rugaard; Factor, Valentina M; Fantozzi, Anna

    2003-01-01

    found that the p53 levels in the cyclin G1-deficient mice are 2-fold higher that in wild-type mice. Moreover, we showed that treatment of mice with the alkylating agent 1,4-bis[N,N'-di(ethylene)-phosphamide]piperazine (Dipin), followed by partial hepatectomy, decreased G1-S transition in cyclin G1-null...

  12. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Related Liver Disease Alpha-1 Antitrypsin Deficiency Autoimmune Hepatitis Benign Liver Tumors Biliary Atresia Cirrhosis of the ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of ...

  13. Ultrasonographic evaluation to diagnose hepatic lipidosis in Egyptian Zaraibi goats with vitamin B12 deficiency

    Directory of Open Access Journals (Sweden)

    Sabry A. El-Khodery

    2011-01-01

    Full Text Available As little is known about the ultrasonographic features of hepatic lipidosis (white liver disease in goats, this study was undertaken to evaluate the use of ultrasound for the diagnosis of hepatic lipidosis associated with vitamin B12 (cyanocobalamin deficiency in Egyptian Zaraibi goats. A total of 38 goats (28 with weight loss, diarrhoea and anaemia and 10 clinically healthy were studied. Twenty-one goats were demonstrated to have cobalt and cyanocobalamin deficiency (0.33 ± 0.12 μmol/l and 0.17 ± 0.10 μg/l, respectively. Goats were examined with a real-time ultrasound system using a 5-MHz convex transducer. Ultrasound-guided liver biopsies and blood samples were obtained from each animal at examination. Based on the histopathological findings, diseased goats were classified as having mild (n = 6, moderate (n = 6 or severe lipidosis (n = 9. Ultrasonographic-hepatic changes were recorded in 19 (90.4% out of 21 goats. Severe lipidosis showed diffuse hyper-echogenicity of hepatic parenchyma. However, focal hyper-echoic lesions with various shapes, sizes and positions were visualized in mild and moderate lipidosis. Liver size increased significantly (P < 0.05 in severely affected goats compared with the controls. Histopathologically, macrovacuolations, congestion of hepatic sinusoids and infiltration of the portal area with inflammatory cells and connective tissues were evident in moderate and severely affected cases. There were varying degrees of anaemia, hypoglycemia and hypoproteinemia with significant increases (P < 0.05 of aspartate aminotransferase (AST and alkaline phosphatase (ALP in diseased animals compared with the controls. In conclusion, ultrasound may be a useful diagnostic tool in goats with suspected hepatic lipidosis associated with vitamin B12 deficiency.

  14. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

    Science.gov (United States)

    Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

    2015-07-01

    Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

  15. Severe riboflavin deficiency induces alterations in the hepatic proteome of starter Pekin ducks.

    Science.gov (United States)

    Tang, Jing; Hegeman, Maria A; Hu, Jian; Xie, Ming; Shi, Wenbiao; Jiang, Yong; de Boer, Vincent; Guo, Yuming; Hou, Shuisheng; Keijer, Jaap

    2017-11-01

    Suboptimal vitamin B2 status is encountered globally. Riboflavin deficiency depresses growth and results in a fatty liver. The underlying mechanisms remain to be established and an overview of molecular alterations is lacking. We investigated hepatic proteome changes induced by riboflavin deficiency to explain its effects on growth and hepatic lipid metabolism. In all, 360 1-d-old Pekin ducks were divided into three groups of 120 birds each, with twelve replicates and ten birds per replicate. For 21 d, the ducks were fed ad libitum a control diet (CAL), a riboflavin-deficient diet (RD) or were pair-fed with the control diet to the mean daily intake of the RD group (CPF). When comparing RD with CAL and CPF, growth depression, liver enlargement, liver lipid accumulation and enhanced liver SFA (C6 : 0, C12 : 0, C16 : 0, C18 : 0) were observed. In RD, thirty-two proteins were enhanced and thirty-one diminished (>1·5-fold) compared with CAL and CPF. Selected proteins were confirmed by Western blotting. The diminished proteins are mainly involved in fatty acid β-oxidation and the mitochondrial electron transport chain (ETC), whereas the enhanced proteins are mainly involved in TAG and cholesterol biosynthesis. RD causes liver lipid accumulation and growth depression probably by impairing fatty acid β-oxidation and ETC. These findings contribute to our understanding of the mechanisms of liver lipid metabolic disorders due to RD.

  16. Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing.

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    Zhou, Can-Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao-Bing; Li, Guo-Qiang; Song, Jie; Xu, Tian-Ying; Li, Zhi-Yong; Guan, Yun-Feng; Wang, Pei; Miao, Chao-Yu

    2016-08-01

    Ageing is an important risk factor of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD(+) ), a ubiquitous coenzyme, links ageing with NAFLD. Hepatic concentrations of NAD(+) , protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD(+) biosynthesis, were compared in middle-aged and aged mice or patients. The influences of NAD(+) decline on the steatosis and steatohepatitis were evaluated in wild-type and H247A dominant-negative, enzymically-inactive NAMPT transgenic mice (DN-NAMPT) given normal or high-fat diet (HFD). Hepatic NAD(+) level decreased in aged mice and humans. NAMPT-controlled NAD(+) salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle-age DN-NAMPT mice displayed systemic NAD(+) reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro-inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α-SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD(+) precursor, completely corrected these NAFLD phenotypes induced by NAD(+) deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes. These results provide the first evidence that ageing-associated NAD(+) deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD(+) substrates may be a promising therapeutic strategy to prevent and treat NAFLD. © 2016 The British Pharmacological Society.

  17. Hepatic NAD+ deficiency as a therapeutic target for non‐alcoholic fatty liver disease in ageing

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    Zhou, Can‐Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao‐Bing; Li, Guo‐Qiang; Song, Jie; Xu, Tian‐Ying; Li, Zhi‐Yong; Guan, Yun‐Feng

    2016-01-01

    Abstract Background and Purpose Ageing is an important risk factor of non‐alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD+), a ubiquitous coenzyme, links ageing with NAFLD. Experimental Approach Hepatic concentrations of NAD+, protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD+ biosynthesis, were compared in middle‐aged and aged mice or patients. The influences of NAD+ decline on the steatosis and steatohepatitis were evaluated in wild‐type and H247A dominant‐negative, enzymically‐inactive NAMPT transgenic mice (DN‐NAMPT) given normal or high‐fat diet (HFD). Key Results Hepatic NAD+ level decreased in aged mice and humans. NAMPT‐controlled NAD+ salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle‐age DN‐NAMPT mice displayed systemic NAD+ reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro‐inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α‐SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD+ precursor, completely corrected these NAFLD phenotypes induced by NAD+ deficiency alone or HFD, whereas adenovirus‐mediated SIRT1 overexpression only partially rescued these phenotypes. Conclusions and Implications These results provide the first evidence that ageing‐associated NAD+ deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD+ substrates may be a promising therapeutic strategy to prevent and treat NAFLD. PMID:27174364

  18. An iron-deficient diet stimulates the onset of the hepatitis due to hepatic copper deposition in the Long-Evans Cinnamon (LEC) rat

    Energy Technology Data Exchange (ETDEWEB)

    Sugawara, Naoki; Sugawara, Chieko [Sapporo Medical Univ. (Japan). Dept. of Public Health

    1999-09-01

    To study effects of dietary Cu and Fe levels on the onset of hepatitis in Long-Evans Cinnamon (LEC) rats, female rats (40 days old) were fed a semipurified diet containing 0.1 or 10 mg Cu/kg and 1.5 or 150 mg Fe/kg in a 2 x 2 factorial arrangement for 35 days. At 75 days after birth, LEC rats (+Cu-Fe) fed a Cu-sufficient but Fe-deficient diet (Cu, 10 mg/kg; Fe, 1.5 mg/kg) showed jaundice, with lethargy, anorexia, and malaise. The biochemical variables relating to liver function were significantly increased compared to three other groups, a Cu- and Fe-deficient (-Cu-Fe) group, a Cu-deficient but Fe-sufficient (-Cu+Fe) group, and a Cu and Fe sufficient (+Cu+Fe) group. Furthermore, the +Cu-Fe rat liver showed massive necrosis with huge nuclei. The other three groups presented no biochemical and histological findings of hepatitis. Hepatic Cu and metallothionein concentrations were 289 {+-} 87 (mean {+-} SD) {mu}g/g liver and 8.7 {+-} 1.8 mg/g liver, respectively, in the +Cu-Fe rats. However, in the +Cu+Fe group the values were 196 {+-} 28 {mu}g Cu/g liver and 10.8 {+-} 1.0 mg/g liver. Hepatic Fe deposition was not influenced significantly by the dietary Cu level. The +Cu-Fe group with jaundice showed the highest free Cu concentration in the liver among the four groups, but the hepatic free Fe concentration was similar to those in the -Cu+Fe and +Cu+Fe groups. Our results indicate that an Fe-deficient diet enhances the deposition of hepatic Cu due to increased absorption of Cu from the gastrointestinal tract. This deposition stimulated the onset of hepatitis. (orig.)

  19. Impairments of hepatic gluconeogenesis and ketogenesis in PPARα-deficient neonatal mice.

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    Cotter, David G; Ercal, Baris; d'Avignon, D André; Dietzen, Dennis J; Crawford, Peter A

    2014-07-15

    Peroxisome proliferator activated receptor-α (PPARα) is a master transcriptional regulator of hepatic metabolism and mediates the adaptive response to fasting. Here, we demonstrate the roles for PPARα in hepatic metabolic adaptations to birth. Like fasting, nutrient supply is abruptly altered at birth when a transplacental source of carbohydrates is replaced by a high-fat, low-carbohydrate milk diet. PPARα-knockout (KO) neonatal mice exhibit relative hypoglycemia due to impaired conversion of glycerol to glucose. Although hepatic expression of fatty acyl-CoA dehydrogenases is imparied in PPARα neonates, these animals exhibit normal blood acylcarnitine profiles. Furthermore, quantitative metabolic fate mapping of the medium-chain fatty acid [(13)C]octanoate in neonatal mouse livers revealed normal contribution of this fatty acid to the hepatic TCA cycle. Interestingly, octanoate-derived carbon labeled glucose uniquely in livers of PPARα-KO neonates. Relative hypoketonemia in newborn PPARα-KO animals could be mechanistically linked to a 50% decrease in de novo hepatic ketogenesis from labeled octanoate. Decreased ketogenesis was associated with diminished mRNA and protein abundance of the fate-committing ketogenic enzyme mitochondrial 3-hydroxymethylglutaryl-CoA synthase (HMGCS2) and decreased protein abundance of the ketogenic enzyme β-hydroxybutyrate dehydrogenase 1 (BDH1). Finally, hepatic triglyceride and free fatty acid concentrations were increased 6.9- and 2.7-fold, respectively, in suckling PPARα-KO neonates. Together, these findings indicate a primary defect of gluconeogenesis from glycerol and an important role for PPARα-dependent ketogenesis in the disposal of hepatic fatty acids during the neonatal period. Copyright © 2014 the American Physiological Society.

  20. Hepatic glucose-6-phosphatase-α deficiency leads to metabolic reprogramming in glycogen storage disease type Ia.

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    Cho, Jun-Ho; Kim, Goo-Young; Mansfield, Brian C; Chou, Janice Y

    2018-04-15

    Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), a key enzyme in endogenous glucose production. This autosomal recessive disorder is characterized by impaired glucose homeostasis and long-term complications of hepatocellular adenoma/carcinoma (HCA/HCC). We have shown that hepatic G6Pase-α deficiency-mediated steatosis leads to defective autophagy that is frequently associated with carcinogenesis. We now show that hepatic G6Pase-α deficiency also leads to enhancement of hepatic glycolysis and hexose monophosphate shunt (HMS) that can contribute to hepatocarcinogenesis. The enhanced hepatic glycolysis is reflected by increased lactate accumulation, increased expression of many glycolytic enzymes, and elevated expression of c-Myc that stimulates glycolysis. The increased HMS is reflected by increased glucose-6-phosphate dehydrogenase activity and elevated production of NADPH and the reduced glutathione. We have previously shown that restoration of hepatic G6Pase-α expression in G6Pase-α-deficient liver corrects metabolic abnormalities, normalizes autophagy, and prevents HCA/HCC development in GSD-Ia. We now show that restoration of hepatic G6Pase-α expression normalizes both glycolysis and HMS in GSD-Ia. Moreover, the HCA/HCC lesions in L-G6pc-/- mice exhibit elevated levels of hexokinase 2 (HK2) and the M2 isoform of pyruvate kinase (PKM2) which play an important role in aerobic glycolysis and cancer cell proliferation. Taken together, hepatic G6Pase-α deficiency causes metabolic reprogramming, leading to enhanced glycolysis and elevated HMS that along with impaired autophagy can contribute to HCA/HCC development in GSD-Ia. Published by Elsevier Inc.

  1. Heterozygous deficiency of endoglin decreases insulin and hepatic triglyceride levels during high fat diet.

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    Daniel Beiroa

    Full Text Available Endoglin is a transmembrane auxiliary receptor for transforming growth factor-beta (TGF-beta that is predominantly expressed on proliferating endothelial cells. It plays a wide range of physiological roles but its importance on energy balance or insulin sensitivity has been unexplored. Endoglin deficient mice die during midgestation due to cardiovascular defects. Here we report for first time that heterozygous endoglin deficiency in mice decreases high fat diet-induced hepatic triglyceride content and insulin levels. Importantly, these effects are independent of changes in body weight or adiposity. At molecular level, we failed to detect relevant changes in the insulin signalling pathway at basal levels in liver, muscle or adipose tissues that could explain the insulin-dependent effect. However, we found decreased triglyceride content in the liver of endoglin heterozygous mice fed a high fat diet in comparison to their wild type littermates. Overall, our findings indicate that endoglin is a potentially important physiological mediator of insulin levels and hepatic lipid metabolism.

  2. Interleukin-10 Genotype Correlated to Deficiency Syndrome in Hepatitis B Cirrhosis

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    Qing-Ya Li

    2012-01-01

    Full Text Available Traditional Chinese medicine (TCM syndrome is an important basis for TCM diagnosis and treatment. As Child-Pugh classification as well as compensation and decompensation phase in liver cirrhosis, it is also an underlying clinical classification. In this paper, we investigated the correlation between single nucleotide polymorphisms (SNPs of Interleukin-10 (IL-10 and TCM syndromes in patients with hepatitis B cirrhosis (HBC. Samples were obtained from 343 HBC patients in China. Three SNPs of IL-10 (−592A/C, −819C/T, and −1082A/G were detected with polymerase chain-reaction-ligase detection reaction (PCR-LDR. The result showed the SNP-819C/T was significantly correlated with Deficiency syndrome (P=0.031, but none of the 3 loci showed correlation either with Child-Pugh classification and phase in HBC patients. The logistic regression analysis showed that the Excess syndrome was associated with dizzy and spider nevus, and the Deficiency syndrome was associated with dry eyes, aversion to cold, IL-10-819C/T loci, and IL-10-1082A/G loci. The odds ratio (OR value at IL-10-819C/T was 4.022. The research results suggested that IL-10-819C/T locus (TC plus CC genotype is probably a risk factor in the occurrence of Deficiency syndrome in HBC patients.

  3. Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient PEX2 Zellweger mice

    NARCIS (Netherlands)

    Keane, Megan H.; Overmars, Henk; Wikander, Thomas M.; Ferdinandusse, Sacha; Duran, Marinus; Wanders, Ronald J. A.; Faust, Phyllis L.

    2007-01-01

    The marked deficiency of peroxisomal organelle assembly in the PEX2(-/-) mouse model for Zellweger syndrome provides a unique opportunity to developmentally and biochemically characterize hepatic disease progression and bile acid products. The postnatal survival of homozygous mutants enabled us to

  4. Pancreatic injury in hepatic alcohol dehydrogenase-deficient deer mice after subchronic exposure to ethanol

    International Nuclear Information System (INIS)

    Kaphalia, Bhupendra S.; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Wu Hai; Boor, Paul J.; Ansari, G.A. Shakeel

    2010-01-01

    Pancreatitis caused by activation of digestive zymogens in the exocrine pancreas is a serious chronic health problem in alcoholic patients. However, mechanism of alcoholic pancreatitis remains obscure due to lack of a suitable animal model. Earlier, we reported pancreatic injury and substantial increases in endogenous formation of fatty acid ethyl esters (FAEEs) in the pancreas of hepatic alcohol dehydrogenase (ADH)-deficient (ADH - ) deer mice fed 4% ethanol. To understand the mechanism of alcoholic pancreatitis, we evaluated dose-dependent metabolism of ethanol and related pancreatic injury in ADH - and hepatic ADH-normal (ADH + ) deer mice fed 1%, 2% or 3.5% ethanol via Lieber-DeCarli liquid diet daily for 2 months. Blood alcohol concentration (BAC) was remarkably increased and the concentration was ∼ 1.5-fold greater in ADH - vs. ADH + deer mice fed 3.5% ethanol. At the end of the experiment, remarkable increases in pancreatic FAEEs and significant pancreatic injury indicated by the presence of prominent perinuclear space, pyknotic nuclei, apoptotic bodies and dilation of glandular ER were found only in ADH - deer mice fed 3.5% ethanol. This pancreatic injury was further supported by increased plasma lipase and pancreatic cathepsin B (a lysosomal hydrolase capable of activating trypsinogen), trypsinogen activation peptide (by-product of trypsinogen activation process) and glucose-regulated protein 78 (endoplasmic reticulum stress marker). These findings suggest that ADH-deficiency and high alcohol levels in the body are the key factors in ethanol-induced pancreatic injury. Therefore, determining how this early stage of pancreatic injury advances to inflammation stage could be important for understanding the mechanism(s) of alcoholic pancreatitis.

  5. Branched-chain amino acids alleviate hepatic steatosis and liver injury in choline-deficient high-fat diet induced NASH mice.

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    Honda, Takashi; Ishigami, Masatoshi; Luo, Fangqiong; Lingyun, Ma; Ishizu, Yoji; Kuzuya, Teiji; Hayashi, Kazuhiko; Nakano, Isao; Ishikawa, Tetsuya; Feng, Guo-Gang; Katano, Yoshiaki; Kohama, Tomoya; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Goto, Hidemi; Hirooka, Yoshiki

    2017-04-01

    For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis. In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH. Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation. Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (PBCAA was significantly lower than those of CDHF-control. BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Increased hepatic cholesterol esterification with essential fatty acid deficiency (EFAD): relationship to plasma lipoprotein (LP) cholesterol content

    International Nuclear Information System (INIS)

    Ney, D.M.; Ziboh, V.A.; Schneeman, B.O.

    1986-01-01

    EFAD in the rat is associated with hepatic accumulation of esterified cholesterol and altered distribution of cholesterol between plasma and hepatic tissue. Little is known regarding the impact of EFAD on LP composition. To determine the relationship between hepatic cholesterol esterification and plasma lP composition in control (C) and EFAD male Wistar rats, the authors induced EFAD with continuous intragastric (IG) infusion of EFA-free solutions containing 3.5% of calories as triolein for 7 and 14 days. C animals received IG infusion of solutions containing 3.5% of calories as linoleic acid. Data in the EFAD groups reveal: (i) marked decreases in hepatic EFAs and increases in monoenoic acids; (ii) progressive increases in hepatic content of triglyceride and esterified cholesterol with 7 and 14 days of feeding; (iii) assay of acyl CoA:cholesterol acyltransferase activity in hepatic tissue using 14 C-cholesterol demonstrates an increase in hepatic cholesterol esterification when compared to C animals. Increased hepatic cholesterol esterification correlates with elevated levels of esterified cholesterol in plasma VLDL and HDL particles. These data indicate that the elevated levels of cholesterol esters in LP particles is due, at least in part, to increased hepatic cholesterol esterification with EFAD

  7. iPLA2β deficiency attenuates obesity and hepatic steatosis in ob/ob mice through hepatic fatty-acyl phospholipid remodeling.

    Science.gov (United States)

    Deng, Xiuling; Wang, Jiliang; Jiao, Li; Utaipan, Tanyarath; Tuma-Kellner, Sabine; Schmitz, Gerd; Liebisch, Gerhard; Stremmel, Wolfgang; Chamulitrat, Walee

    2016-05-01

    PLA2G6 or GVIA calcium-independent PLA2 (iPLA2β) is identified as one of the NAFLD modifier genes in humans, and thought to be a target for NAFLD therapy. iPLA2β is known to play a house-keeping role in phospholipid metabolism and remodeling. However, its role in NAFLD pathogenesis has not been supported by results obtained from high-fat feeding of iPLA2β-null (PKO) mice. Unlike livers of human NAFLD and genetically obese rodents, fatty liver induced by high-fat diet is not associated with depletion of hepatic phospholipids. We therefore tested whether iPLA2β could regulate obesity and hepatic steatosis in leptin-deficient mice by cross-breeding PKO with ob/ob mice to generate ob/ob-PKO mice. Here we observed an improvement in ob/ob-PKO mice with significant reduction in serum enzymes, lipids, glucose, insulin as well as improved glucose tolerance, and reduction in islet hyperplasia. The improvement in hepatic steatosis measured by liver triglycerides, fatty acids and cholesterol esters was associated with decreased expression of PPARγ and de novo lipogenesis genes, and the reversal of β-oxidation gene expression. Notably, ob/ob livers contained depleted levels of lysophospholipids and phospholipids, and iPLA2β deficiency in ob/ob-PKO livers lowers the former, but replenished the latter particularly phosphatidylethanolamine (PE) and phosphatidylcholine (PC) that contained arachidonic (AA) and docosahexaenoic (DHA) acids. Compared with WT livers, PKO livers also contained increased PE and PC containing AA and DHA. Thus, iPLA2β deficiency protected against obesity and ob/ob fatty liver which was associated with hepatic fatty-acyl phospholipid remodeling. Our results support the deleterious role of iPLA2β in severe obesity associated NAFLD. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID).

    Science.gov (United States)

    Kühl, J S; Schwarz, K; Münch, A; Schmugge, M; Pekrun, A; Meisel, C; Wahn, V; Ebell, W; von Bernuth, H

    2011-03-01

    Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Delayed plasma clearance and hepatic uptake of lymph chylomicron 14C-cholesterol in marginally zinc-deficient rats

    International Nuclear Information System (INIS)

    Koo, S.I.; Algilani, K.; Norvell, J.E.; Henderson, D.A.

    1986-01-01

    Previously, chylomicrons from marginally zinc-deficient rats were shown to be abnormally large, with markedly reduced levels of apoproteins C and E. In the present study, effects of such changes on the plasma clearance and hepatic uptake of chylomicron cholesterol were investigated in rats fed 3 ppm of zinc (ZD), as compared with those fed 30 ppm of zinc (CT). The rate of plasma clearance was determined by plasma 14C-radioactivity at different intervals after intravenous injection of lymph chylomicrons labeled in vivo with 14C-cholesterol. The 14C-clearance curves were nonlinear, consisting of an initial rapid phase followed by a slow phase of clearance. The initial 14C-clearance was significantly (p less than 0.05) delayed whether the labeled chylomicrons from ZD donors were injected into ZD or CT recipients. The hepatic 14C-recovery in extracted lipids was also significantly lower in ZD rats. The present data provide first evidence that a marginal level of zinc deficiency produces a significant delay in the plasma clearance and hepatic uptake of chylomicron cholesterol. This may be attributable in part to the molecular alterations of chylomicrons induced by zinc deficiency

  10. Hepatitis

    Science.gov (United States)

    ... most common types of viral hepatitis. What Is Hepatitis A? For kids, hep A is the most common ... they recover, it does not come back. Can Hepatitis A Be Prevented? The following will help keep people ...

  11. SGLT5 Reabsorbs Fructose in the Kidney but Its Deficiency Paradoxically Exacerbates Hepatic Steatosis Induced by Fructose

    Science.gov (United States)

    Fukuzawa, Taku; Fukazawa, Masanori; Ueda, Otoya; Shimada, Hideaki; Kito, Aki; Kakefuda, Mami; Kawase, Yosuke; Wada, Naoko A.; Goto, Chisato; Fukushima, Naoshi; Jishage, Kou-ichi; Honda, Kiyofumi; King, George L.; Kawabe, Yoshiki

    2013-01-01

    Although excessive fructose intake is epidemiologically linked with dyslipidemia, obesity, and diabetes, the mechanisms regulating plasma fructose are not well known. Cells transfected with sodium/glucose cotransporter 5 (SGLT5), which is expressed exclusively in the kidney, transport fructose in vitro; however, the physiological role of this transporter in fructose metabolism remains unclear. To determine whether SGLT5 functions as a fructose transporter in vivo, we established a line of mice lacking the gene encoding SGLT5. Sodium-dependent fructose uptake disappeared in renal brush border membrane vesicles from SGLT5-deficient mice, and the increased urinary fructose in SGLT5-deficient mice indicated that SGLT5 was the major fructose reabsorption transporter in the kidney. From this, we hypothesized that urinary fructose excretion induced by SGLT5 deficiency would ameliorate fructose-induced hepatic steatosis. To test this hypothesis we compared SGLT5-deficient mice with wild-type mice under conditions of long-term fructose consumption. Paradoxically, however, fructose-induced hepatic steatosis was exacerbated in the SGLT5-deficient mice, and the massive urinary fructose excretion was accompanied by reduced levels of plasma triglycerides and epididymal fat but fasting hyperinsulinemia compared with fructose-fed wild-type mice. There was no difference in food consumption, water intake, or plasma fructose between the two types of mice. No compensatory effect by other transporters reportedly involved in fructose uptake in the liver and kidney were indicated at the mRNA level. These surprising findings indicated a previously unrecognized link through SGLT5 between renal fructose reabsorption and hepatic lipid metabolism. PMID:23451068

  12. Inhibition of PTP1B Restores IRS1-Mediated Hepatic Insulin Signaling in IRS2-Deficient Mice

    Science.gov (United States)

    González-Rodríguez, Águeda; Gutierrez, Jose A. Mas; Sanz-González, Silvia; Ros, Manuel; Burks, Deborah J.; Valverde, Ángela M.

    2010-01-01

    OBJECTIVE Mice with complete deletion of insulin receptor substrate 2 (IRS2) develop hyperglycemia, impaired hepatic insulin signaling, and elevated gluconeogenesis, whereas mice deficient for protein tyrosine phosphatase (PTP)1B display an opposing hepatic phenotype characterized by increased sensitivity to insulin. To define the relationship between these two signaling pathways in the regulation of liver metabolism, we used genetic and pharmacological approaches to study the effects of inhibiting PTP1B on hepatic insulin signaling and expression of gluconeogenic enzymes in IRS2−/− mice. RESEARCH DESIGN AND METHODS We analyzed glucose homeostasis and insulin signaling in liver and isolated hepatocytes from IRS2−/− and IRS2−/−/PTP1B−/− mice. Additionally, hepatic insulin signaling was assessed in control and IRS2−/− mice treated with resveratrol, an antioxidant present in red wine. RESULTS In livers of hyperglycemic IRS2−/− mice, the expression levels of PTP1B and its association with the insulin receptor (IR) were increased. The absence of PTP1B in the double-mutant mice restored hepatic IRS1-mediated phosphatidylinositol (PI) 3-kinase/Akt/Foxo1 signaling. Moreover, resveratrol treatment of hyperglycemic IRS2−/− mice decreased hepatic PTP1B mRNA and inhibited PTP1B activity, thereby restoring IRS1-mediated PI 3-kinase/Akt/Foxo1 signaling and peripheral insulin sensitivity. CONCLUSIONS By regulating the phosphorylation state of IR, PTB1B determines sensitivity to insulin in liver and exerts a unique role in the interplay between IRS1 and IRS2 in the modulation of hepatic insulin action. PMID:20028942

  13. A rare case of Addison's disease, hepatitis, thyreoiditis, positive IgG anti-tissue transglutaminase antibodies and partial IgA deficiency.

    Science.gov (United States)

    Baleva, Marta P; Mihaylova, Snejina; Yankova, Petja; Atanasova, Iliana; Nikolova-Vlahova, Milena; Naumova, Elissaveta

    2016-01-01

    Selective IgA deficiency (IgAD) is the most prevalent type of primary immune deficiencies, but partial IgA deficiency is even more common. Addison's disease is a rare condition associated with primary adrenal insufficiency due to infection or autoimmune destruction of the adrenals. The association between IgA deficiency and Addison's disease is very rare. We observed a 22-year-old male patient with marked darkening of the skin, especially on the palms and areolae, jaundice on the skin and sclera, astheno-adynamia, hypotension (80/50 mm Hg), and pain in the right hypochondrium. The laboratory investigations revealed increased serum levels of total and indirect bilirubin, AST, ALT, GGT and LDH, negative HBsAg, anti-HBc IgM, anti-HCV and anti-HAV IgM, very low serum IgA levels (0.16 g/l) with normal IgG and IgM, negative ANA, ANCA, AMA, LKM-1, anti-GAD-60, anti-IA-2, anti-thyroglobulin antibodies, a mild increase in anti-TPO antibodies titer, a marked increase in IgG anti-tissue transglutaminase antibodies, with no typical changes in cellular immunity, negative T-SPOT-TB test, HLA - A*01; B*08; DRB1*03; DQB1*02, karyotype - 46, XY. We present a rare case of partial IgA deficiency with Addison's disease, hepatitis, thyroiditis and positive anti-tissue transglutaminase antibodies. IgAD and some autoimmune disorders share several predisposing HLA genes, thus explaining the increased prevalence of IgAD in certain patient groups.

  14. Ascorbic acid deficiency stimulates hepatic expression of inflammatory chemokine, cytokine-induced neutrophil chemoattractant-1, in scurvy-prone ODS rats.

    Science.gov (United States)

    Horio, Fumihiko; Kiyama, Keiichiro; Kobayashi, Misato; Kawai, Kaori; Tsuda, Takanori

    2006-02-01

    ODS rat has a hereditary defect in ascorbic acid biosynthesis and is a useful animal model for elucidating the physiological role of ascorbic acid. We previously demonstrated by using ODS rats that ascorbic acid deficiency changes the hepatic gene expression of acute phase proteins, as seen in acute inflammation. In this study, we investigated the effects of ascorbic acid deficiency on the production of inflammatory chemokine, cytokine-induced neutrophil chemoattractant-1 (CINC-1), in ODS rats. Male ODS rats (6 wk of age) were fed a basal diet containing ascorbic acid (300 mg/kg diet) or a diet without ascorbic acid for 14 d. Obvious symptoms of scurvy were not observed in the ascorbic acid-deficient rats. Ascorbic acid deficiency significantly elevated the serum concentration of CINC-1 on d 14. The liver and spleen CINC-1 concentrations in the ascorbic acid-deficient rats were significantly elevated to 600% and 180% of the respective values in the control rats. However, the lung concentration of CINC-1 was not affected by ascorbic acid deficiency. Ascorbic acid deficiency significantly elevated the hepatic mRNA level of CINC-1 (to 480% of the value in the control rats), but not the lung mRNA level. These results demonstrate that ascorbic acid deficiency elevates the serum, liver and spleen concentrations of CINC-1 as seen in acute inflammation, and suggest that ascorbic acid deficiency stimulate the hepatic CINC-1 gene expression.

  15. Influence of depleted uranium on hepatic cholesterol metabolism in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Souidi, M; Racine, R; Grandcolas, L; Grison, S; Stefani, J; Gourmelon, P; Lestaevel, P

    2012-04-01

    Depleted uranium (DU) is uranium with a lower content of the fissile isotope U-235 than natural uranium. It is a radioelement and a waste product from the enrichment process of natural uranium. Because of its very high density, it is used in the civil industry and for military purposes. DU exposure can affect many vital systems in the human body, because in addition to being weakly radioactive, uranium is a toxic metal. It should be emphasized that, to be exposed to radiation from DU, you have to eat, drink, or breathe it, or get it on your skin. This particular study is focusing on the health effects of DU for the cholesterol metabolism. Previous studies on the same issue have shown that the cholesterol metabolism was modulated at molecular level in the liver of laboratory rodents contaminated for nine months with DU. However, this modulation was not correlated with some effects at organs or body levels. It was therefore decided to use a "pathological model" such as hypercholesterolemic apolipoprotein E-deficient laboratory mice in order to try to clarify the situation. The purpose of the present study is to assess the effects of a chronic ingestion (during 3 months) of a low level DU-supplemented water (20 mg L(-1)) on the above mentioned mice in order to determine a possible contamination effect. Afterwards the cholesterol metabolism was studied in the liver especially focused on the gene expressions of cholesterol-catabolising enzymes (CYP7A1, CYP27A1 and CYP7B1), as well as those of associated nuclear receptors (LXRα, FXR, PPARα, and SREBP 2). In addition, mRNA levels of other enzymes of interest were measured (ACAT 2, as well as HMGCoA Reductase and HMGCoA Synthase). The gene expression study was completed with SRB1 and LDLr, apolipoproteins A1 and B and membrane transporters ABC A1, ABC G5. The major effect induced by a low level of DU contamination in apo-E deficient mice was a decrease in hepatic gene expression of the enzyme CYP7B1 (-23%) and nuclear

  16. Polioencephalomalacia and Heart Failure Secondary to Presumptive Thiamine Deficiency, Hepatic Lipidosis, and Starvation in 2 Abandoned Siamese Cats.

    Science.gov (United States)

    Anholt, H; Himsworth, C; Britton, A

    2016-07-01

    Two 4-year-old spayed female Siamese cats were seized by the British Columbia Society for the Prevention of Cruelty to Animals after confinement to an abandoned housing unit without food for 9 weeks. One cat was found dead, and the second was euthanized within 24 hours due to neurologic deterioration despite therapy. Polioencephalomalacia of the caudal colliculus, hepatic lipidosis, cachexia, and congestive heart failure with cardiomyocyte atrophy were identified in both cats through postmortem examination and attributed to a prolonged period of starvation. Brain lesions were likely the result of thiamine deficiency (Chastek paralysis), which can be associated with both malnutrition and liver disease. This case highlights the importance of thiamine supplementation during realimentation of cats with hepatic lipidosis. Heart failure resulting from cachexia may have contributed to the death of the first cat and the morbidity of the second cat. © The Author(s) 2016.

  17. Mcph1-deficient mice reveal a role for MCPH1 in otitis media.

    Directory of Open Access Journals (Sweden)

    Jing Chen

    Full Text Available Otitis media is a common reason for hearing loss, especially in children. Otitis media is a multifactorial disease and environmental factors, anatomic dysmorphology and genetic predisposition can all contribute to its pathogenesis. However, the reasons for the variable susceptibility to otitis media are elusive. MCPH1 mutations cause primary microcephaly in humans. So far, no hearing impairment has been reported either in the MCPH1 patients or mouse models with Mcph1 deficiency. In this study, Mcph1-deficient (Mcph1(tm1a (/tm1a mice were produced using embryonic stem cells with a targeted mutation by the Sanger Institute's Mouse Genetics Project. Auditory brainstem response measurements revealed that Mcph1(tm1a (/tm1a mice had mild to moderate hearing impairment with around 70% penetrance. We found otitis media with effusion in the hearing-impaired Mcph1(tm1a (/tm1a mice by anatomic and histological examinations. Expression of Mcph1 in the epithelial cells of middle ear cavities supported its involvement in the development of otitis media. Other defects of Mcph1(tm1a (/tm1a mice included small skull sizes, increased micronuclei in red blood cells, increased B cells and ocular abnormalities. These findings not only recapitulated the defects found in other Mcph1-deficient mice or MCPH1 patients, but also revealed an unexpected phenotype, otitis media with hearing impairment, which suggests Mcph1 is a new gene underlying genetic predisposition to otitis media.

  18. Association between vitamin D deficiency and pre-existing resistance-associated hepatitis C virus NS5A variants.

    Science.gov (United States)

    Okubo, Tomomi; Atsukawa, Masanori; Tsubota, Akihito; Shimada, Noritomo; Abe, Hiroshi; Yoshizawa, Kai; Arai, Taeang; Nakagawa, Ai; Itokawa, Norio; Kondo, Chisa; Aizawa, Yoshio; Iwakiri, Katsuhiko

    2017-06-01

    Although interferon-free therapy with direct-acting antivirals has developed as a standard of care for chronic hepatitis C, the existence of resistance-associated variants (RAVs) has a negative impact on treatment results. Recently, several studies indicated a relationship between chronic hepatitis C and serum vitamin D levels. However, the relationship between RAVs at the hepatitis C virus non-structure 5A (NS5A) region and serum vitamin D level has not yet been examined. Among patients with genotype 1 chronic hepatitis C who were enrolled in a multicenter cooperative study, our subjects comprised 247 patients in whom it was possible to measure RAVs at the NS5A region. These RAVs were measured using a direct sequencing method. The median age of patients was 70 years (range, 24-87 years), and the number of female patients was 135 (54.7%). The median serum 25(OH) D3 level was 22 ng/mL (range, 6-64 ng/mL). L31 and Y93 RAVs at the NS5A region were detected in 3.7% (9/247) and 13.4% (33/247) of patients, respectively. Multivariate analysis identified vitamin D deficiency (serum 25(OH) D3 ≤ 20 ng/mL) (P = 5.91 × 10⁻ 5 , odds ratio = 5.015) and elderly age (>70 years) (P = 1.85 × 10 -3 , odds ratio = 3.364) as contributing independent factors associated with the presence of the L31 and/or Y93 RAVs. The Y93H RAV was detected in 25.9% (29/112) of patients with a vitamin D deficiency, and in 8.9% (12/135) of those with a serum 25(OH) D3 level >20 ng/mL (P = 4.90 × 10 -3 ). We showed that RAVs at the NS5A region are associated with vitamin D deficiency and elderly age, which may have a negative influence on innate/adaptive immune responses to hepatitis C virus infection. © 2016 The Japan Society of Hepatology.

  19. Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

    Directory of Open Access Journals (Sweden)

    Tongfang Tang

    Full Text Available BACKGROUND: Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD through alternation of liver innate immune response. AIMS: The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. METHODS: Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. RESULTS: High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4 expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. CONCLUSION: High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

  20. Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

    Science.gov (United States)

    Tang, Tongfang; Sui, Yongheng; Lian, Min; Li, Zhiping; Hua, Jing

    2013-01-01

    Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response. The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

  1. Phenolic Profiling of Caffeic Acid O-Methyltransferase-Deficient Poplar Reveals Novel Benzodioxane Oligolignols1

    Science.gov (United States)

    Morreel, Kris; Ralph, John; Lu, Fachuang; Goeminne, Geert; Busson, Roger; Herdewijn, Piet; Goeman, Jan L.; Van der Eycken, Johan; Boerjan, Wout; Messens, Eric

    2004-01-01

    Caffeic acid O-methyltransferase (COMT) catalyzes preferentially the methylation of 5-hydroxyconiferaldehyde to sinapaldehyde in monolignol biosynthesis. Here, we have compared HPLC profiles of the methanol-soluble phenolics fraction of xylem tissue from COMT-deficient and control poplars (Populus spp.), using statistical analysis of the peak heights. COMT down-regulation results in significant concentration differences for 25 of the 91 analyzed peaks. Eight peaks were exclusively detected in COMT-deficient poplar, of which four could be purified for further identification using mass spectrometry/mass spectrometry, nuclear magnetic resonance, and spiking of synthesized reference compounds. These new compounds were derived from 5-hydroxyconiferyl alcohol or 5-hydroxyconiferaldehyde and were characterized by benzodioxane moieties, a structural type that is also increased in the lignins of COMT-deficient plants. One of these four benzodioxanes amounted to the most abundant oligolignol in the HPLC profile. Furthermore, all of the differentially accumulating oligolignols involving sinapyl units were either reduced in abundance or undetectable. The concentration levels of all identified oligolignols were in agreement with the relative supply of monolignols and with their chemical coupling propensities, which supports the random coupling hypothesis. Chiral HPLC analysis of the most abundant benzodioxane dimer revealed the presence of both enantiomers in equal amounts, indicating that they were formed by radical coupling reactions under simple chemical control rather than guided by dirigent proteins. PMID:15563622

  2. Phenolic profiling of caffeic acid O-methyltransferase-deficient poplar reveals novel benzodioxane oligolignols.

    Science.gov (United States)

    Morreel, Kris; Ralph, John; Lu, Fachuang; Goeminne, Geert; Busson, Roger; Herdewijn, Piet; Goeman, Jan L; Van der Eycken, Johan; Boerjan, Wout; Messens, Eric

    2004-12-01

    Caffeic acid O-methyltransferase (COMT) catalyzes preferentially the methylation of 5-hydroxyconiferaldehyde to sinapaldehyde in monolignol biosynthesis. Here, we have compared HPLC profiles of the methanol-soluble phenolics fraction of xylem tissue from COMT-deficient and control poplars (Populus spp.), using statistical analysis of the peak heights. COMT down-regulation results in significant concentration differences for 25 of the 91 analyzed peaks. Eight peaks were exclusively detected in COMT-deficient poplar, of which four could be purified for further identification using mass spectrometry/mass spectrometry, nuclear magnetic resonance, and spiking of synthesized reference compounds. These new compounds were derived from 5-hydroxyconiferyl alcohol or 5-hydroxyconiferaldehyde and were characterized by benzodioxane moieties, a structural type that is also increased in the lignins of COMT-deficient plants. One of these four benzodioxanes amounted to the most abundant oligolignol in the HPLC profile. Furthermore, all of the differentially accumulating oligolignols involving sinapyl units were either reduced in abundance or undetectable. The concentration levels of all identified oligolignols were in agreement with the relative supply of monolignols and with their chemical coupling propensities, which supports the random coupling hypothesis. Chiral HPLC analysis of the most abundant benzodioxane dimer revealed the presence of both enantiomers in equal amounts, indicating that they were formed by radical coupling reactions under simple chemical control rather than guided by dirigent proteins.

  3. A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies.

    Directory of Open Access Journals (Sweden)

    Masakazu Kohda

    2016-01-01

    Full Text Available Mitochondrial disorders have the highest incidence among congenital metabolic disorders characterized by biochemical respiratory chain complex deficiencies. It occurs at a rate of 1 in 5,000 births, and has phenotypic and genetic heterogeneity. Mutations in about 1,500 nuclear encoded mitochondrial proteins may cause mitochondrial dysfunction of energy production and mitochondrial disorders. More than 250 genes that cause mitochondrial disorders have been reported to date. However exact genetic diagnosis for patients still remained largely unknown. To reveal this heterogeneity, we performed comprehensive genomic analyses for 142 patients with childhood-onset mitochondrial respiratory chain complex deficiencies. The approach includes whole mtDNA and exome analyses using high-throughput sequencing, and chromosomal aberration analyses using high-density oligonucleotide arrays. We identified 37 novel mutations in known mitochondrial disease genes and 3 mitochondria-related genes (MRPS23, QRSL1, and PNPLA4 as novel causative genes. We also identified 2 genes known to cause monogenic diseases (MECP2 and TNNI3 and 3 chromosomal aberrations (6q24.3-q25.1, 17p12, and 22q11.21 as causes in this cohort. Our approaches enhance the ability to identify pathogenic gene mutations in patients with biochemically defined mitochondrial respiratory chain complex deficiencies in clinical settings. They also underscore clinical and genetic heterogeneity and will improve patient care of this complex disorder.

  4. Peculiarities of the free radical processes in rat liver mitochondria under toxic hepatitis on the background of alimentary protein deficiency

    Directory of Open Access Journals (Sweden)

    G. P. Kopylchuk

    2016-04-01

    Full Text Available The rate of superoxide anion radical, hydroxyl radical and hydrogen peroxide generation, the level of oxidative modification of mitochondrial proteins in the liver of rats with toxic hepatitis was investigated on the background of alimentary protein deficiency. We did not find significant increases of the intensity of free radical processes in liver mitochondria of rats maintained on the protein-deficient ration. The most significant intensification of free radical processes in liver mitochondria is observed under the conditions of toxic hepatitis, induced on the background of alimentary protein deprivation. Under these conditions the aggravation of all studied forms of reactive oxygen species generation was observed in liver mitochondria. The generation rates were increased as follows: O2 – by 1.7 times, Н2О2 – by 1.5 times, •ОН – practically double on the background of accumulation of oxidized mitochondria-derived proteins. The established changes in thiol groups’ redox status of respiratory chain proteins insoluble in 0.05 M sodium-phosphate buffer (pH 11.5, and changes of their carbonyl derivatives content may be considered as one of the regulatory factors of mitochondrial energy-generating function.

  5. Epigallocatechin-3-gallate enhances key enzymatic activities of hepatic thioredoxin and glutathione systems in selenium-optimal mice but activates hepatic Nrf2 responses in selenium-deficient mice

    Directory of Open Access Journals (Sweden)

    Ruixia Dong

    2016-12-01

    Full Text Available Selenium participates in the antioxidant defense mainly through a class of selenoproteins, including thioredoxin reductase. Epigallocatechin-3-gallate (EGCG is the most abundant and biologically active catechin in green tea. Depending upon the dose and biological systems, EGCG may function either as an antioxidant or as an inducer of antioxidant defense via its pro-oxidant action or other unidentified mechanisms. By manipulating the selenium status, the present study investigated the interactions of EGCG with antioxidant defense systems including the thioredoxin system comprising of thioredoxin and thioredoxin reductase, the glutathione system comprising of glutathione and glutathione reductase coupled with glutaredoxin, and the Nrf2 system. In selenium-optimal mice, EGCG increased hepatic activities of thioredoxin reductase, glutathione reductase and glutaredoxin. These effects of EGCG appeared to be not due to overt pro-oxidant action because melatonin, a powerful antioxidant, did not influence the increase. However, in selenium-deficient mice, with low basal levels of thioredoxin reductase 1, the same dose of EGCG did not elevate the above-mentioned enzymes; intriguingly EGCG in turn activated hepatic Nrf2 response, leading to increased heme oxygenase 1 and NAD(PH:quinone oxidoreductase 1 protein levels and thioredoxin activity. Overall, the present work reveals that EGCG is a robust inducer of the Nrf2 system only in selenium-deficient conditions. Under normal physiological conditions, in selenium-optimal mice, thioredoxin and glutathione systems serve as the first line defense systems against the stress induced by high doses of EGCG, sparing the activation of the Nrf2 system.

  6. Hepatic deficiency of the pioneer transcription factor FoxA restricts hepatitis B virus biosynthesis by the developmental regulation of viral DNA methylation.

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    Vanessa C McFadden

    2017-02-01

    Full Text Available The FoxA family of pioneer transcription factors regulates hepatitis B virus (HBV transcription, and hence viral replication. Hepatocyte-specific FoxA-deficiency in the HBV transgenic mouse model of chronic infection prevents the transcription of the viral DNA genome as a result of the failure of the developmentally controlled conversion of 5-methylcytosine residues to cytosine during postnatal hepatic maturation. These observations suggest that pioneer transcription factors such as FoxA, which mark genes for expression at subsequent developmental steps in the cellular differentiation program, mediate their effects by reversing the DNA methylation status of their target genes to permit their ensuing expression when the appropriate tissue-specific transcription factor combinations arise during development. Furthermore, as the FoxA-deficient HBV transgenic mice are viable, the specific developmental timing, abundance and isoform type of pioneer factor expression must permit all essential liver gene expression to occur at a level sufficient to support adequate liver function. This implies that pioneer transcription factors can recognize and mark their target genes in distinct developmental manners dependent upon, at least in part, the concentration and affinity of FoxA for its binding sites within enhancer and promoter regulatory sequence elements. This selective marking of cellular genes for expression by the FoxA pioneer factor compared to HBV may offer the opportunity for the specific silencing of HBV gene expression and hence the resolution of chronic HBV infections which are responsible for approximately one million deaths worldwide annually due to liver cirrhosis and hepatocellular carcinoma.

  7. Hepatic tissue environment in NEMO-deficient mice critically regulates positive selection of donor cells after hepatocyte transplantation.

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    Michaela Kaldenbach

    Full Text Available BACKGROUND: Hepatocyte transplantation (HT is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. METHODS: Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa. RESULTS: Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. CONCLUSION: This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and

  8. Averrhoa carambola free phenolic extract ameliorates nonalcoholic hepatic steatosis by modulating mircoRNA-34a, mircoRNA-33 and AMPK pathways in leptin receptor-deficient db/db mice.

    Science.gov (United States)

    Pang, Daorui; You, Lijun; Zhou, Lin; Li, Tong; Zheng, Bisheng; Liu, Rui Hai

    2017-12-13

    The objective of the present study is to investigate the hepatic steatosis relieving effect of Averrhoa carambola free phenolic extract (ACF) on leptin receptor-deficient (db/db) mice and elucidate the modulation hepatic lipogenesis mechanisms. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) assays, accompanying hematoxylin and eosin (H&E) staining, were applied to identify the alleviation of liver histopathological changes. Serum and hepatic lipid assays, combined with oil red O staining, were used to investigate the amelioration of lipid accumulation. Further assessments by quantitative real-time PCR and western blot assays were used to elucidate the suppression of the fatty acid and triglyceride (TG) synthesis mechanisms underlying ACF protection. These results indicated that ACF treatment significantly reduced the liver TG of db/db mice (p < 0.05). The mechanisms are partly through phosphorylation of AMPK α and down-regulation of SREBP-1c expression, and further down-regulation of FAS and SCD1 (p < 0.05). In addition, the expression levels of mircoRNA-34a and mircoRNA-33, which modulate this signaling pathway, were significantly down-regulated by ACF treatment (p < 0.05). Collectively, these results revealed that ACF exhibited a potent hepatic steatosis relieving effect partly by inhibiting the signal transduction of hepatic lipogenesis.

  9. ARGINASE 2 DEFICIENCY RESULTS IN SPONTANEOUS STEATOHEPATITIS: A NOVEL LINK BETWEEN INNATE IMMUNE ACTIVATION AND HEPATIC DE NOVO LIPOGENESIS

    Science.gov (United States)

    Navarro, Laura A.; Wree, Alexander; Povero, Davide; Berk, Michael P.; Eguchi, Akiko; Ghosh, Sudakshina; Papouchado, Bettina G.; Erzurum, Serpil C.; Feldstein, Ariel E.

    2016-01-01

    BACKGROUND & AIMS Innate immune activation has been postulated as a central mechanism for disease progression from hepatic steatosis to steatohepatitis in obesity-related fatty liver disease. Arginase 2 competes with inducible nitric oxide synthase (iNOS) for its substrate and the balance between these two enzymes plays a crucial role in regulating immune responses and macrophage activation. Our aim was to test the hypothesis that arginase 2 deficiency in mice favors progression from isolated hepatic steatosis, induced by high fat feeding to steatohepatitis. METHODS Arginase 2-knockout (Arg2−/−) mice were studied for changes in liver histology and metabolic phenotype at baseline and after a short term course (7 week) feeding with a high fat (HFAT) diet. In additional experiments, Arg2−/− mice received tail vein injections of liposome-encapsulated clodronate (CLOD) over a three-week period to selectively deplete liver macrophages. RESULTS Unexpectedly, Arg2−/− mice showed profound changes in their livers at baseline characterized by significant steatosis as demonstrated with histological and biochemical analysis. These changes were independent of systemic metabolic parameters and associated with marked increase mRNA levels of genes involved in hepatic de novo lipogenesis. Liver injury and inflammation were present with elevated serum ALT, marked infiltration of F4/80 positive cells, and increased mRNA levels of inflammatory genes. HFAT feeding exacerbated these changes. Macrophage depletion after CLOD injection significantly attenuated lipid deposition and normalized lipogenic mRNA profile of livers from Arg2−/− mice. CONCLUSIONS This study identifies arginase 2 as novel link between innate immune responses, hepatic lipid deposition, and liver injury. PMID:25234945

  10. Effect of dietary fat on hepatic liver X receptor expression in P-glycoprotein deficient mice: implications for cholesterol metabolism

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    Lee Stephen D

    2008-06-01

    Full Text Available Abstract Pgp (P-glycoprotein, MDR1, ABCB1 is an energy-dependent drug efflux pump that is a member of the ATP-binding cassette (ABC family of proteins. Preliminary studies have reported that nonspecific inhibitors of Pgp affect synthesis and esterification of cholesterol, putatively by blocking trafficking of cholesterol from the plasma membrane to the endoplasmic reticulum, and that relative increases in Pgp within a given cell type are associated with increased accumulation of cholesterol. Several key efflux proteins involved in the cholesterol metabolic pathway are transcriptionally regulated by the nuclear hormone liver X receptor (LXR. Therefore, to examine the interplay between P-glycoprotein and the cholesterol metabolic pathway, we utilized a high fat, normal cholesterol diet to upregulate LXRα without affecting dietary cholesterol. Our research has demonstrated that mice lacking in P-glycoprotein do not exhibit alterations in hepatic total cholesterol storage, circulating plasma total cholesterol levels, or total cholesterol concentration in the bile when compared to control animals on either a normal (25% calories from dietary fat or high fat (45% calories from dietary fat diet. However, p-glycoprotein deficient mice (Mdr1a-/-/1b-/- exhibit increased hepatic LXRα protein expression and an elevation in fecal cholesterol concentration when compared to controls.

  11. Ontogeny of hepatic energy metabolism genes in mice as revealed by RNA-sequencing.

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    Helen J Renaud

    Full Text Available The liver plays a central role in metabolic homeostasis by coordinating synthesis, storage, breakdown, and redistribution of nutrients. Hepatic energy metabolism is dynamically regulated throughout different life stages due to different demands for energy during growth and development. However, changes in gene expression patterns throughout ontogeny for factors important in hepatic energy metabolism are not well understood. We performed detailed transcript analysis of energy metabolism genes during various stages of liver development in mice. Livers from male C57BL/6J mice were collected at twelve ages, including perinatal and postnatal time points (n = 3/age. The mRNA was quantified by RNA-Sequencing, with transcript abundance estimated by Cufflinks. One thousand sixty energy metabolism genes were examined; 794 were above detection, of which 627 were significantly changed during at least one developmental age compared to adult liver. Two-way hierarchical clustering revealed three major clusters dependent on age: GD17.5-Day 5 (perinatal-enriched, Day 10-Day 20 (pre-weaning-enriched, and Day 25-Day 60 (adolescence/adulthood-enriched. Clustering analysis of cumulative mRNA expression values for individual pathways of energy metabolism revealed three patterns of enrichment: glycolysis, ketogenesis, and glycogenesis were all perinatally-enriched; glycogenolysis was the only pathway enriched during pre-weaning ages; whereas lipid droplet metabolism, cholesterol and bile acid metabolism, gluconeogenesis, and lipid metabolism were all enriched in adolescence/adulthood. This study reveals novel findings such as the divergent expression of the fatty acid β-oxidation enzymes Acyl-CoA oxidase 1 and Carnitine palmitoyltransferase 1a, indicating a switch from mitochondrial to peroxisomal β-oxidation after weaning; as well as the dynamic ontogeny of genes implicated in obesity such as Stearoyl-CoA desaturase 1 and Elongation of very long chain fatty

  12. Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion.

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    Boedeker, J C; Doolittle, M H; White, A L

    2001-11-01

    Combined lipase deficiency (cld) is a recessively inherited disorder in mice associated with a deficiency of LPL and hepatic lipase (HL) activity. LPL is synthesized in cld tissues but is retained in the endoplasmic reticulum (ER), whereas mouse HL (mHL) is secreted but inactive. In this study we investigated the effect of cld on the secretion of human HL (hHL) protein mass and activity. Differentiated liver cell lines were derived from cld mice and their normal heterozygous (het) littermates by transformation of hepatocytes with SV40 large T antigen. After transient transfection with lipase expression constructs, secretion of hLPL activity from cld cells was only 12% of that from het cells. In contrast, the rate of secretion of hHL activity and protein mass per unit of expressed hHL mRNA was identical for the two cell lines. An intermediate effect was observed for mHL, with a 46% reduction in secretion of activity from cld cells. The ER glucosidase inhibitor, castanospermine, decreased secretion of both hLPL and hHL from het cells by approximately 70%, but by only approximately 45% from cld cells. This is consistent with data suggesting that cld may result from a reduced concentration of the ER chaperone calnexin. In conclusion, our results demonstrate a differential effect of cld on hLPL, mHL, and hHL secretion, suggesting differential requirements for activation and exit of the enzymes from the ER.

  13. Proteins Differentially Expressed in the Pancreas of Hepatic Alcohol Dehydrogenase-Deficient Deer Mice Fed Ethanol For 3 Months.

    Science.gov (United States)

    Bhopale, Kamlesh K; Amer, Samir M; Kaphalia, Lata; Soman, Kizhake V; Wiktorowicz, John E; Shakeel Ansari, Ghulam A; Kaphalia, Bhupendra S

    2017-07-01

    The aim of this study was to identify differentially expressed proteins in the pancreatic tissue of hepatic alcohol dehydrogenase-deficient deer mice fed ethanol to understand metabolic basis and mechanism of alcoholic chronic pancreatitis. Mice were fed liquid diet containing 3.5 g% ethanol daily for 3 months, and differentially expressed pancreatic proteins were identified by protein separation using 2-dimensional gel electrophoresis and identification by mass spectrometry. Nineteen differentially expressed proteins were identified by applying criteria established for protein identification in proteomics. An increased abundance was found for ribosome-binding protein 1, 60S ribosomal protein L31-like isoform 1, histone 4, calcium, and adenosine triphosphate (ATP) binding proteins and the proteins involved in antiapoptotic processes and endoplasmic reticulum function, stress, and/or homeostasis. Low abundance was found for endoA cytokeratin, 40S ribosomal protein SA, amylase 2b isoform precursor, serum albumin, and ATP synthase subunit β and the proteins involved in cell motility, structure, and conformation. Chronic ethanol feeding in alcohol dehydrogenase-deficient deer mice differentially expresses pancreatic functional and structural proteins, which can be used to develop biomarker(s) of alcoholic chronic pancreatitis, particularly amylase 2b precursor, and 60 kDa heat shock protein and those involved in ATP synthesis and blood osmotic pressure.

  14. Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion

    NARCIS (Netherlands)

    Diepen, J.A. van; Stienstra, R.; Vroegrijk, I.O.C.M.; Berg, S.A.A. van den; Salvatori, D.; Hooiveld, G.J.; Kersten, S.; Tack, C.J.; Netea, M.G.; Smit, J.W.A.; Joosten, L.A.B.; Havekes, L.M.; Dijk, K.W. van; Rensen, P.C.N.

    2013-01-01

    Caspase-1 is known to activate the proinflammatory cytokines IL-1β and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by

  15. Caspase-1 deficiency reduces intestinal and hepatic triglyceride-rich lipoprotein secretion

    NARCIS (Netherlands)

    Diepen, van Janna A.; Stienstra, Rinke; Hooiveld, Guido; Willems van Dijk, Ko; Rensen, Patrick C.

    2013-01-01

    Background and Aims: Inflammasome-mediated caspase-1 activity regulates the maturation and release of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-18. Recently, we showed that caspase-1 deficiency strongly reduces high fat diet-induced adiposity although the mechanism is still unclear.

  16. Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.

    Science.gov (United States)

    Wang, Xiangxi; Zhu, Ling; Dang, Minghao; Hu, Zhongyu; Gao, Qiang; Yuan, Shuai; Sun, Yao; Zhang, Bo; Ren, Jingshan; Kotecha, Abhay; Walter, Thomas S; Wang, Junzhi; Fry, Elizabeth E; Stuart, David I; Rao, Zihe

    2017-01-24

    Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention.

  17. Comparison of vitamin D deficiency and magnitude of severity of vitamin D deficiency in cirrhotic and non-cirrhotic patients with chronic hepatitis C in a tertiary care hospital Rawalpindi, Pakistan

    International Nuclear Information System (INIS)

    Hamid, S.; Faheem, M.; Ambreen, S.; Tirmizi, A.; Umar, M.

    2017-01-01

    Objective: To determine Vitamin D deficiency in both cirrhotic and non-cirrhotic patients with chronic hepatitis C (CHC). Methodology: We conducted a cross-sectional study at Centre for Liver and Digestive Diseases (CLD), Holy Family Hospital, Rawalpindi, Pakistan from August 2015 to February 2016 and included 120 Patients with CHC with or without cirrhosis. Two groups were formed and vitamin D levels were measured and level of severity was assessed. Results: Out of 120 patients, 94(78.3%) patients had Vitamin D deficiency. 63(100%) cirrhotic patients and 31 54.4%) non cirrhotic patients had Vitamin D deficiency. In cirrhotic patients, 26(41.3%) had mild and 36(58.7%) had moderate Vitamin D deficiency while in non-cirrhotic patients 25(43.9%) had mild and 6(10.5%) had moderate deficiency. No patient with severe Vitamin D deficiency was observed. Conclusion: Most of the patients infected with CHC suffer from vitamin D deficiency. This was observed more in cirrhotic patients than non-cirrhotic patients. Moreover, positive correlation was observed among vitamin D deficiency and stage of fibrosis. (author)

  18. Redetermination of AgNb2PS10 revealing a silver deficiency

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    Hoseop Yun

    2009-08-01

    Full Text Available In comparison with a previous crystallographic study [Goh et al. (2002. J. Solid State Chem. 168, 119–125] of the title compound, silver diniobium tris(disulfide tetrathiophosphate(V, that reports a full occupation of the silver position and isotropic displacement parameters for the atoms, the current redetermination reveals a silver deficiency with a site-occupation factor of 0.88 (1 and reports all atoms with anisotropic displacement parameters. The structure of Ag0.88Nb2PS10 is composed of ∞1[Nb2PS10] chains, which are built up from pairs of distorted bicapped trigonal-prismatic [NbS8] polyhedra forming [Nb2S12] dimers and of tetrahedral [PS4] groups. These chains are connected via the statistically disordered Ag+ ions, forming double layers. Adjacent layers are stacked solely through van der Waals forces into a three-dimensional structure. Short and long Nb—Nb distances [2.880 (1 and 3.770 (2 Å, respectively] alternate along the chain and S22− and S2− anionic species are observed.

  19. Relationship between vitamin A deficiency and the thyroid axis in clinically stable patients with liver cirrhosis related to hepatitis C virus.

    Science.gov (United States)

    El-Eshmawy, Mervat M; Arafa, Mona M; Elzehery, Rasha R; Elhelaly, Rania M; Elrakhawy, Mohamed M; El-Baiomy, Azza A

    2016-09-01

    Vitamin A deficiency (VAD) and altered thyroid function are commonly encountered in patients with liver cirrhosis. The link between vitamin A metabolism and thyroid function has been previously identified. The aim of this study was to explore the association between VAD and the thyroid axis in clinically stable patients with cirrhosis related to hepatitis C virus (HCV). One hundred and twelve patients with clinically stable HCV-related cirrhosis and 56 healthy controls matched for age, sex, and socioeconomic status were recruited for this study. Vitamin A status, liver function, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), reverse triiodothyronine (rT3), anti-thyroid peroxidase antibodies (anti-TPO), and thyroid volume were evaluated. The prevalence of VAD among patients with HCV-related cirrhosis was 62.5% compared with 5.4% among controls (P vitamin A status: VAD and normal vitamin A. Patients with VAD had significantly lower vitamin A intake and serum albumin and higher serum bilirubin, FT4, FT3, and TSH than patients with normal vitamin A status. Multiple logistic regression analysis revealed that VAD was associated with Child-Pugh score (β = 0.11, P = 0.05) and TSH (β = -1.63, P = 0.02) independently of confounding variables. We conclude that VAD may be linked to central hyperthyroidism in patients with clinically stable HCV-related liver cirrhosis.

  20. de Toni-Fanconi-Debré syndrome with Leigh syndrome revealing severe muscle cytochrome c oxidase deficiency

    NARCIS (Netherlands)

    Ogier, H.; Lombes, A.; Scholte, H. R.; Poll-The, B. T.; Fardeau, M.; Alcardi, J.; Vignes, B.; Niaudet, P.; Saudubray, J. M.

    1988-01-01

    We describe a patient with severe muscle cytochrome c oxidase deficiency who had de Toni-Fanconi-Debré syndrome and acute neurologic deterioration resembling Leigh syndrome, without clear evidence of muscle abnormality. Metabolic investigations revealed elevated cerebrospinal fluid lactate values

  1. Evolution of hepatic glucose metabolism: liver-specific glucokinase deficiency explained by parallel loss of the gene for glucokinase regulatory protein (GCKR.

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    Zhao Yang Wang

    Full Text Available Glucokinase (GCK plays an important role in the regulation of carbohydrate metabolism. In the liver, phosphorylation of glucose to glucose-6-phosphate by GCK is the first step for both glycolysis and glycogen synthesis. However, some vertebrate species are deficient in GCK activity in the liver, despite containing GCK genes that appear to be compatible with function in their genomes. Glucokinase regulatory protein (GCKR is the most important post-transcriptional regulator of GCK in the liver; it participates in the modulation of GCK activity and location depending upon changes in glucose levels. In experimental models, loss of GCKR has been shown to associate with reduced hepatic GCK protein levels and activity.GCKR genes and GCKR-like sequences were identified in the genomes of all vertebrate species with available genome sequences. The coding sequences of GCKR and GCKR-like genes were identified and aligned; base changes likely to disrupt coding potential or splicing were also identified.GCKR genes could not be found in the genomes of 9 vertebrate species, including all birds. In addition, in multiple mammalian genomes, whereas GCKR-like gene sequences could be identified, these genes could not predict a functional protein. Vertebrate species that were previously reported to be deficient in hepatic GCK activity were found to have deleted (birds and lizard or mutated (mammals GCKR genes. Our results suggest that mutation of the GCKR gene leads to hepatic GCK deficiency due to the loss of the stabilizing effect of GCKR.

  2. A methionine-choline-deficient diet elicits NASH in the immunodeficient mouse featuring a model for hepatic cell transplantation.

    Science.gov (United States)

    Pelz, Sandra; Stock, Peggy; Brückner, Sandra; Christ, Bruno

    2012-02-01

    Non-alcoholic staetohepatitis (NASH) is associated with fat deposition in the liver favoring inflammatory processes and development of fibrosis, cirrhosis and finally hepatocellular cancer. In Western lifestyle countries, NASH has reached a 20% prevalence in the obese population with escalating tendency in the future. Very often, liver transplantation is the only therapeutic option. Recently, transplantation of hepatocyte-like cells differentiated from mesenchymal stem cells was suggested a feasible alternative to whole organ transplantation to ameliorate donor organ shortage. Hence, in the present work an animal model of NASH was established in immunodeficient mice to investigate the feasibility of human stem cell-derived hepatocyte-like cell transplantation. NASH was induced by feeding a methionine/choline-deficient diet (MCD-diet) for up to 5 weeks. Animals developed a fatty liver featuring fibrosis and elevation of the proinflammatory markers serum amyloid A (SAA) and tumor necrosis factor alpha (TNFα). Hepatic triglycerides were significantly increased as well as alanine aminotransferase demonstrating inflammation-linked hepatocyte damage. Elevation of αSMA mRNA and collagen I as well as liver architecture deterioation indicated massive fibrosis. Both short- and long-term post-transplantation human hepatocyte-like cells resided in the mouse host liver indicating parenchymal penetration and most likely functional engraftment. Hence, the NASH model in the immunodeficient mouse is the first to allow for the assessment of the therapeutic impact of human stem cell-derived hepatocyte transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing

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    Dev, Jyoti; Brüschweiler, Sven [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States); Ouyang, Bo [Chinese Academy of Sciences, State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology (China); Chou, James J., E-mail: james-chou@hms.harvard.edu [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States)

    2015-04-15

    The p7 membrane protein encoded by hepatitis C virus (HCV) assembles into a homo-hexamer that selectively conducts cations. An earlier solution NMR structure of the hexameric complex revealed a funnel-like architecture and suggests that a ring of conserved asparagines near the narrow end of the funnel are important for cation interaction. NMR based drug-binding experiments also suggest that rimantadine can allosterically inhibit ion conduction via a molecular wedge mechanism. These results suggest the presence of dilation and contraction of the funnel tip that are important for channel activity and that the action of the drug is attenuating this motion. Here, we determined the conformational dynamics and solvent accessibility of the p7 channel. The proton exchange measurements show that the cavity-lining residues are largely water accessible, consistent with the overall funnel shape of the channel. Our relaxation dispersion data show that residues Val7 and Leu8 near the asparagine ring are subject to large chemical exchange, suggesting significant intrinsic channel breathing at the tip of the funnel. Moreover, the hinge regions connecting the narrow and wide regions of the funnel show strong relaxation dispersion and these regions are the binding sites for rimantadine. Presence of rimantadine decreases the conformational dynamics near the asparagine ring and the hinge area. Our data provide direct observation of μs–ms dynamics of the p7 channel and support the molecular wedge mechanism of rimantadine inhibition of the HCV p7 channel.

  4. Neolithic and Medieval virus genomes reveal complex evolution of Hepatitis B.

    Science.gov (United States)

    Krause-Kyora, Ben; Susat, Julian; Key, Felix M; Kühnert, Denise; Bosse, Esther; Immel, Alexander; Rinne, Christoph; Kornell, Sabin-Christin; Yepes, Diego; Franzenburg, Sören; Heyne, Henrike O; Meier, Thomas; Lösch, Sandra; Meller, Harald; Friederich, Susanne; Nicklisch, Nicole; Alt, Kurt W; Schreiber, Stefan; Tholey, Andreas; Herbig, Alexander; Nebel, Almut; Krause, Johannes

    2018-05-10

    The hepatitis B virus (HBV) is one of the most widespread human pathogens known today, yet its origin and evolutionary history are still unclear and controversial. Here, we report the analysis of three ancient HBV genomes recovered from human skeletons found at three different archaeological sites in Germany. We reconstructed two Neolithic and one medieval HBV genomes by de novo assembly from shotgun DNA sequencing data. Additionally, we observed HBV-specific peptides using paleo-proteomics. Our results show that HBV circulates in the European population for at least 7000 years. The Neolithic HBV genomes show a high genomic similarity to each other. In a phylogenetic network, they do not group with any human-associated HBV genome and are most closely related to those infecting African non-human primates. These ancient virus forms appear to represent distinct lineages that have no close relatives today and possibly went extinct. Our results reveal the great potential of ancient DNA from human skeletons in order to study the long-time evolution of blood borne viruses. © 2018, Krause-Kyora et al.

  5. Transverse relaxation dispersion of the p7 membrane channel from hepatitis C virus reveals conformational breathing

    International Nuclear Information System (INIS)

    Dev, Jyoti; Brüschweiler, Sven; Ouyang, Bo; Chou, James J.

    2015-01-01

    The p7 membrane protein encoded by hepatitis C virus (HCV) assembles into a homo-hexamer that selectively conducts cations. An earlier solution NMR structure of the hexameric complex revealed a funnel-like architecture and suggests that a ring of conserved asparagines near the narrow end of the funnel are important for cation interaction. NMR based drug-binding experiments also suggest that rimantadine can allosterically inhibit ion conduction via a molecular wedge mechanism. These results suggest the presence of dilation and contraction of the funnel tip that are important for channel activity and that the action of the drug is attenuating this motion. Here, we determined the conformational dynamics and solvent accessibility of the p7 channel. The proton exchange measurements show that the cavity-lining residues are largely water accessible, consistent with the overall funnel shape of the channel. Our relaxation dispersion data show that residues Val7 and Leu8 near the asparagine ring are subject to large chemical exchange, suggesting significant intrinsic channel breathing at the tip of the funnel. Moreover, the hinge regions connecting the narrow and wide regions of the funnel show strong relaxation dispersion and these regions are the binding sites for rimantadine. Presence of rimantadine decreases the conformational dynamics near the asparagine ring and the hinge area. Our data provide direct observation of μs–ms dynamics of the p7 channel and support the molecular wedge mechanism of rimantadine inhibition of the HCV p7 channel

  6. Diagnosis of adenylosuccinate lyase deficiency by metabolomic profiling in plasma reveals a phenotypic spectrum

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    Taraka R. Donti

    2016-09-01

    Full Text Available Adenylosuccinate lyase (ADSL deficiency is a rare autosomal recessive neurometabolic disorder that presents with a broad-spectrum of neurological and physiological symptoms. The ADSL gene produces an enzyme with binary molecular roles in de novo purine synthesis and purine nucleotide recycling. The biochemical phenotype of ADSL deficiency, accumulation of SAICAr and succinyladenosine (S-Ado in biofluids of affected individuals, serves as the traditional target for diagnosis with targeted quantitative urine purine analysis employed as the predominate method of detection. In this study, we report the diagnosis of ADSL deficiency using an alternative method, untargeted metabolomic profiling, an analytical scheme capable of generating semi-quantitative z-score values for over 1000 unique compounds in a single analysis of a specimen. Using this method to analyze plasma, we diagnosed ADSL deficiency in four patients and confirmed these findings with targeted quantitative biochemical analysis and molecular genetic testing. ADSL deficiency is part of a large a group of neurometabolic disorders, with a wide range of severity and sharing a broad differential diagnosis. This phenotypic similarity among these many inborn errors of metabolism (IEMs has classically stood as a hurdle in their initial diagnosis and subsequent treatment. The findings presented here demonstrate the clinical utility of metabolomic profiling in the diagnosis of ADSL deficiency and highlights the potential of this technology in the diagnostic evaluation of individuals with neurologic phenotypes.

  7. Hepatic fibrosis and carcinogenesis in α1-antitrypsin deficiency: a prototype for chronic tissue damage in gain-of-function disorders.

    Science.gov (United States)

    Perlmutter, David H; Silverman, Gary A

    2011-03-01

    In α1-antitrypsin (AT) deficiency, a point mutation renders a hepatic secretory glycoprotein prone to misfolding and polymerization. The mutant protein accumulates in the endoplasmic reticulum of liver cells and causes hepatic fibrosis and hepatocellular carcinoma by a gain-of-function mechanism. Genetic and/or environmental modifiers determine whether an affected homozygote is susceptible to hepatic fibrosis/carcinoma. Two types of proteostasis mechanisms for such modifiers have been postulated: variation in the function of intracellular degradative mechanisms and/or variation in the signal transduction pathways that are activated to protect the cell from protein mislocalization and/or aggregation. In recent studies we found that carbamazepine, a drug that has been used safely as an anticonvulsant and mood stabilizer, reduces the hepatic load of mutant AT and hepatic fibrosis in a mouse model by enhancing autophagic disposal of this mutant protein. These results provide evidence that pharmacological manipulation of endogenous proteostasis mechanisms is an appealing strategy for chemoprophylaxis in disorders involving gain-of-function mechanisms.

  8. Testosterone suppresses the expression of regulatory enzymes of fatty acid synthesis and protects against hepatic steatosis in cholesterol-fed androgen deficient mice.

    Science.gov (United States)

    Kelly, Daniel M; Nettleship, Joanne E; Akhtar, Samia; Muraleedharan, Vakkat; Sellers, Donna J; Brooke, Jonathan C; McLaren, David S; Channer, Kevin S; Jones, T Hugh

    2014-07-30

    Non-alcoholic fatty liver disease and its precursor hepatic steatosis is common in obesity and type-2 diabetes and is associated with cardiovascular disease (CVD). Men with type-2 diabetes and/or CVD have a high prevalence of testosterone deficiency. Testosterone replacement improves key cardiovascular risk factors. The effects of testosterone on hepatic steatosis are not fully understood. Testicular feminised (Tfm) mice, which have a non-functional androgen receptor (AR) and very low serum testosterone levels, were used to investigate testosterone effects on high-cholesterol diet-induced hepatic steatosis. Hepatic lipid deposition was increased in Tfm mice and orchidectomised wild-type littermates versus intact wild-type littermate controls with normal androgen physiology. Lipid deposition was reduced in Tfm mice receiving testosterone treatment compared to placebo. Oestrogen receptor blockade significantly, but only partially, reduced the beneficial effects of testosterone treatment on hepatic lipid accumulation. Expression of key regulatory enzymes of fatty acid synthesis, acetyl-CoA carboxylase alpha (ACACA) and fatty acid synthase (FASN) were elevated in placebo-treated Tfm mice versus placebo-treated littermates and Tfm mice receiving testosterone treatment. Tfm mice on normal diet had increased lipid accumulation compared to littermates but significantly less than cholesterol-fed Tfm mice and demonstrated increased gene expression of hormone sensitive lipase, stearyl-CoA desaturase-1 and peroxisome proliferator-activated receptor-gamma but FASN and ACACA were not altered. An action of testosterone on hepatic lipid deposition which is independent of the classic AR is implicated. Testosterone may act in part via an effect on the key regulatory lipogenic enzymes to protect against hepatic steatosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Analysis of Yellow Striped Mutants of Zea mays Reveals Novel Loci Contributing to Iron Deficiency Chlorosis

    Directory of Open Access Journals (Sweden)

    David Chan-Rodriguez

    2018-02-01

    Full Text Available The micronutrient iron (Fe is essential for photosynthesis, respiration, and many other processes, but it is only sparingly soluble in aqueous solution, making adequate acquisition by plants a serious challenge. Fe is a limiting factor for plant growth on approximately 30% of the world’s arable lands. Moreover, Fe deficiency in humans is a global health issue, affecting 1.62 billion people, or about 25% of the world’s population. It is imperative that we gain a better understanding of the mechanisms that plants use to regulate iron homeostasis, since these will be important targets for future biofortification and crop improvement strategies. Grasses and non-grasses have evolved independent mechanisms for primary iron uptake from the soil. The grasses, which include most of the world’s staple grains, have evolved a distinct ‘chelation’ mechanism to acquire iron from the soil. Strong iron chelators called phytosiderophores (PSs are synthesized by grasses and secreted into the rhizosphere where they bind and solubilize Fe(III. The Fe(III-PS complex is then taken up into root cells via transporters specific for the Fe(III-PS complex. In this study, 31 novel, uncharacterized striped maize mutants available through the Maize Genetics Cooperation Stock Center (MGCSC were analyzed to determine whether their mutant phenotypes are caused by decreased iron. Many of these proved to be either pale yellow or white striped mutants. Complementation tests were performed by crossing the MGCSC mutants to ys1 and ys3 reference mutants. This allowed assignment of 10 ys1 alleles and 4 ys3 alleles among the novel mutants. In addition, four ys∗ mutant lines were identified that are not allelic to either ys1 or ys3. Three of these were characterized as being non-allelic to each other and as having low iron in leaves. These represent new genes involved in iron acquisition by maize, and future cloning of these genes may reveal novel aspects of the grass iron

  10. Oral aversion to dietary sugar, ethanol and glycerol correlates with alterations in specific hepatic metabolites in a mouse model of human citrin deficiency.

    Science.gov (United States)

    Saheki, Takeyori; Inoue, Kanako; Ono, Hiromi; Fujimoto, Yuki; Furuie, Sumie; Yamamura, Ken-Ichi; Kuroda, Eishi; Ushikai, Miharu; Asakawa, Akihiro; Inui, Akio; Eto, Kazuhiro; Kadowaki, Takashi; Moriyama, Mitsuaki; Sinasac, David S; Yamamoto, Takashi; Furukawa, Tatsuhiko; Kobayashi, Keiko

    2017-04-01

    Mice carrying simultaneous homozygous mutations in the genes encoding citrin, the mitochondrial aspartate-glutamate carrier 2 (AGC2) protein, and mitochondrial glycerol-3-phosphate dehydrogenase (mGPD), are a phenotypically representative model of human citrin (a.k.a., AGC2) deficiency. In this study, we investigated the voluntary oral intake and preference for sucrose, glycerol or ethanol solutions by wild-type, citrin (Ctrn)-knockout (KO), mGPD-KO, and Ctrn/mGPD double-KO mice; all substances that are known or suspected precipitating factors in the pathogenesis of human citrin deficiency. The double-KO mice showed clear suppressed intake of sucrose, consuming less with progressively higher concentrations compared to the other mice. Similar observations were made when glycerol or ethanol were given. The preference of Ctrn-KO and mGPD-KO mice varied with the different treatments; essentially no differences were observed for sucrose, while an intermediate intake or similar to that of the double-KO mice was observed for glycerol and ethanol. We next examined the hepatic glycerol 3-phosphate, citrate, citrulline, lysine, glutamate and adenine nucleotide levels following forced enteral administration of these solutions. A strong correlation between the simultaneous increased hepatic glycerol 3-phosphate and decreased ATP or total adenine nucleotide content and observed aversion of the mice during evaluation of their voluntary preferences was found. Overall, our results suggest that the aversion observed in the double-KO mice to these solutions is initiated and/or mediated by hepatic metabolic perturbations, resulting in a behavioral response to increased hepatic cytosolic NADH and a decreased cellular adenine nucleotide pool. These findings may underlie the dietary predilections observed in human citrin deficient patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Urinary proteomic profiling reveals diclofenac-induced renal injury and hepatic regeneration in mice

    Energy Technology Data Exchange (ETDEWEB)

    Swelm, Rachel P.L. van [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Laarakkers, Coby M.M. [Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Pertijs, Jeanne C.L.M.; Verweij, Vivienne; Masereeuw, Rosalinde [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Russel, Frans G.M., E-mail: F.Russel@pharmtox.umcn.nl [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands)

    2013-06-01

    Diclofenac (DF) is a widely used non-steroidal anti-inflammatory drug for the treatment of rheumatic disorders, but is often associated with liver injury. We applied urinary proteomic profiling using MALDI-TOF MS to identify biomarkers for DF-induced hepatotoxicity in mice. Female CH3/HeOUJIco mice were treated with 75 mg/kg bw DF by oral gavage and 24 h urine was collected. Proteins identified in urine of DF-treated mice included epidermal growth factor, transthyretin, kallikrein, clusterin, fatty acid binding protein 1 and urokinase, which are related to liver regeneration but also to kidney injury. Both organs showed enhanced levels of oxidative stress (TBARS, p < 0.01). Kidney injury was confirmed by histology and increased Kim1 and Il-6 mRNA expression levels (p < 0.001 and p < 0.01). Liver histology and plasma ALT levels in DF-treated mice were not different from control, but mRNA expression of Stat3 (p < 0.001) and protein expression of PCNA (p < 0.05) were increased, indicating liver regeneration. In conclusion, urinary proteome analysis revealed that DF treatment in mice induced kidney and liver injury. Within 24 h, however, the liver was able to recover by activating tissue regeneration processes. Hence, the proteins found in urine of DF-treated mice represent kidney damage rather than hepatic injury. - Highlights: • The urinary proteome shows biological processes involved in adverse drug reactions. • Urine proteins of DF-treated mice relate to kidney injury rather than liver injury. • Liver regeneration, not liver injury, is apparent 24h after oral DF administration. • Pretreatment with LPS does not enhance DF-induced liver injury in mice.

  12. Human genetic deficiencies reveal the roles of complement in the inflammatory network: lessons from nature

    DEFF Research Database (Denmark)

    Lappegård, Knut Tore; Christiansen, Dorte; Pharo, Anne

    2009-01-01

    on CD14 and inversely regulated by complement, that is, complement deficiency and complement inhibition enhanced their release. Granulocyte responses were mainly complement-dependent, whereas monocyte responses were more dependent on CD14. Notably, all responses were abolished by combined neutralization...

  13. Proteomic and comparative genomic analysis reveals adaptability of Brassica napus to phosphorus-deficient stress.

    Science.gov (United States)

    Chen, Shuisen; Ding, Guangda; Wang, Zhenhua; Cai, Hongmei; Xu, Fangsen

    2015-03-18

    Given low solubility and immobility in many soils of the world, phosphorus (P) may be the most widely studied macronutrient for plants. In an attempt to gain an insight into the adaptability of Brassica napus to P deficiency, proteome alterations of roots and leaves in two B. napus contrasting genotypes, P-efficient 'Eyou Changjia' and P-inefficient 'B104-2', under long-term low P stress and short-term P-free starvation conditions were investigated, and proteomic combined with comparative genomic analyses were conducted to interpret the interrelation of differential abundance protein species (DAPs) responding to P deficiency with quantitative trait loci (QTLs) for P deficiency tolerance. P-efficient 'Eyou Changjia' had higher dry weight and P content, and showed high tolerance to low P stress compared with P-inefficient 'B104-2'. A total of 146 DAPs were successfully identified by MALDI TOF/TOF MS, which were categorized into several groups including defense and stress response, carbohydrate and energy metabolism, signaling and regulation, amino acid and fatty acid metabolism, protein process, biogenesis and cellular component, and function unknown. 94 of 146 DAPs were mapped to a linkage map constructed by a B. napus population derived from a cross between the two genotypes, and 72 DAPs were located in the confidence intervals of QTLs for P efficiency related traits. We conclude that the identification of these DAPs and the co-location of DAPs with QTLs in the B. napus linkage genetic map provide us novel information in understanding the adaptability of B. napus to P deficiency, and helpful to isolate P-efficient genes in B. napus. Low P seriously limits the production and quality of B. napus. Proteomics and genetic linkage map were widely used to study the adaptive strategies of B. napus response to P deficiency, proteomic combined with comparative genetic analysis to investigate the correlations between DAPs and QTLs are scarce. Thus, we herein investigated

  14. RNA-Seq profiling reveals novel hepatic gene expression pattern in aflatoxin B1 treated rats.

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    B Alex Merrick

    Full Text Available Deep sequencing was used to investigate the subchronic effects of 1 ppm aflatoxin B1 (AFB1, a potent hepatocarcinogen, on the male rat liver transcriptome prior to onset of histopathological lesions or tumors. We hypothesized RNA-Seq would reveal more differentially expressed genes (DEG than microarray analysis, including low copy and novel transcripts related to AFB1's carcinogenic activity compared to feed controls (CTRL. Paired-end reads were mapped to the rat genome (Rn4 with TopHat and further analyzed by DESeq and Cufflinks-Cuffdiff pipelines to identify differentially expressed transcripts, new exons and unannotated transcripts. PCA and cluster analysis of DEGs showed clear separation between AFB1 and CTRL treatments and concordance among group replicates. qPCR of eight high and medium DEGs and three low DEGs showed good comparability among RNA-Seq and microarray transcripts. DESeq analysis identified 1,026 differentially expressed transcripts at greater than two-fold change (p<0.005 compared to 626 transcripts by microarray due to base pair resolution of transcripts by RNA-Seq, probe placement within transcripts or an absence of probes to detect novel transcripts, splice variants and exons. Pathway analysis among DEGs revealed signaling of Ahr, Nrf2, GSH, xenobiotic, cell cycle, extracellular matrix, and cell differentiation networks consistent with pathways leading to AFB1 carcinogenesis, including almost 200 upregulated transcripts controlled by E2f1-related pathways related to kinetochore structure, mitotic spindle assembly and tissue remodeling. We report 49 novel, differentially-expressed transcripts including confirmation by PCR-cloning of two unique, unannotated, hepatic AFB1-responsive transcripts (HAfT's on chromosomes 1.q55 and 15.q11, overexpressed by 10 to 25-fold. Several potentially novel exons were found and exon refinements were made including AFB1 exon-specific induction of homologous family members, Ugt1a6 and Ugt1a7c

  15. RNA-Seq profiling reveals novel hepatic gene expression pattern in aflatoxin B1 treated rats.

    Science.gov (United States)

    Merrick, B Alex; Phadke, Dhiral P; Auerbach, Scott S; Mav, Deepak; Stiegelmeyer, Suzy M; Shah, Ruchir R; Tice, Raymond R

    2013-01-01

    Deep sequencing was used to investigate the subchronic effects of 1 ppm aflatoxin B1 (AFB1), a potent hepatocarcinogen, on the male rat liver transcriptome prior to onset of histopathological lesions or tumors. We hypothesized RNA-Seq would reveal more differentially expressed genes (DEG) than microarray analysis, including low copy and novel transcripts related to AFB1's carcinogenic activity compared to feed controls (CTRL). Paired-end reads were mapped to the rat genome (Rn4) with TopHat and further analyzed by DESeq and Cufflinks-Cuffdiff pipelines to identify differentially expressed transcripts, new exons and unannotated transcripts. PCA and cluster analysis of DEGs showed clear separation between AFB1 and CTRL treatments and concordance among group replicates. qPCR of eight high and medium DEGs and three low DEGs showed good comparability among RNA-Seq and microarray transcripts. DESeq analysis identified 1,026 differentially expressed transcripts at greater than two-fold change (p<0.005) compared to 626 transcripts by microarray due to base pair resolution of transcripts by RNA-Seq, probe placement within transcripts or an absence of probes to detect novel transcripts, splice variants and exons. Pathway analysis among DEGs revealed signaling of Ahr, Nrf2, GSH, xenobiotic, cell cycle, extracellular matrix, and cell differentiation networks consistent with pathways leading to AFB1 carcinogenesis, including almost 200 upregulated transcripts controlled by E2f1-related pathways related to kinetochore structure, mitotic spindle assembly and tissue remodeling. We report 49 novel, differentially-expressed transcripts including confirmation by PCR-cloning of two unique, unannotated, hepatic AFB1-responsive transcripts (HAfT's) on chromosomes 1.q55 and 15.q11, overexpressed by 10 to 25-fold. Several potentially novel exons were found and exon refinements were made including AFB1 exon-specific induction of homologous family members, Ugt1a6 and Ugt1a7c. We find the

  16. NADH:ubiquinone reductase and succinate dehydrogenase activity in the liver of rats with acetaminophen-induced toxic hepatitis on the background of alimentary protein deficiency

    Directory of Open Access Journals (Sweden)

    G. P. Kopylchuk

    2015-02-01

    Full Text Available The ratio between the redox forms of the nicotinamide coenzymes and key enzymatic activity of the I and II respiratory chain complexes in the liver cells mitochondria of rats with acetaminophen-induced hepatitis under the conditions of alimentary deprivation of protein was studied. It was estimated, that under the conditions of acute acetaminophen-induced hepatitis of rats kept on a low-protein diet during 4 weeks a significant decrease of the NADH:ubiquinone reductase and succinate dehydrogenase activity with simultaneous increase of the ratio between redox forms of the nicotinamide coenzymes (NAD+/NADН is observed compared to the same indices in the liver cells of animals with experimental hepatitis kept on the ration balanced by all nutrients. Results of research may become basic ones for the biochemical rationale for the approaches directed to the correction and elimination of the consequences­ of energy exchange in the toxic hepatitis, induced on the background of protein deficiency.

  17. Emergence of hepatitis C virus genotype 4: phylogenetic analysis reveals three distinct epidemiological profiles

    NARCIS (Netherlands)

    de Bruijne, Joep; Schinkel, Janke; Prins, Maria; Koekkoek, Sylvie M.; Aronson, Sem J.; van Ballegooijen, Marijn W.; Reesink, Hendrik W.; Molenkamp, Richard; van de Laar, Thijs J. W.

    2009-01-01

    Hepatitis C virus (HCV) genotype 4 (HCV-4) infection is considered to be difficult to treat and has become increasingly prevalent in European countries, including The Netherlands. Using a molecular epidemiological approach, the present study investigates the genetic diversity and evolutionary origin

  18. PGC-1alpha Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis

    Directory of Open Access Journals (Sweden)

    Leone Teresa C

    2005-01-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha-/- mice. With age, the PGC-1alpha-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  19. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis.

    Directory of Open Access Journals (Sweden)

    Teresa C Leone

    2005-04-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha(-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha(-/- mice. With age, the PGC-1alpha(-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha(-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  20. Internal jugular vein thrombosis associated with venous hypoplasia and protein S deficiency revealed by ultrasonography.

    Science.gov (United States)

    Lim, Byung Gun; Kim, Young Min; Kim, Heezoo; Lim, Sang Ho; Lee, Mi Kyoung

    2011-12-01

    A 41-year-old woman, who had no thrombotic risk factors and past history except congenital scoliosis, underwent central venous catheterization (CVC) before correction of the scoliosis. When internal jugular vein (IJV) catheterization using the anatomical landmark technique failed, CVC under ultrasound guidance was tried. As a consequence, thrombosis and hypoplasia of the right IJV were incidentally detected by ultrasonography. Central venous catheters were then successfully placed in other veins under ultrasound guidance. Also, after examinations to rule out the possibility of pulmonary embolism and to clarify the causes of the IJV thrombosis, the patient was found to have protein S deficiency. CVC under ultrasound guidance should be recommended to prevent the failure of cannulation and complications such as thromboembolism in patients who could possibly have anomalies of vessels as a result of anatomical deformities caused by severe scoliosis, even if patients do not have thrombotic risk factors such as a history of central catheter insertion or intravenous drug abuse, cancer, advanced age, cerebral infarction, and left ventricular dysfunction. Also, if venous thrombosis is found in patients without predisposing risk factors, one should ascertain the cause of the hypercoagulable state, for example protein S deficiency, and perform appropriate treatment and prevention of venous thromboembolism.

  1. Hepatitis B and C Sero-prevalence in Patients with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome at a Tertiary Care Hospital in Izmir

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    Sabri ATALAY

    2018-04-01

    Full Text Available Objectives: Infections caused by human immunodeficiency virus (HIV, hepatitis B virus (HBV and hepatitis C virus (HCV represent a significant health problem. Co-infection with these viral agents is not uncommon as a result of the similar transmission routes. Our study was planned to investigate the prevalence of HBV and HCV infections in HIV/Acquired Immune Deficiency syndrome (AIDS patients followed up at our institution. Materials and Methods: In this study conducted in the Department of Infectious Diseases and Clinical Microbiology at Izmir Tepecik Training and Research Hospital, medical records of patients followed at the HIV/AIDS outpatient clinic between August 2002 and December 2014 were evaluated. Demographic data, main route of HIV transmission, hepatitis B surface antigen (HBsAg, anti-hepatitis B core (HBc immunoglobulin G (IgG, anti-HBs and anti-HCV results were evaluated. Results: A total of 157 treatment-naïve patients who were followed up at our HIV/AIDS outpatient clinic were included in this study. Four patients (2.6%, had HBsAg positivity. Anti-HBc IgG and anti-HBs positivity were detected in 34% and 28.4% of the patients, respectively. No patients had anti-HCV positivity. Conclusion: The prevalence of HBsAg in HIV-positive individuals was found to be similar to that in other population-based studies in our country. Absence of anti-HCV positivity suggests that hepatitis C infection is not a major health problem in this population.

  2. Phonological abilities in literacy-impaired children: Brain potentials reveal deficient phoneme discrimination, but intact prosodic processing

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    Claudia Männel

    2017-02-01

    Full Text Available Intact phonological processing is crucial for successful literacy acquisition. While individuals with difficulties in reading and spelling (i.e., developmental dyslexia are known to experience deficient phoneme discrimination (i.e., segmental phonology, findings concerning their prosodic processing (i.e., suprasegmental phonology are controversial. Because there are no behavior-independent studies on the underlying neural correlates of prosodic processing in dyslexia, these controversial findings might be explained by different task demands. To provide an objective behavior-independent picture of segmental and suprasegmental phonological processing in impaired literacy acquisition, we investigated event-related brain potentials during passive listening in typically and poor-spelling German school children. For segmental phonology, we analyzed the Mismatch Negativity (MMN during vowel length discrimination, capturing automatic auditory deviancy detection in repetitive contexts. For suprasegmental phonology, we analyzed the Closure Positive Shift (CPS that automatically occurs in response to prosodic boundaries. Our results revealed spelling group differences for the MMN, but not for the CPS, indicating deficient segmental, but intact suprasegmental phonological processing in poor spellers. The present findings point towards a differential role of segmental and suprasegmental phonology in literacy disorders and call for interventions that invigorate impaired literacy by utilizing intact prosody in addition to training deficient phonemic awareness.

  3. Structure of Hepatitis E Virion-Sized Particle Reveals an RNA-Dependent Viral Assembly Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xing, L.; Wall, J.; Li, T.-C.; Mayazaki, N.; Simon, M. N.; Moore, M.; Wang, C.-Y.; Takeda, N.; Wakita, T.; Miyamura, T.; Cheng, R. H.

    2010-10-22

    Hepatitis E virus (HEV) induces acute hepatitis in humans with a high fatality rate in pregnant women. There is a need for anti-HEV research to understand the assembly process of HEV native capsid. Here, we produced a large virion-sized and a small T=1 capsid by expressing the HEV capsid protein in insect cells with and without the N-terminal 111 residues, respectively, for comparative structural analysis. The virion-sized capsid demonstrates a T=3 icosahedral lattice and contains RNA fragment in contrast to the RNA-free T=1 capsid. However, both capsids shared common decameric organization. The in vitro assembly further demonstrated that HEV capsid protein had the intrinsic ability to form decameric intermediate. Our data suggest that RNA binding is the extrinsic factor essential for the assembly of HEV native capsids.

  4. Genomic Analysis of Hepatitis B Virus Reveals Antigen State and Genotype as Sources of Evolutionary Rate Variation

    Science.gov (United States)

    Harrison, Abby; Lemey, Philippe; Hurles, Matthew; Moyes, Chris; Horn, Susanne; Pryor, Jan; Malani, Joji; Supuri, Mathias; Masta, Andrew; Teriboriki, Burentau; Toatu, Tebuka; Penny, David; Rambaut, Andrew; Shapiro, Beth

    2011-01-01

    Hepatitis B virus (HBV) genomes are small, semi-double-stranded DNA circular genomes that contain alternating overlapping reading frames and replicate through an RNA intermediary phase. This complex biology has presented a challenge to estimating an evolutionary rate for HBV, leading to difficulties resolving the evolutionary and epidemiological history of the virus. Here, we re-examine rates of HBV evolution using a novel data set of 112 within-host, transmission history (pedigree) and among-host genomes isolated over 20 years from the indigenous peoples of the South Pacific, combined with 313 previously published HBV genomes. We employ Bayesian phylogenetic approaches to examine several potential causes and consequences of evolutionary rate variation in HBV. Our results reveal rate variation both between genotypes and across the genome, as well as strikingly slower rates when genomes are sampled in the Hepatitis B e antigen positive state, compared to the e antigen negative state. This Hepatitis B e antigen rate variation was found to be largely attributable to changes during the course of infection in the preCore and Core genes and their regulatory elements. PMID:21765983

  5. Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients

    Directory of Open Access Journals (Sweden)

    Cedric Simillion

    2017-10-01

    Full Text Available About one in 15 of the world’s population is chronically infected with either hepatitis virus B (HBV or C (HCV, with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states.

  6. Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice

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    Ran Huimin

    2008-08-01

    Full Text Available Abstract Background Prosaposin encodes, in tandem, four small acidic activator proteins (saposins with specificities for glycosphingolipid (GSL hydrolases in lysosomes. Extensive GSL storage occurs in various central nervous system regions in mammalian prosaposin deficiencies. Results Our hypomorphic prosaposin deficient mouse, PS-NA, exhibited 45% WT levels of brain saposins and showed neuropathology that included neuronal GSL storage and Purkinje cell loss. Impairment of neuronal function was observed as early as 6 wks as demonstrated by the narrow bridges tests. Temporal transcriptome microarray analyses of brain tissues were conducted with mRNA from three prosaposin deficient mouse models: PS-NA, prosaposin null (PS-/- and a V394L/V394L glucocerebrosidase mutation combined with PS-NA (4L/PS-NA. Gene expression alterations in cerebrum and cerebellum were detectable at birth preceding the neuronal deficits. Differentially expressed genes encompassed a broad spectrum of cellular functions. The number of down-regulated genes was constant, but up-regulated gene numbers increased with age. CCAAT/enhancer-binding protein delta (CEBPD was the only up-regulated transcription factor in these two brain regions of all three models. Network analyses revealed that CEBPD has functional relationships with genes in transcription, pro-inflammation, cell death, binding, myelin and transport. Conclusion These results show that: 1 Regionally specific gene expression abnormalities precede the brain histological and neuronal function changes, 2 Temporal gene expression profiles provide insights into the molecular mechanism during the GSL storage disease course, and 3 CEBPD is a candidate regulator of brain disease in prosaposin deficiency to participate in modulating disease acceleration or progression.

  7. Concomitant homozygosity for the prothrombin gene variant with mild deficiency of antithrombin III in a patient with multiple hepatic infarctions: a case report

    Directory of Open Access Journals (Sweden)

    Macheta M

    2010-04-01

    Full Text Available Abstract Introduction Hereditary causes of visceral thrombosis or thrombosis should be sought among young patients. We present a case of a young man presenting with multiple hepatic infarctions resulting in portal hypertension due to homozygosity of the prothrombin gene mutation not previously described in literature. Case presentation A 42-year-old Caucasian man with a previous history of idiopathic deep vein thrombosis 11 years earlier presented with vague abdominal pains and mildly abnormal liver function tests. An ultrasound and computed tomography scan showed evidence of hepatic infarction and portal hypertension (splenic varices. A thrombophilia screen confirmed a homozygous mutation for the prothrombin gene mutation, with mildly reduced levels of anti-thrombin III (AT III. Subsequent testing of his father and brother revealed heterozygosity for the same gene mutation. Conclusion Hepatic infarction is unusual due to the rich dual arterial and venous blood supply to the liver. In the absence of an arterial or haemodynamic insult causing hepatic infarction, a thrombophilia should be considered. To our knowledge, this is the first reported case of a hepatic infarction due to homozygosity of the prothrombin gene mutation. It is unclear whether homozygotes have a higher risk of thrombosis than heterozygotes. In someone presenting with a first thrombosis with this mutation, the case for life-long anticoagulation is unclear, but it may be necessary to prevent a second and more severe second thrombotic event, as occurred in this case.

  8. Additive effects of clofibric acid and pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) deficiency on hepatic steatosis in mice fed a high-saturated fat diet

    Science.gov (United States)

    Hwang, Byounghoon; Wu, Pengfei; Harris, Robert A.

    2012-01-01

    SUMMARY Although improving glucose metabolism by inhibition of pyruvate dehydrogenase kinase 4 (PDK4) might prove beneficial in the treatment of type 2 diabetes or diet-induced obesity, it might induce detrimental effects by inhibiting fatty acid oxidation. PPARα agonists are often used to treat dyslipidemia in patients, especially in type 2 diabetes. Combinational treatment with a PDK4 inhibitor and PPARα agonists may prove beneficial. However, PPARα agonists may be less effective in the presence of a PDK4 inhibitor because PPARα agonists induce PDK4 expression. In the present study, the effects of clofibric acid, a PPARα agonist, on blood and liver lipids were determined in wild type and PDK4 knockout mice fed a high fat diet. As expected, treatment of wild type mice with clofibric acid resulted in less body weight gain, smaller epididymal fat pads, greater insulin sensitivity, and lower levels of serum and liver triacylglycerol. Surprisingly, rather than decreasing the effectiveness of clofibric acid, PDK4 deficiency enhanced the beneficial effects of clofibric acid on hepatic steatosis, lowered blood glucose levels, and did not prevent the positive effects of clofibric acid on serum triacylglycerols and free fatty acids. The metabolic effects of clofibric acid are therefore independent of the induction of PDK4 expression. The additive beneficial effects on hepatic steatosis may be due to induction of increased capacity for fatty acid oxidation and partial uncoupling of oxidative phosphorylation by clofibric acid and a reduction in the capacity for fatty acid synthesis by PDK4 deficiency. PMID:22429297

  9. Niemann-Pick C1-deficient mice lacking sterol O-acyltransferase 2 have less hepatic cholesterol entrapment and improved liver function.

    Science.gov (United States)

    Lopez, Adam M; Jones, Ryan Dale; Repa, Joyce J; Turley, Stephen D

    2018-06-07

    Cholesteryl esters are generated at multiple sites in the body by sterol O-acyltransferase 1 (SOAT1) or sterol O-acyltransferase 2 (SOAT2) in various cell types, and lecithin cholesterol acyltransferase (LCAT) in plasma. Esterified cholesterol (EC) and triacylglycerol (TAG) contained in lipoproteins cleared from the circulation via receptor-mediated or bulk-phase endocytosis are hydrolyzed by lysosomal acid lipase (LAL) within the late endosomal/lysosomal (E/L) compartment. Then, through the successive actions of Niemann-Pick C2 (NPC2) and Niemann-Pick C1 (NPC1), unesterified cholesterol (UC) is exported from the E/L compartment to the cytosol. Mutations in either NPC1 or NPC2 lead to continuing entrapment of UC in all organs, resulting in multisystem disease which includes hepatic dysfunction and in some cases liver failure. These studies investigated primarily whether elimination of SOAT2 in NPC1-deficient mice impacted hepatic UC sequestration, inflammation, and transaminase activities. Measurements were made in 7 wk-old mice fed a low-cholesterol chow diet or one enriched with cholesterol starting 2 wk before study. In the chow-fed mice, NPC1:SOAT2 double knockouts, compared to their littermates lacking only NPC1, had 20% less liver mass, 28% lower hepatic UC concentrations, and plasma ALT and AST activities that were decreased by 48% and 36%, respectively. mRNA expression levels for several markers of inflammation were all significantly lower in the NPC1 mutants lacking SOAT2. The existence of a new class of potent and selective SOAT2 inhibitors provides an opportunity for exploring if suppression of this enzyme could potentially become an adjunctive therapy for liver disease in NPC1 deficiency.

  10. Brain transcriptional responses to high-fat diet in Acads-deficient mice reveal energy sensing pathways.

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    Claudia Kruger

    Full Text Available How signals from fatty acid metabolism are translated into changes in food intake remains unclear. Previously we reported that mice with a genetic inactivation of Acads (acyl-coenzyme A dehydrogenase, short-chain, the enzyme responsible for mitochondrial beta-oxidation of C4-C6 short-chain fatty acids (SCFAs, shift consumption away from fat and toward carbohydrate when offered a choice between diets. In the current study, we sought to indentify candidate genes and pathways underlying the effects of SCFA oxidation deficiency on food intake in Acads-/- mice.We performed a transcriptional analysis of gene expression in brain tissue of Acads-/- and Acads+/+ mice fed either a high-fat (HF or low-fat (LF diet for 2 d. Ingenuity Pathway Analysis revealed three top-scoring pathways significantly modified by genotype or diet: oxidative phosphorylation, mitochondrial dysfunction, and CREB signaling in neurons. A comparison of statistically significant responses in HF Acads-/- vs. HF Acads+/+ (3917 and Acads+/+ HF vs. LF Acads+/+ (3879 revealed 2551 genes or approximately 65% in common between the two experimental comparisons. All but one of these genes were expressed in opposite direction with similar magnitude, demonstrating that HF-fed Acads-deficient mice display transcriptional responses that strongly resemble those of Acads+/+ mice fed LF diet. Intriguingly, genes involved in both AMP-kinase regulation and the neural control of food intake followed this pattern. Quantitative RT-PCR in hypothalamus confirmed the dysregulation of genes in these pathways. Western blotting showed an increase in hypothalamic AMP-kinase in Acads-/- mice and HF diet increased, a key protein in an energy-sensing cascade that responds to depletion of ATP.Our results suggest that the decreased beta-oxidation of short-chain fatty acids in Acads-deficient mice fed HF diet produces a state of energy deficiency in the brain and that AMP-kinase may be the cellular energy

  11. Seroprevalence of hepatitis and human immuno-deficiency virus in multitransfused patients from a pediatric hematology clinic

    Directory of Open Access Journals (Sweden)

    Suar Çakı Kılıç

    2008-12-01

    Full Text Available OBJECTIVE: Transfusion transmitted hepatitis has been a severe problem in Turkey in pediatric cancer patients and in chronic congenital anemia. The aim of the present study was to investigate the prevalence of hepatitis B, hepatitis C and human immunodeficiency virus infections in these patients in a University Hospital. METHODS: Multi-transfused 66 children (59 acute leukemia, 6 thalassemia major, 1 severe hereditary spherocytosis diagnosed and followed-up between May, 2000 and December, 2006 were evaluated. Screening of all the patients for HbsAg, anti-HBs, anti-HBc, anti-HCV and anti-HIV was performed at presentation and during the last follow-up. Serologic studies of leukemic patients were also repeated at the end of the chemotherapy. Hepatitis B vaccination was administered to unvaccinated patients with anemia. All blood products were provided by Blood Bank of the Center. RESULTS: No patient was found HBsAg, anti-HCV or anti-HIV positive at diagnosis and at the end of the therapy. There was history of hepatitis B vaccination in only 42% of the patients at diagnosis due to administration of this vaccine to newborns since 1998. At the beginning of the study, 45 % (n=27 of the leukemic patients were immune for hepatitis B, but after completion of the intensive chemotherapy seropositivity persisted in only 28.8 % (n=17. CONCLUSION: Transmission of these viruses is no longer a real problem even in multitransfused immunosuppressed children in Pediatric Hematology Units as a result of the improvements in screening of voluntary blood donors, administration of disposable material in clinics and vaccination by hepatitis B.

  12. Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.

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    Matthew S Barnabei

    Full Text Available Duchenne muscular dystrophy (DMD is a progressive and fatal disease of muscle wasting caused by loss of the cytoskeletal protein dystrophin. In the heart, DMD results in progressive cardiomyopathy and dilation of the left ventricle through mechanisms that are not fully understood. Previous reports have shown that loss of dystrophin causes sarcolemmal instability and reduced mechanical compliance of isolated cardiac myocytes. To expand upon these findings, here we have subjected the left ventricles of dystrophin-deficient mdx hearts to mechanical stretch. Unexpectedly, isolated mdx hearts showed increased left ventricular (LV compliance compared to controls during stretch as LV volume was increased above normal end diastolic volume. During LV chamber distention, sarcomere lengths increased similarly in mdx and WT hearts despite greater excursions in volume of mdx hearts. This suggests that the mechanical properties of the intact heart cannot be modeled as a simple extrapolation of findings in single cardiac myocytes. To explain these findings, a model is proposed in which disruption of the dystrophin-glycoprotein complex perturbs cell-extracellular matrix contacts and promotes the apparent slippage of myocytes past each other during LV distension. In comparison, similar increases in LV compliance were obtained in isolated hearts from β-sarcoglycan-null and laminin-α(2 mutant mice, but not in dysferlin-null mice, suggesting that increased whole-organ compliance in mdx mice is a specific effect of disrupted cell-extracellular matrix contacts and not a general consequence of cardiomyopathy via membrane defect processes. Collectively, these findings suggest a novel and cell-death independent mechanism for the progressive pathological LV dilation that occurs in DMD.

  13. Assessment of triple-phase CT findings for the differentiation of fat-deficient hepatic angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver

    International Nuclear Information System (INIS)

    Jeon, Tae Yeon; Kim, Seong Hyun; Lim, Hyo K.; Lee, Won Jae

    2010-01-01

    Background: To evaluate the triple-phase CT findings for the differentiation of fat-deficient angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver. Methods: We retrospectively reviewed contrast-enhanced triple-phase CT images of 10 patients with fat-deficient hepatic angiomyolipoma and 28 patients with 29 hepatocellular carcinomas in non-cirrhotic liver proved on histologic examination. The CT findings for the two types of tumors were compared using Fisher's exact test. Results: Early draining vein depicted on arterial or portal phases was seen in eight (80%) angiomyolipomas and two hepatocellular carcinomas (7%) (p < 0.001), in which the early draining vein was connected with tumoral vessels. The tumoral vessels in the angiomyolipoma were more prominent and ectatic, were distributed both centrally and peripherally, and were seen in smaller tumors than in the hepatocellular carcinoma. Tumor capsule enhancement was absent in all angiomyolipomas as compared with two (7%) hepatocellular carcinomas with no tumor capsule (p < 0.001). The other CT findings were not significantly different for the two different types of tumors. Conclusions: The presence of early draining vein connecting with prominent tumoral vessels and absent tumor capsule were useful CT findings for the differentiation of fat-deficient angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver.

  14. Expression analysis revealing destabilizing mutations in phosphomannomutase 2 deficiency (PMM2-CDG): expression analysis of PMM2-CDG mutations.

    Science.gov (United States)

    Vega, Ana Isabel; Pérez-Cerdá, Celia; Abia, David; Gámez, Alejandra; Briones, Paz; Artuch, Rafael; Desviat, Lourdes R; Ugarte, Magdalena; Pérez, Belén

    2011-08-01

    Deficiency of phosphomannomutase (PMM2, MIM#601785) is the most common congenital disorder of glycosylation. Herein we report the genetic analysis of 22 Spanish PMM2 deficient patients and the functional analysis of 14 nucleotide changes in a prokaryotic expression system in order to elucidate their molecular pathogenesis. PMM2 activity assay revealed the presence of six protein changes with no enzymatic activities (p.R123Q, p.R141H, p.F157S, p.P184T, p.F207S and p.D209G) and seven mild protein changes with residual activities ranging from 16 to 54% (p.L32R, p.V44A p.D65Y, p.P113L p.T118S, p.T237M and p.C241S) and also one variant change with normal activity (p.E197A). The results obtained from Western blot analysis, degradation time courses of 11 protein changes and structural analysis of the PMM2 protein, suggest that the loss-of-function of most mutant proteins is based on their increased susceptibility to degradation or aggregation compared to the wild type protein, considering PMM2 deficiency as a conformational disease. We have identified exclusively catalytic protein change (p.D209G), catalytic protein changes affecting protein stability (p.R123Q and p.R141H), two protein changes disrupting the dimer interface (p.P113L and p.T118S) and several misfolding changes (p.L32R, p.V44A, p.D65Y, p.F157S, p.P184T, p.F207S, p.T237M and p.C241S). Our current work opens a promising therapeutic option using pharmacological chaperones to revert the effect of the characterized misfolding mutations identified in a wide range of PMM2 deficient patients.

  15. Deficiency in the mitochondrial apoptotic pathway reveals the toxic potential of autophagy under ER stress conditions.

    Science.gov (United States)

    Deegan, Shane; Saveljeva, Svetlana; Logue, Susan E; Pakos-Zebrucka, Karolina; Gupta, Sanjeev; Vandenabeele, Peter; Bertrand, Mathieu J M; Samali, Afshin

    2014-01-01

    Endoplasmic reticulum (ER) stress-induced cell death is normally associated with activation of the mitochondrial apoptotic pathway, which is characterized by CYCS (cytochrome c, somatic) release, apoptosome formation, and caspase activation, resulting in cell death. In this study, we demonstrate that under conditions of ER stress cells devoid of CASP9/caspase-9 or BAX and BAK1, and therefore defective in the mitochondrial apoptotic pathway, still undergo a delayed form of cell death associated with the activation of caspases, therefore revealing the existence of an alternative stress-induced caspase activation pathway. We identified CASP8/caspase-8 as the apical protease in this caspase cascade, and found that knockdown of either of the key autophagic genes, ATG5 or ATG7, impacted on CASP8 activation and cell death induction, highlighting the crucial role of autophagy in the activation of this novel ER stress-induced death pathway. In line with this, we identified a protein complex composed of ATG5, FADD, and pro-CASP8 whose assembly coincides with caspase activation and cell death induction. Together, our results reveal the toxic potential of autophagy in cells undergoing ER stress that are defective in the mitochondrial apoptotic pathway, and suggest a model in which the autophagosome functions as a platform facilitating pro-CASP8 activation. Chemoresistance, a common problem in the treatment of cancer, is frequently caused by the downregulation of key mitochondrial death effector proteins. Alternate stress-induced apoptotic pathways, such as the one described here, may become of particular relevance for tackling the problem of chemoresistance in cancer cells.

  16. Deficiency of NOX1 or NOX4 Prevents Liver Inflammation and Fibrosis in Mice through Inhibition of Hepatic Stellate Cell Activation.

    Directory of Open Access Journals (Sweden)

    Tian Lan

    Full Text Available Reactive oxygen species (ROS produced by nicotinamide adenine dinucleotide phosphate oxidase (NOX play a key role in liver injury and fibrosis. Previous studies demonstrated that GKT137831, a dual NOX1/4 inhibitor, attenuated liver fibrosis in mice as well as pro-fibrotic genes in hepatic stellate cells (HSCs as well as hepatocyte apoptosis. The effect of NOX1 and NOX4 deficiency in liver fibrosis is unclear, and has never been directly compared. HSCs are the primary myofibroblasts in the pathogenesis of liver fibrosis. Therefore, we aimed to determine the role of NOX1 and NOX4 in liver fibrosis, and investigated whether NOX1 and NOX4 signaling mediates liver fibrosis by regulating HSC activation. Mice were treated with carbon tetrachloride (CCl4 to induce liver fibrosis. Deficiency of either NOX1 or NOX4 attenuates liver injury, inflammation, and fibrosis after CCl4 compared to wild-type mice. NOX1 or NOX4 deficiency reduced lipid peroxidation and ROS production in mice with liver fibrosis. NOX1 and NOX4 deficiency are approximately equally effective in preventing liver injury in the mice. The NOX1/4 dual inhibitor GKT137831 suppressed ROS production as well as inflammatory and proliferative genes induced by lipopolysaccharide (LPS, platelet-derived growth factor (PDGF, or sonic hedgehog (Shh in primary mouse HSCs. Furthermore, the mRNAs of proliferative and pro-fibrotic genes were downregulated in NOX1 and NOX4 knock-out activated HSCs (cultured on plastic for 5 days. Finally, NOX1 and NOX4 protein levels were increased in human livers with cirrhosis compared with normal controls. Thus, NOX1 and NOX4 signaling mediates the pathogenesis of liver fibrosis, including the direct activation of HSC.

  17. A Shotgun Proteomic Approach Reveals That Fe Deficiency Causes Marked Changes in the Protein Profiles of Plasma Membrane and Detergent-Resistant Microdomain Preparations from Beta vulgaris Roots.

    Science.gov (United States)

    Gutierrez-Carbonell, Elain; Takahashi, Daisuke; Lüthje, Sabine; González-Reyes, José Antonio; Mongrand, Sébastien; Contreras-Moreira, Bruno; Abadía, Anunciación; Uemura, Matsuo; Abadía, Javier; López-Millán, Ana Flor

    2016-08-05

    In the present study we have used label-free shotgun proteomic analysis to examine the effects of Fe deficiency on the protein profiles of highly pure sugar beet root plasma membrane (PM) preparations and detergent-resistant membranes (DRMs), the latter as an approach to study microdomains. Altogether, 545 proteins were detected, with 52 and 68 of them changing significantly with Fe deficiency in PM and DRM, respectively. Functional categorization of these proteins showed that signaling and general and vesicle-related transport accounted for approximately 50% of the differences in both PM and DRM, indicating that from a qualitative point of view changes induced by Fe deficiency are similar in both preparations. Results indicate that Fe deficiency has an impact in phosphorylation processes at the PM level and highlight the involvement of signaling proteins, especially those from the 14-3-3 family. Lipid profiling revealed Fe-deficiency-induced decreases in phosphatidic acid derivatives, which may impair vesicle formation, in agreement with the decreases measured in proteins related to intracellular trafficking and secretion. The modifications induced by Fe deficiency in the relative enrichment of proteins in DRMs revealed the existence of a group of cytoplasmic proteins that appears to be more attached to the PM in conditions of Fe deficiency.

  18. Fatal hepatic short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency: clinical, biochemical, and pathological studies on three subjects with this recently identified disorder of mitochondrial beta-oxidation

    NARCIS (Netherlands)

    Bennett, M. J.; Spotswood, S. D.; Ross, K. F.; Comfort, S.; Koonce, R.; Boriack, R. L.; IJlst, L.; Wanders, R. J.

    1999-01-01

    This report describes the clinical, biochemical, and pathological findings in three infants with hepatic short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD) deficiency, a recently recognized disorder of the mitochondrial oxidation of straight-chain fatty acids. Candidate subjects were

  19. Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats.

    Science.gov (United States)

    Kobayashi, Misato; Hoshinaga, Yukiko; Miura, Natsuko; Tokuda, Yuki; Shigeoka, Shigeru; Murai, Atsushi; Horio, Fumihiko

    2014-01-01

    The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.

  20. Enhancing hepatic fibrosis in spontaneously hypertensive rats fed a choline-deficient diet: a follow-up report on long-term effects of oxidative stress in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Yamamoto, Hiroya; Kanno, Keishi; Ikuta, Takuya; Arihiro, Koji; Sugiyama, Akiko; Kishikawa, Nobusuke; Tazuma, Susumu

    2016-05-01

    We previously reported a model of non-alcoholic fatty liver disease (NAFLD) using spontaneously hypertensive rats (SHRs), fed a choline-deficient (CD) diet for 5 weeks, that hepatic steatosis but not fibrosis is developed through oxidative stress. To determine the relationship between hypertension and hepatic fibrosis in NAFLD, we examined whether long-term CD diet leads to hepatic fibrosis through oxidative stress. Eight-week-old male SHR and normotensive Wistar Kyoto rats (WKYs) were fed a CD diet for 5 or 20 weeks, then liver histology and hepatic expression of genes related to lipid metabolism, fibrosis, and oxidative stress were assessed. Oxidative stress was assessed by hepatic thiobarbituric acid reactive substance (TBARS) levels. After 5 weeks on CD diet, prominent hepatic steatosis and decrease in expression of genes for lipid metabolism were observed in SHRs as compared with WKYs. SHRs on a CD diet demonstrated a downregulated expression of genes for antioxidants, along with significant increases in hepatic TBARS. After 20 weeks on CD diet, SHRs demonstrated severe liver fibrosis and upregulated expressions of genes for fibrosis when compared with WKY. Hypertension precipitated hepatic steatosis, and further, acts as an enhancer in NAFLD progression to liver fibrosis through oxidative stress. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  1. IL-15 deficient tax mice reveal a role for IL-1α in tumor immunity.

    Directory of Open Access Journals (Sweden)

    Daniel A Rauch

    Full Text Available IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia/lymphoma (ATL and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15(-/- TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma.

  2. Additive effects of clofibric acid and pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) deficiency on hepatic steatosis in mice fed a high saturated fat diet.

    Science.gov (United States)

    Hwang, Byounghoon; Wu, Pengfei; Harris, Robert A

    2012-05-01

    Although improving glucose metabolism by inhibition of pyruvate dehydrogenase kinase 4 (PDK4) may prove beneficial in the treatment of type 2 diabetes or diet-induced obesity, it may have detrimental effects by inhibiting fatty acid oxidation. Peroxisome proliferator-activated receptor α (PPARα) agonists are often used to treat dyslipidemia in patients, especially in type 2 diabetes. Combinational treatment using a PDK4 inhibitor and PPARα agonists may prove beneficial. However, PPARα agonists may be less effective in the presence of a PDK4 inhibitor because PPARα agonists induce PDK4 expression. In the present study, the effects of clofibric acid, a PPARα agonist, on blood and liver lipids were determined in wild-type and PDK4 knockout mice fed a high-fat diet. As expected, treatment of wild-type mice with clofibric acid resulted in less body weight gain, smaller epididymal fat pads, greater insulin sensitivity, and lower levels of serum and liver triacylglycerol. Surprisingly, rather than decreasing the effectiveness of clofibric acid, PDK4 deficiency enhanced the beneficial effects of clofibric acid on hepatic steatosis, reduced blood glucose levels, and did not prevent the positive effects of clofibric acid on serum triacylglycerols and free fatty acids. The metabolic effects of clofibric acid are therefore independent of the induction of PDK4 expression. The additive beneficial effects on hepatic steatosis may be due to induction of increased capacity for fatty acid oxidation and partial uncoupling of oxidative phosphorylation by clofibric acid, and a reduction in the capacity for fatty acid synthesis as a result of PDK4 deficiency. Journal compilation © 2012 FEBS. No claim to original US government works.

  3. Long-term boron-deficiency-responsive genes revealed by cDNA-AFLP differ between Citrus sinensis roots and leaves

    Science.gov (United States)

    Lu, Yi-Bin; Qi, Yi-Ping; Yang, Lin-Tong; Lee, Jinwook; Guo, Peng; Ye, Xin; Jia, Meng-Yang; Li, Mei-Li; Chen, Li-Song

    2015-01-01

    Seedlings of Citrus sinensis (L.) Osbeck were supplied with boron (B)-deficient (without H3BO3) or -sufficient (10 μM H3BO3) nutrient solution for 15 weeks. We identified 54 (38) and 38 (45) up (down)-regulated cDNA-AFLP bands (transcript-derived fragments, TDFs) from B-deficient leaves and roots, respectively. These TDFs were mainly involved in protein and amino acid metabolism, carbohydrate and energy metabolism, nucleic acid metabolism, cell transport, signal transduction, and stress response and defense. The majority of the differentially expressed TDFs were isolated only from B-deficient roots or leaves, only seven TDFs with the same GenBank ID were isolated from the both. In addition, ATP biosynthesis-related TDFs were induced in B-deficient roots, but unaffected in B-deficient leaves. Most of the differentially expressed TDFs associated with signal transduction and stress defense were down-regulated in roots, but up-regulated in leaves. TDFs related to protein ubiquitination and proteolysis were induced in B-deficient leaves except for one TDF, while only two down-regulated TDFs associated with ubiquitination were detected in B-deficient roots. Thus, many differences existed in long-term B-deficiency-responsive genes between roots and leaves. In conclusion, our findings provided a global picture of the differential responses occurring in B-deficient roots and leaves and revealed new insight into the different adaptive mechanisms of C. sinensis roots and leaves to B-deficiency at the transcriptional level. PMID:26284101

  4. Integration-deficient lentivectors: an effective strategy to purify and differentiate human embryonic stem cell-derived hepatic progenitors.

    Science.gov (United States)

    Yang, Guanghua; Si-Tayeb, Karim; Corbineau, Sébastien; Vernet, Rémi; Gayon, Régis; Dianat, Noushin; Martinet, Clémence; Clay, Denis; Goulinet-Mainot, Sylvie; Tachdjian, Gérard; Tachdjian, Gérard; Burks, Deborah; Vallier, Ludovic; Bouillé, Pascale; Dubart-Kupperschmitt, Anne; Weber, Anne

    2013-07-19

    Human pluripotent stem cells (hPSCs) hold great promise for applications in regenerative medicine. However, the safety of cell therapy using differentiated hPSC derivatives must be improved through methods that will permit the transplantation of homogenous populations of a specific cell type. To date, purification of progenitors and mature cells generated from either embryonic or induced pluripotent stem cells remains challenging with use of conventional methods. We used lentivectors encoding green fluorescent protein (GFP) driven by the liver-specific apoliprotein A-II (APOA-II) promoter to purify human hepatic progenitors. We evaluated both integrating and integration-defective lentivectors in combination with an HIV integrase inhibitor. A human embryonic stem cell line was differentiated into hepatic progenitors using a chemically defined protocol. Subsequently, cells were transduced and sorted at day 16 of differentiation to obtain a cell population enriched in hepatic progenitor cells. After sorting, more than 99% of these APOA-II-GFP-positive cells expressed hepatoblast markers such as α-fetoprotein and cytokeratin 19. When further cultured for 16 days, these cells underwent differentiation into more mature cells and exhibited hepatocyte properties such as albumin secretion. Moreover, they were devoid of vector DNA integration. We have developed an effective strategy to purify human hepatic cells from cultures of differentiating hPSCs, producing a novel tool that could be used not only for cell therapy but also for in vitro applications such as drug screening. The present strategy should also be suitable for the purification of a broad range of cell types derived from either pluripotent or adult stem cells.

  5. Molecular characterization of hepatitis B virus in Bangladesh reveals a highly recombinant population.

    Directory of Open Access Journals (Sweden)

    Saif Ullah Munshi

    Full Text Available The natural history and treatment outcome of hepatitis B viruses (HBV infection is largely dependent on genotype, subgenotype, and the presence or absence of virulence associated mutations. We have studied the prevalence of genotype and subgenotype as well as virulence and drug resistance associated mutations and prevalence of recombinant among HBV from Bangladesh. A prospective cross-sectional study was conducted among treatment naïve chronic HBV patients attending at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh for HBV viral load assessment between June and August 2015. Systematical selected 50% of HBV DNA positive patients (every second patient were enrolled. Biochemical and serological markers for HBV infection and whole genome sequencing (WGS was performed on virus positive sample. Genotype, subgenotype, virulence, nucleos(tide analogue (NA resistance (NAr mutations, and the prevalence of recombinant isolates were determined. Among 114 HBV DNA positive patients, 57 were enrolled in the study and 53 HBV WGS were generated for downstream analysis. Overall, 38% (22/57 and 62% (35/57 of patients had acute and chronic HBV infections, respectively. The prevalence of genotypes A, C, and D was 18.9% (10/53, 45.3% (24/53, and 35.8% (19/53, respectively. Among genotype A, C and D isolates subgenotype A1 (90%; 9/10, C1 (87.5%; 21/24 and D2 (78.9%; 15/19 predominates. The acute infection, virulence associated mutations, and viral load was higher in the genotype D isolates. Evidence of recombination was identified in 22.6% (12/53 of the HBV isolates including 20.0% (2/10, and 16.7% (4/24 and 31.6% (6/19 of genotype A, C and D isolates, respectively. The prevalence of recombination was higher in chronic HVB patients (32.2%; 10/31 versus 9.1%; 2/22; p<0.05. NAr mutations were identified in 47.2% (25/53 of the isolates including 33.9% novel mutations (18/53. HBV genotype C and D predominated in this population in Bangladesh; a

  6. Chronic hepatitis

    African Journals Online (AJOL)

    infection by four diagnostic systems: first generation and second generation. ELlSA, second generation recombinant immunoblot assay and nested polymerase chain reaction analysis. HepatoJogy 1992; 16: 300-305. 14. Van der Poel CL, ... Alpha-1-antitrypsin deficiency. Alcoholic hepatitis. Non-alcoholic steatohepatitis.

  7. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Lipase Deficiency Liver Cancer Liver Cysts Non-Alcoholic Fatty Liver Disease Primary Biliary Cholangitis Primary Sclerosing Cholangitis What ... B & C Alcohol-related Liver Disease Non-alcoholic Fatty Liver Disease (NAFLD) & Non-alcoholic Steatohepatitis (NASH) Autoimmune Hepatitis ...

  8. Knockdown expression and hepatic deficiency reveal anatheroprotective role for SR-BI in liver and peripheral tissues

    Energy Technology Data Exchange (ETDEWEB)

    Huby, Thierry; Doucet, Chantal; Dachet, Christiane; Ouzilleau,Betty; Ueda, Yukihiko; Afzal, Veena; Rubin, Edward; Chapman, M. John; Lesnik, Philippe

    2006-07-18

    Scavenger receptor SR-BI has been implicated inHDL-dependent atheroprotective mechanisms. We report the generation of anSR-BI conditional knockout mouse model in which SR-BI gene targeting byloxP site insertion produced a hypomorphic allele (hypomSR-BI).Attenuated SR-BI expression in hypomSR-BI mice resulted in 2-foldelevation in plasma total cholesterol (TC) levels. Cre-mediated SR-BIgene inactivation of the hypomorphic SR-BI allele in hepatocytes(hypomSR-BI-KOliver) was associated with high plasma TC concentrations,increased plasma free cholesterol/TC (FC/TC) ratio, and alipoprotein-cholesterol profile typical of SR-BI-/- mice. Plasma TClevels were increased 2-fold in hypomSR-BI and control mice fed anatherogenic diet, whereas hypomSR-BI-KOliver and SR-BI-/- mice developedsevere hypercholesterolemia due to accumulation of FC-rich, VLDL-sizedparticles. Atherosclerosis in hypomSR-BI mice was enhanced (2.5-fold)compared with that in controls, but to a much lower degree than inhypomSR-BI-KOliver (32-fold) and SR-BI-/- (48-fold) mice. The lattermodels did not differ in either plasma lipid levels or in the capacity ofVLDL-sized lipoproteins to induce macrophage cholesterol loading.However, reduced atherosclerosis in hypomSR-BI-KOliver mice wasassociated with decreased lesional macrophage content as compared withthat in SR-BI-/- mice. These data imply that, in addition to its majoratheroprotective role in liver, SR-BI may exert an antiatherogenic rolein extrahepatic tissues.

  9. Tumor features and correlation between lymphocyte count and biochemical parameters in patients with hepatitis B virus-associated primary liver cancer with Yin deficiency

    Directory of Open Access Journals (Sweden)

    YANG Zhiyun

    2016-03-01

    Full Text Available ObjectiveTo investigate the tumor features and the correlation between lymphocyte count and biochemical parameters in patients with hepatitis B virus-associated primary liver cancer (PLC with yin deficiency. MethodsA total of 148 PLC patients who were treated in Beijing Ditan Hospital, Capital Medical University, from July 2013 to February 2015 were enrolled and divided into yin-deficiency PLC group (52 patients and non-yin-deficiency PLC group (96 patients. The patients′ general information and laboratory markers were collected, including oncological parameters (alpha-fetoprotein, carcinoembryonic antigen (CEA, and carbohydrate antigen 199 (CA19-9, virological parameter (HBsAg, gross type (nodular type, massive type, bulky type, and diffuse type, radiological features (main portal vein diameter, portal vein tumor thrombus, and extrahepatic metastasis, biochemical parameters (Model for End-Stage Liver Disease (MELD score, white blood cell, red blood cell, platelet (PLT, alanine aminotransferase, aspartate aminotransferase, total bilirubin (TBil, gamma-glutamyl transpeptidase, alkaline phosphatase, albumin, cholinesterase, prothrombin time (PT, and prothrombin time activity (PTA, and lymphocyte count. The t-test was applied for comparison of normally distributed continuous data between groups, and the Pearson correlation analysis was applied for correlation analysis. The Mann-Whitney U test was applied for comparison of non-normally distributed continuous data between groups, and the Spearman correlation analysis was applied for correlation analysis. The chi-square test was applied for comparison of categorical data between groups. ResultsHBsAg showed a significant difference between the two groups (χ2=5.658, P=0.017. Compared with the non-yin-deficiency PLC group, the yin-deficiency PLC group had significantly increased CEA and CA19-9 (U=-2.200 and -2.194, both P<0.05, significantly increased MELD score, TBil, and PT (t=2.2, U=-2.0, U=-2

  10. Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

    Science.gov (United States)

    Berenguer, Juan; Rodríguez-Castellano, Elena; Carrero, Ana; Von Wichmann, Miguel A; Montero, Marta; Galindo, María J; Mallolas, Josep; Crespo, Manuel; Téllez, María J; Quereda, Carmen; Sanz, José; Barros, Carlos; Tural, Cristina; Santos, Ignacio; Pulido, Federico; Guardiola, Josep M; Rubio, Rafael; Ortega, Enrique; Montes, María L; Jusdado, Juan J; Gaspar, Gabriel; Esteban, Herminia; Bellón, José M; González-García, Juan

    2017-08-01

    We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4 + T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

  11. Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

    Science.gov (United States)

    Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

    2016-10-03

    FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

  12. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ...

  13. Transcriptome analyses of a salt-tolerant cytokinin-deficient mutant reveal differential regulation of salt stress response by cytokinin deficiency.

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    Rie Nishiyama

    Full Text Available Soil destruction by abiotic environmental conditions, such as high salinity, has resulted in dramatic losses of arable land, giving rise to the need of studying mechanisms of plant adaptation to salt stress aimed at creating salt-tolerant plants. Recently, it has been reported that cytokinins (CKs regulate plant environmental stress responses through two-component systems. A decrease in endogenous CK levels could enhance salt and drought stress tolerance. Here, we have investigated the global transcriptional change caused by a reduction in endogenous CK content under both normal and salt stress conditions. Ten-day-old Arabidopsis thaliana wild-type (WT and CK-deficient ipt1,3,5,7 plants were transferred to agar plates containing either 0 mM (control or 200 mM NaCl and maintained at normal growth conditions for 24 h. Our experimental design allowed us to compare transcriptome changes under four conditions: WT-200 mM vs. WT-0 mM, ipt1,3,5,7-0 mM vs. WT-0 mM, ipt1,3,5,7-200 mM vs. ipt1,3,5,7-0 mM and ipt1,3,5,7-200 mM vs. WT-200 mM NaCl. Our results indicated that the expression of more than 10% of all of the annotated Arabidopsis genes was altered by CK deficiency under either normal or salt stress conditions when compared to WT. We found that upregulated expression of many genes encoding either regulatory proteins, such as NAC, DREB and ZFHD transcription factors and the calcium sensor SOS3, or functional proteins, such as late embryogenesis-abundant proteins, xyloglucan endo-transglycosylases, glycosyltransferases, glycoside hydrolases, defensins and glyoxalase I family proteins, may contribute to improved salt tolerance of CK-deficient plants. We also demonstrated that the downregulation of photosynthesis-related genes and the upregulation of several NAC genes may cause the altered morphological phenotype of CK-deficient plants. This study highlights the impact of CK regulation on the well-known stress-responsive signaling pathways, which

  14. Switch junction sequences in PMS2-deficient mice reveal a microhomology-mediated mechanism of Ig class switch recombination

    Science.gov (United States)

    Ehrenstein, Michael R.; Rada, Cristina; Jones, Anne-Marie; Milstein, César; Neuberger, Michael S.

    2001-01-01

    Isotype switching involves a region-specific, nonhomologous recombinational deletion that has been suggested to occur by nonhomologous joining of broken DNA ends. Here, we find increased donor/acceptor homology at switch junctions from PMS2-deficient mice and propose that class switching can occur by microhomology-mediated end-joining. Interestingly, although isotype switching and somatic hypermutation show many parallels, we confirm that PMS2 deficiency has no major effect on the pattern of nucleotide substitutions generated during somatic hypermutation. This finding is in contrast to MSH2 deficiency. With MSH2, the altered pattern of switch recombination and hypermutation suggests parallels in the mechanics of the two processes, whereas the fact that PMS2 deficiency affects only switch recombination may reflect differences in the pathways of break resolution. PMID:11717399

  15. Sensory Neuronopathy Revealing Severe Vitamin B12 Deficiency in a Patient with Anorexia Nervosa: An Often-Forgotten Reversible Cause

    Directory of Open Access Journals (Sweden)

    Jérôme Franques

    2017-03-01

    Full Text Available Vitamin B12 (B12 deficiency is known to be associated with various neurological manifestations. Although central manifestations such as dementia or subacute combined degeneration are the most classic, neurological manifestations also include sensory neuropathies. However, B12 deficiency is still rarely integrated as a potential cause of sensory neuronopathy. Moreover, as many medical conditions can falsely normalize serum B12 levels even in the context of a real B12 deficiency, some cases may easily remain underdiagnosed. We report the illustrating case of an anorexic patient with sensory neuronopathy and consistently normal serum B12 levels. After all classical causes of sensory neuronopathy were ruled out, her clinical and electrophysiological conditions first worsened after folate administration, but finally improved dramatically after B12 administration. B12 deficiency should be systematically part of the etiologic workup of sensory neuronopathy, especially in a high risk context such as anorexia nervosa.

  16. Urinary Hepcidin Levels in Iron-Deficient and Iron-Supplemented Piglets Correlate with Hepcidin Hepatic mRNA and Serum Levels and with Body Iron Status.

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    Robert Staroń

    Full Text Available Among livestock, domestic pig (Sus scrofa is a species, in which iron metabolism has been most intensively examined during last decade. The obvious reason for studying the regulation of iron homeostasis especially in young pigs is neonatal iron deficiency anemia commonly occurring in these animals. Moreover, supplementation of essentially all commercially reared piglets with iron entails a need for monitoring the efficacy of this routine practice followed in the swine industry for several decades. Since the discovery of hepcidin many studies confirmed its role as key regulator of iron metabolism and pointed out the assessment of its concentrations in biological fluids as diagnostic tool for iron-related disorder. Here we demonstrate that urine hepcidin-25 levels measured by a combination of weak cation exchange chromatography and time-of-flight mass spectrometry (WCX-TOF MS are highly correlated with mRNA hepcidin expression in the liver and plasma hepcidin-25 concentrations in anemic and iron-supplemented 28-day old piglets. We also found a high correlation between urine hepcidin level and hepatic non-heme iron content. Our results show that similarly to previously described transgenic mouse models of iron disorders, young pigs constitute a convenient animal model to explore accuracy and relationship between indicators for assessing systemic iron status.

  17. Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.

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    João A Paredes

    Full Text Available Loss of thymidine kinase 2 (TK2 causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA depletion syndrome (MDS in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue.

  18. Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.

    Science.gov (United States)

    Paredes, João A; Zhou, Xiaoshan; Höglund, Stefan; Karlsson, Anna

    2013-01-01

    Loss of thymidine kinase 2 (TK2) causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA) depletion syndrome (MDS) in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue.

  19. Longitudinal Study of Hepatitis A Infection by Saliva Sampling: The Kinetics of HAV Markers in Saliva Revealed the Application of Saliva Tests for Hepatitis A Study

    Science.gov (United States)

    Amado Leon, Luciane Almeida; de Almeida, Adilson José; de Paula, Vanessa Salete; Tourinho, Renata Santos; Villela, Daniel Antunes Maciel; Gaspar, Ana Maria Coimbra; Lewis-Ximenez, Lia Laura; Pinto, Marcelo Alves

    2015-01-01

    Despite the increasing numbers of studies investigating hepatitis A diagnostic through saliva, the frequency and the pattern of hepatitis A virus (HAV) markers in this fluid still remains unknown. To address this issue, we carried on a longitudinal study to examine the kinetics of HAV markers in saliva, in comparison with serum samples. The present study followed-up ten patients with acute hepatitis A infection during 180 days post diagnosis (dpd). Total anti-HAV was detected in paired serum and saliva samples until the end of the follow-up, showing a peak titer at 90th. However, total anti-HAV level was higher in serum than in saliva samples. This HAV marker showed a probability of 100% to be detected in both serum and saliva during 180 dpd. The IgM anti-HAV could be detected in saliva up to 150 dpd, showing the highest frequency at 30th, when it was detected in all individuals. During the first month of HAV infection, this acute HAV marker showed a detection probability of 100% in paired samples. The detection of IgM anti-HAV in saliva was not dependent on its level in serum, HAV-RNA detection and/or viral load, since no association was found between IgM anti-HAV positivity in saliva and any of these parameter (p>0.05). Most of the patients (80%) were found to contain HAV-RNA in saliva, mainly at early acute phase (30th day). However, it was possible to demonstrate the HAV RNA presence in paired samples for more than 90 days, even after seroconversion. No significant relationship was observed between salivary HAV-RNA positivity and serum viral load, demonstrating that serum viral load is not predictive of HAV-RNA detection in saliva. Similar viral load was seen in paired samples (on average 104 copies/mL). These data demonstrate that the best diagnostic coverage can be achieved by salivary anti-HAV antibodies and HAV-RNA tests during 30–90 dpd. The long detection and high probability of specific-HAV antibodies positivity in saliva samples make the assessment of

  20. An RNA-Seq transcriptome analysis of orthophosphate-deficient white lupin reveals novel insights into phosphorus acclimation in plants.

    Science.gov (United States)

    O'Rourke, Jamie A; Yang, S Samuel; Miller, Susan S; Bucciarelli, Bruna; Liu, Junqi; Rydeen, Ariel; Bozsoki, Zoltan; Uhde-Stone, Claudia; Tu, Zheng Jin; Allan, Deborah; Gronwald, John W; Vance, Carroll P

    2013-02-01

    Phosphorus, in its orthophosphate form (P(i)), is one of the most limiting macronutrients in soils for plant growth and development. However, the whole-genome molecular mechanisms contributing to plant acclimation to P(i) deficiency remain largely unknown. White lupin (Lupinus albus) has evolved unique adaptations for growth in P(i)-deficient soils, including the development of cluster roots to increase root surface area. In this study, we utilized RNA-Seq technology to assess global gene expression in white lupin cluster roots, normal roots, and leaves in response to P(i) supply. We de novo assembled 277,224,180 Illumina reads from 12 complementary DNA libraries to build what is to our knowledge the first white lupin gene index (LAGI 1.0). This index contains 125,821 unique sequences with an average length of 1,155 bp. Of these sequences, 50,734 were transcriptionally active (reads per kilobase per million reads ≥ 3), representing approximately 7.8% of the white lupin genome, using the predicted genome size of Lupinus angustifolius as a reference. We identified a total of 2,128 sequences differentially expressed in response to P(i) deficiency with a 2-fold or greater change and P ≤ 0.05. Twelve sequences were consistently differentially expressed due to P(i) deficiency stress in three species, Arabidopsis (Arabidopsis thaliana), potato (Solanum tuberosum), and white lupin, making them ideal candidates to monitor the P(i) status of plants. Additionally, classic physiological experiments were coupled with RNA-Seq data to examine the role of cytokinin and gibberellic acid in P(i) deficiency-induced cluster root development. This global gene expression analysis provides new insights into the biochemical and molecular mechanisms involved in the acclimation to P(i) deficiency.

  1. Liver failure with coagulopathy, hyperammonemia and cyclic vomiting in a toddler revealed to have combined heterozygosity for genes involved with ornithine transcarbamylase deficiency and Wilson disease.

    Science.gov (United States)

    Mira, Valerie; Boles, Richard G

    2012-01-01

    A girl with a 2 month history of cyclic episodes of vomiting, diarrhea, and lethargy lasting 2-3 days each presented with acute hepatopathy (ALT 3,500 IU/L) with coagulopathy (PT 55 s) and hyperammonemia (207 μmol/L) at age 1½ years. Biochemical and molecular analyzes revealed ornithine transcarbamylase (OTC) deficiency. While laboratory signs of mild hepatocellular dysfunction are common in OTC deficiency, substantial liver failure with coagulopathy is generally not seen, although four others cases have been reported, three of which presented with cyclic vomiting. Further evaluation in our case revealed elevated urine (198.8 μg/g creatinine) and liver (103 μg/g dry weight) copper content, and a heterozygous mutation in the Wilson disease gene, ATP7B. Our patient, now aged 5 years, has remained in excellent health with normal growth and development on fasting avoidance, a modified vegan diet, and sodium phenylbutyrate.These five cases demonstrate that generalized liver dysfunction/failure is a potential serious complication of OTC deficiency, although not a common one, and suggests that an ALT and PT should be obtained in OTC patients during episodes of hyperammonemia. Cyclic vomiting is a known presentation of OTC deficiency; it is not known if comorbid liver failure predisposes toward this phenotype. We propose that the heterozygote state in ATP7B increases the liver copper content, thus predisposing our patient with OTC deficiency to develop liver failure during a hyperammonemic episode. Our present case is an example of the opportunity of molecular diagnostics to identify putative modifier genes in patients with atypical presentations of genetic disorders.

  2. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    Energy Technology Data Exchange (ETDEWEB)

    Kaphalia, Lata [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Boroumand, Nahal [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Hyunsu, Ju [Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Calhoun, William J. [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States)

    2014-06-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

  3. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    International Nuclear Information System (INIS)

    Kaphalia, Lata; Boroumand, Nahal; Hyunsu, Ju; Kaphalia, Bhupendra S.; Calhoun, William J.

    2014-01-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

  4. Magnetic resonance imaging reveals altered distribution of hepatic fat in children with type 1 diabetes compared to controls.

    Science.gov (United States)

    Regnell, Simon E; Peterson, Pernilla; Trinh, Lena; Broberg, Per; Leander, Peter; Lernmark, Åke; Månsson, Sven; Elding Larsson, Helena

    2015-08-01

    Children with type 1 diabetes have been identified as a risk group for non-alcoholic fatty liver disease (NAFLD). The aim was to compare total hepatic fat fraction and fat distribution across Couinaud segments in children with type 1 diabetes and controls and the relation of hepatic fat to plasma and anthropometric parameters. Hepatic fat fraction and fat distribution across Couinaud segments were measured with magnetic resonance imaging (MRI) in 22 children with type 1 diabetes and 32 controls. Blood tests and anthropometric data were collected. No children had NAFLD. Children with type 1 diabetes had a slightly lower hepatic fat fraction (median 1.3%) than controls (median 1.8%), and their fat had a different segmental distribution. The fat fraction of segment V was the most representative of the liver as a whole. An incidental finding was that diabetes patients treated with multiple daily injections of insulin (MDI) had a fat distribution more similar to controls than patients with continuous subcutaneous insulin infusion (CSII). In children with type 1 diabetes, NAFLD may be less common than recent studies have suggested. Children with type 1 diabetes may have a lower fat fraction and a different fat distribution in the liver than controls. Diabetes treatment with MDI or CSII may affect liver fat, but this needs to be confirmed in a larger sample of patients. The heterogeneity of hepatic fat infiltration may affect results when liver biopsy is used for diagnosing fatty liver. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Standardized Salvia miltiorrhiza Extract Suppresses Hepatic Stellate Cell Activation and Attenuates Steatohepatitis Induced by a Methionine-Choline Deficient Diet in Mice

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    Hak Sung Lee

    2014-06-01

    Full Text Available The aim of this study was to examine the effect of standardized extract of Salvia miltiorrhiza (SME on gene and protein expression of non-alcoholic steatohepatitis (NASH-related factors in activated human hepatic stellate cells (HSC, and in mice with steatohepatitis induced by a methionine-choline deficient (MCD diet. Male C57BL/6J mice were placed on an MCD or control diet for 8 weeks and SME (0, 0.1, 0.5 and 1 mg/kg body weight was administered orally every other day for 4 or 6 weeks. HSCs from the LX-2 cell line were treated with transforming growth factor β-1 (TGF-β1 or TGF-β1 plus SME (0.1–10 μg/mL. To investigate the effect of SME on reactive oxygen species (ROS-induced condition, LX-2 cells were treated with hydrogen peroxide (H2O2 or H2O2 plus SME (0.1–100 μg/mL. MCD administration for 12 weeks increased mRNA expression of tumor necrosis factor (TNF-α, TGF-β1, interleukin-1β (IL-1β, C-reactive protein (CRP, α-smooth muscle actin (α-SMA, type I collagen, matrix metalloproteinase-2 (MMP-2 and MMP-9. TGF-β1-induced LX-2 cells exhibited similar gene expression patterns. SME treatment significantly reduced the mRNA and protein expression of NASH-related factors in the mouse model and HSCs. Histopathological liver analysis showed improved non-alcoholic fatty liver disease (NAFLD activity and fibrosis score in SME-treated mice. The in vivo studies showed that SME had a significant effect at low doses. These results suggest that SME might be a potential therapeutic candidate for NAFLD treatment.

  6. A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging.

    Science.gov (United States)

    Baroncelli, Laura; Molinaro, Angelo; Cacciante, Francesco; Alessandrì, Maria Grazia; Napoli, Debora; Putignano, Elena; Tola, Jonida; Leuzzi, Vincenzo; Cioni, Giovanni; Pizzorusso, Tommaso

    2016-10-01

    Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and autistic-like behavioural disturbances, language and speech impairment. Since no data are available about the neural and molecular underpinnings of this disease, we performed a longitudinal analysis of behavioural and pathological alterations associated with CrT deficiency in a CCDS1 mouse model. We found precocious cognitive and autistic-like defects, mimicking the early key features of human CCDS1. Moreover, mutant mice displayed a progressive impairment of short and long-term declarative memory denoting an early brain aging. Pathological examination showed a prominent loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and the accumulation of autofluorescent lipofuscin. Our data suggest that brain Cr depletion causes both early intellectual disability and late progressive cognitive decline, and identify novel targets to design intervention strategies aimed at overcoming brain CCDS1 alterations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Histidine augments the suppression of hepatic glucose production by central insulin action.

    Science.gov (United States)

    Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-Ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime; Kaneko, Shuichi; Kasuga, Masato; Inoue, Hiroshi

    2013-07-01

    Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H1 receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H1 receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes.

  8. Two novel cases of cerebral haemorrhages at the neonatal period associated with inherited factor VII deficiency, one of them revealing a new nonsense mutation (Ser52Stop).

    Science.gov (United States)

    Giansily-Blaizot, Muriel; Aguilar-Martinez, Patricia; Briquel, Marie-Elisabeth; d'Oiron, Roseline; De Maistre, Emmanuel; Epelbaum, Serge; Schved, Jean-François

    2003-02-01

    Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.

  9. Short alleles revealed by PCR demonstrate no heterozygote deficiency at minisatellite loci D1S7, D7S21, and D12S11

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, S.; Castro, A.; Fernandez-Fernandez, I.; Pancorbo, M.M. de [Universidad del Pais Vasco, Vizcaya (Spain)

    1997-02-01

    Short VNTR alleles that go undetected after conventional Southern blot hybridization may constitute an alternative explanation for the heterozygosity deficiency observed at some minisatellite loci. To examine this hypothesis, we have employed a screening procedure based on PCR amplification of those individuals classified as homozygotes in our databases for the loci D1S7, D7S21, and D12S11. The results obtained indicate that the frequency of these short alleles is related to the heterozygosity deficiency observed. For the most polymorphic locus, D1S7, {approximately}60% of those individuals previously classified as homozygotes were in fact heterozygotes for a short allele. After the inclusion of these new alleles, the agreement between observed and expected heterozygosity, along with other statistical tests employed, provide additional evidence for lack of population substructuring. Comparisons of allele frequency distributions reveal greater differences between racial groups than between closely related populations. 45 refs., 3 figs., 6 tabs.

  10. Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice.

    Science.gov (United States)

    Xia, Bo; Cai, Guo He; Yang, Hao; Wang, Shu Pei; Mitchell, Grant A; Wu, Jiang Wei

    2017-12-01

    Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency.

  11. Hepatitis C

    Science.gov (United States)

    ... Workshops Follow Us Home Health Information Liver Disease Hepatitis (Viral) Hepatitis C Related Topics English English Español Section Navigation Hepatitis (Viral) What Is Viral Hepatitis? Hepatitis A Hepatitis B ...

  12. Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice.

    Science.gov (United States)

    Pardo, Marta; Cheng, Yuyan; Velmeshev, Dmitry; Magistri, Marco; Eldar-Finkelman, Hagit; Martinez, Ana; Faghihi, Mohammad A; Jope, Richard S; Beurel, Eleonore

    2017-03-23

    Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA- or HDAC4 siRNA-induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1 -/- mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets.

  13. Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes

    DEFF Research Database (Denmark)

    Winther, Thilde Nordmann; Jacobsen, Kari Stougaard; Mirza, Aashiq Hussain

    2014-01-01

    Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role...... in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes. Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children...... with chronic hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBe...

  14. Expression of an IRF-3 fusion protein and mouse estrogen receptor, inhibits hepatitis C viral replication in RIG-I-deficient Huh 7.5 cells

    Directory of Open Access Journals (Sweden)

    Liu Chen

    2011-09-01

    Full Text Available Abstract Interferon Regulatory Factor-3 (IRF-3 plays a central role in the induction of interferon (IFN production and succeeding interferon-stimulated genes (ISG expression en route for restraining hepatitis C virus (HCV infection. Here, we established a stable Huh7.5-IRF3ER cell line expressing a fusion protein of IRF-3 and mouse estrogen receptor (ER to examine IFN production and anti-HCV effects of IRF-3 in retinoic acid inducible-gene-I (RIG-I deficient Huh 7.5 cells. Homodimerization of the IRF-3ER fusion protein was detected by Western blotting after treatment with the estrogen receptor agonist 4-hydrotamoxifen (4-HT in Huh7.5-IRF3ER cells. Expression of IFN-α, IFN-β, and their inhibitory effects on HCV replication were demonstrated by real-time polymerase chain reaction (PCR. Peak expression of IFN-α and IFN-β was achieved 24-hours post 4-HT treatment, coinciding with the appearance of phosphorylated signal transducer and activator of transcription (STAT proteins. Additionally, HCV viral replication declined in time-dependent fashion. In previous studies, a novel IFN-mediated pathway regulating expression of 1-8U and heterogeneous nuclear ribonucleoprotein M (hnRNP M inhibited HCV internal ribosomal entry site (IRES-dependent translation. When expression of ISGs such as 1-8U and hnRNP M were measured in 4-HT-treated Huh7.5-IRF3ER cells, both genes were positively regulated by activation of the IRF-3ER fusion protein. In conclusion, the anti-HCV effects of IRF-3ER homodimerization inhibited HCV RNA replication as well as HCV IRES-dependent translation in Huh7.5-IRF3ER cells. The results of this study indicate that IRF-3ER homodimerization is a key step to restore IFN expression in Huh7.5-IRF3ER cells and in achieving its anti-HCV effects.

  15. CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice

    Directory of Open Access Journals (Sweden)

    Crockett Elahé T

    2007-05-01

    Full Text Available Abstract Background Neutrophil adhesion and migration are critical in hepatic ischemia and reperfusion injury (I/R. P-selectin and the intercellular adhesion molecule (ICAM-1 can mediate neutrophil-endothelial cell interactions, neutrophil migration, and the interactions of neutrophils with hepatocytes in the liver. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury, indicating that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the aim of this study was to assess the role of P-selectin and ICAM-1 in neutrophil infiltration and liver injury during early and late phases of liver I/R. Methods Adult male wild-type and P-selectin/ICAM-1-deficient (P/I null mice underwent 90 minutes of partial liver ischemia followed by various periods of reperfusion (6, 15 h, and a survival study. Liver injury was assessed by plasma level of alanine aminotransferase (ALT and histopathology. The plasma cytokines, TNF-α, IL-6, MIP-2 and KC, were measured by ELISA. Results Reperfusion caused significant hepatocellular injury in both wild-type and P/I null mice as was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil infiltration into the ischemic livers of both wild-type and P/I null mice. Although the levels of ALT and neutrophil infiltration were slightly lower in the P/I null mice compared with the wild-type mice the differences were not statistically significant. The plasma cytokine data of TNF-α and IL-6 followed a similar pattern to ALT data, and no significant difference was found between the wild-type and P/I null groups. In contrast, a significant difference in KC and MIP-2 chemokine levels was observed between the wild-type and P/I null mice. Additionally, the survival study showed a trend towards increased survival in the P/I null group. Conclusion While ICAM-1 and P

  16. A zebrafish model of congenital disorders of glycosylation with phosphomannose isomerase deficiency reveals an early opportunity for corrective mannose supplementation

    Directory of Open Access Journals (Sweden)

    Jaime Chu

    2013-01-01

    Individuals with congenital disorders of glycosylation (CDG have recessive mutations in genes required for protein N-glycosylation, resulting in multi-systemic disease. Despite the well-characterized biochemical consequences in these individuals, the underlying cellular defects that contribute to CDG are not well understood. Synthesis of the lipid-linked oligosaccharide (LLO, which serves as the sugar donor for the N-glycosylation of secretory proteins, requires conversion of fructose-6-phosphate to mannose-6-phosphate via the phosphomannose isomerase (MPI enzyme. Individuals who are deficient in MPI present with bleeding, diarrhea, edema, gastrointestinal bleeding and liver fibrosis. MPI-CDG patients can be treated with oral mannose supplements, which is converted to mannose-6-phosphate through a minor complementary metabolic pathway, restoring protein glycosylation and ameliorating most symptoms, although liver disease continues to progress. Because Mpi deletion in mice causes early embryonic lethality and thus is difficult to study, we used zebrafish to establish a model of MPI-CDG. We used a morpholino to block mpi mRNA translation and established a concentration that consistently yielded 13% residual Mpi enzyme activity at 4 days post-fertilization (dpf, which is within the range of MPI activity detected in fibroblasts from MPI-CDG patients. Fluorophore-assisted carbohydrate electrophoresis detected decreased LLO and N-glycans in mpi morphants. These deficiencies resulted in 50% embryonic lethality by 4 dpf. Multi-systemic abnormalities, including small eyes, dysmorphic jaws, pericardial edema, a small liver and curled tails, occurred in 82% of the surviving larvae. Importantly, these phenotypes could be rescued with mannose supplementation. Thus, parallel processes in fish and humans contribute to the phenotypes caused by Mpi depletion. Interestingly, mannose was only effective if provided prior to 24 hpf. These data provide insight into treatment efficacy

  17. Comprehensive Analysis of CD8+-T-Cell Responses against Hepatitis C Virus Reveals Multiple Unpredicted Specificities

    OpenAIRE

    Lauer, Georg M.; Ouchi, Kei; Chung, Raymond T.; Nguyen, Tam N.; Day, Cheryl L.; Purkis, Deborah R.; Reiser, Markus; Kim, Arthur Y.; Lucas, Michaela; Klenerman, Paul; Walker, Bruce D.

    2002-01-01

    The hepatitis C virus (HCV)-specific CD8+-T-cell response is thought to play a critical role in HCV infection. Studies of these responses have largely relied on the analysis of a small number of previously described or predicted HCV epitopes, mostly restricted by HLA A2. In order to determine the actual breadth and magnitude of CD8+-T-cell responses in the context of diverse HLA class I alleles, we performed a comprehensive analysis of responses to all expressed HCV proteins. By using a panel...

  18. Small RNA profiling reveals phosphorus deficiency as a contributing factor in symptom expression for citrus huanglongbing disease.

    Science.gov (United States)

    Zhao, Hongwei; Sun, Ruobai; Albrecht, Ute; Padmanabhan, Chellappan; Wang, Airong; Coffey, Michael D; Girke, Thomas; Wang, Zonghua; Close, Timothy J; Roose, Mikeal; Yokomi, Raymond K; Folimonova, Svetlana; Vidalakis, Georgios; Rouse, Robert; Bowman, Kim D; Jin, Hailing

    2013-03-01

    Huanglongbing (HLB) is a devastating citrus disease that is associated with bacteria of the genus 'Candidatus Liberibacter' (Ca. L.). Powerful diagnostic tools and management strategies are desired to control HLB. Host small RNAs (sRNA) play a vital role in regulating host responses to pathogen infection and are used as early diagnostic markers for many human diseases, including cancers. To determine whether citrus sRNAs regulate host responses to HLB, sRNAs were profiled from Citrus sinensis 10 and 14 weeks post grafting with Ca. L. asiaticus (Las)-positive or healthy tissue. Ten new microRNAs (miRNAs), 76 conserved miRNAs, and many small interfering RNAs (siRNAs) were discovered. Several miRNAs and siRNAs were highly induced by Las infection, and can be potentially developed into early diagnosis markers of HLB. miR399, which is induced by phosphorus starvation in other plant species, was induced specifically by infection of Las but not Spiroplasma citri that causes citrus stubborn-a disease with symptoms similar to HLB. We found a 35% reduction of phosphorus in Las-positive citrus trees compared to healthy trees. Applying phosphorus oxyanion solutions to HLB-positive sweet orange trees reduced HLB symptom severity and significantly improved fruit production during a 3-year field trial in south-west Florida. Our molecular, physiological, and field data suggest that phosphorus deficiency is linked to HLB disease symptomology.

  19. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns ... are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty Liver ...

  20. ACL deficient potential copers and non-copers reveal different isokinetic quadriceps strength profiles in the early stage after injury

    Science.gov (United States)

    Eitzen, I; Eitzen, TJ; Holm, I; Snyder-Mackler, L; Risberg, MA

    2011-01-01

    Background Isokinetic muscle strength tests using the peak torque value is the most frequently included quadriceps muscle strength measurement for anterior cruciate ligament (ACL) injured subjects. Aims The purpose of this study was to investigate quadriceps muscle performance during the whole isokinetic curve in ACL deficient subjects classified as potential copers or non-copers, and investigate whether these curve profiles were associated with single-leg hop performance. We hypothesized that quadriceps muscle torque at other knee flexion angles than peak torque would give more information about quadriceps muscle strength deficits. Furthermore, we hypothesized that there would be significant torque differences between potential copers and non-copers, and a significant relationship between angle specific torque values and single-leg hop performance. Study Design Cross-sectional study; Level of evidence, 2 Methods Seventy-six individuals with a complete unilateral ACL rupture within the last 3 months were included. The subjects were classified into potential copers and non-copers according to the criteria from Fitzgerald et al12. Isokinetic quadriceps muscle tests were performed at 60°/sec (Biodex 6000). Mean torque values were calculated for peak torque as well as for specific knee flexion angles. The one-leg hop and the 6 meter timed hop tests were included and symmetry indices were used. Results The peak torque value did not identify the largest quadriceps muscle strength deficit. Rather, these were established at knee flexion angles of less than 40°. There were significant differences in angle specific torque values between potential copers and non-copers (p<0.05). Moderate to strong associations were disclosed between angle specific torque values and single-leg hop performance, but only for non-copers (r≥0.32– 0.58). Conclusions Angle specific quadriceps muscle torque values of less than 40° of knee flexion provide more information on the quadriceps

  1. RNAi screen reveals a role of SPHK2 in dengue virus-mediated apoptosis in hepatic cell lines.

    Directory of Open Access Journals (Sweden)

    Atthapan Morchang

    Full Text Available Hepatic dysfunction is a feature of dengue virus (DENV infection. Hepatic biopsy specimens obtained from fatal cases of DENV infection show apoptosis, which relates to the pathogenesis of DENV infection. However, how DENV induced liver injury is not fully understood. In this study, we aim to identify the factors that influence cell death by employing an apoptosis-related siRNA library screening. Our results show the effect of 558 gene silencing on caspase 3-mediated apoptosis in DENV-infected Huh7 cells. The majority of genes that contributed to apoptosis were the apoptosis-related kinase enzymes. Tumor necrosis factor superfamily member 12 (TNFSF12, and sphingosine kinase 2 (SPHK2, were selected as the candidate genes to further validate their influences on DENV-induced apoptosis. Transfection of siRNA targeting SPHK2 but not TNFSF12 genes reduced apoptosis determined by Annexin V/PI staining. Knockdown of SPHK2 did not reduce caspase 8 activity; however, did significantly reduce caspase 9 activity, suggesting its involvement of SPHK2 in the intrinsic pathway of apoptosis. Treatment of ABC294649, an inhibitor of SPHK2, reduced the caspase 3 activity, suggesting the involvement of its kinase activity in apoptosis. Knockdown of SPHK2 significantly reduced caspase 3 activity not only in DENV-infected Huh7 cells but also in DENV-infected HepG2 cells. Our results were consistent across all of the four serotypes of DENV infection, which supports the pro-apoptotic role of SPHK2 in DENV-infected liver cells.

  2. Ultra-deep sequencing reveals high prevalence and broad structural diversity of hepatitis B surface antigen mutations in a global population.

    Science.gov (United States)

    Gencay, Mikael; Hübner, Kirsten; Gohl, Peter; Seffner, Anja; Weizenegger, Michael; Neofytos, Dionysios; Batrla, Richard; Woeste, Andreas; Kim, Hyon-Suk; Westergaard, Gaston; Reinsch, Christine; Brill, Eva; Thu Thuy, Pham Thi; Hoang, Bui Huu; Sonderup, Mark; Spearman, C Wendy; Pabinger, Stephan; Gautier, Jérémie; Brancaccio, Giuseppina; Fasano, Massimo; Santantonio, Teresa; Gaeta, Giovanni B; Nauck, Markus; Kaminski, Wolfgang E

    2017-01-01

    The diversity of the hepatitis B surface antigen (HBsAg) has a significant impact on the performance of diagnostic screening tests and the clinical outcome of hepatitis B infection. Neutralizing or diagnostic antibodies against the HBsAg are directed towards its highly conserved major hydrophilic region (MHR), in particular towards its "a" determinant subdomain. Here, we explored, on a global scale, the genetic diversity of the HBsAg MHR in a large, multi-ethnic cohort of randomly selected subjects with HBV infection from four continents. A total of 1553 HBsAg positive blood samples of subjects originating from 20 different countries across Africa, America, Asia and central Europe were characterized for amino acid variation in the MHR. Using highly sensitive ultra-deep sequencing, we found 72.8% of the successfully sequenced subjects (n = 1391) demonstrated amino acid sequence variation in the HBsAg MHR. This indicates that the global variation frequency in the HBsAg MHR is threefold higher than previously reported. The majority of the amino acid mutations were found in the HBV genotypes B (28.9%) and C (25.4%). Collectively, we identified 345 distinct amino acid mutations in the MHR. Among these, we report 62 previously unknown mutations, which extends the worldwide pool of currently known HBsAg MHR mutations by 22%. Importantly, topological analysis identified the "a" determinant upstream flanking region as the structurally most diverse subdomain of the HBsAg MHR. The highest prevalence of "a" determinant region mutations was observed in subjects from Asia, followed by the African, American and European cohorts, respectively. Finally, we found that more than half (59.3%) of all HBV subjects investigated carried multiple MHR mutations. Together, this worldwide ultra-deep sequencing based genotyping study reveals that the global prevalence and structural complexity of variation in the hepatitis B surface antigen have, to date, been significantly underappreciated.

  3. Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile.

    LENUS (Irish Health Repository)

    Moreau, Isabelle

    2012-02-03

    BACKGROUND: Hepatitis C virus (HCV) circulates in an infected individual as a heterogeneous mixture of closely related viruses called quasispecies. The E1\\/E2 region of the HCV genome is hypervariable (HVR1) and is targeted by the humoral immune system. Hepatitis C virions are found in two forms: antibody associated or antibody free. The objective of this study was to investigate if separation of Hepatitis C virions into antibody enriched and antibody depleted fractions segregates quasispecies populations into distinctive swarms. RESULTS: A HCV genotype 4a specimen was fractionated into IgG-depleted and IgG-enriched fractions by use of Albumin\\/IgG depletion spin column. Clonal analysis of these two fractions was performed and then compared to an unfractionated sample. Following sequence analysis it was evident that the antibody depleted fraction was significantly more heterogeneous than the antibody enriched fraction, revealing a unique quasispecies profile. An in-frame 3 nt insertion was observed in 26% of clones in the unfractionated population and in 64% of clones in the IgG-depleted fraction. In addition, an in-frame 3 nt indel event was observed in 10% of clones in the unfractionated population and in 9% of clones in the IgG-depleted fraction. Neither of these latter events, which are rare occurrences in genotype 4a, was identified in the IgG-enriched fraction. CONCLUSION: In conclusion, the homogeneity of the IgG-enriched species is postulated to represent a sequence that was strongly recognised by the humoral immune system at the time the sample was obtained. The heterogeneous nature of the IgG-depleted fraction is discussed in the context of humoral escape.

  4. Differential regulation of hepatic transcription factors in the Wistar rat offspring born to dams fed folic acid, vitamin B12 deficient diets and supplemented with omega-3 fatty acids.

    Directory of Open Access Journals (Sweden)

    Akshaya Meher

    Full Text Available Nutritional status of the mother is known to influence various metabolic adaptations required for optimal fetal development. These may be mediated by transcription factors like peroxisome proliferator activated receptors (PPARs, which are activated by long chain polyunsaturated fatty acids. The objective of the current study was to examine the expression of different hepatic transcription factors and the levels of global methylation in the liver of the offspring born to dams fed micronutrient deficient (folic acid and vitamin B12 diets and supplemented with omega-3 fatty acids. Female rats were divided into five groups (n = 8/group as follows; control, folic acid deficient (FD, vitamin B12 deficient (BD and omega-3 fatty acid supplemented groups (FDO and BDO. Diets were given starting from pre-conception and continued throughout pregnancy and lactation. Pups were dissected at the end of lactation. Liver tissues were removed; snap frozen and stored at -80°C. Maternal micronutrients deficiency resulted in lower (p<0.05 levels of pup liver docosahexaenoic acid (DHA and arachidonic acid (ARA as compared to the control group. Pup liver PPARα and PPARγ expression was lower (p<0.05 in the BD group although there were no differences in the expression of SREBP-1c, LXRα and RXRα expression. Omega-3 fatty acids supplementation to this group normalized (p<0.05 levels of both PPARα and PPARγ but reduced (p<0.05 SREBP-1c, LXRα and RXRα expression. There was no change in any of the transcription factors in the pup liver in the FD group. Omega-3 fatty acids supplementation to this group reduced (p<0.05 PPARα, SREBP-1c and RXRα expression. Pup liver global methylation levels were higher (p<0.01 in both the micronutrients deficient groups and could be normalized (p<0.05 by omega-3 fatty acid supplementation. Our novel findings suggest a role for omega-3 fatty acids in the one carbon cycle in influencing the hepatic expression of transcription factors

  5. Storage Pool Deficiencies

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  6. A Diverse Panel of Hepatitis C Virus Glycoproteins for Use in Vaccine Research Reveals Extremes of Monoclonal Antibody Neutralization Resistance.

    Science.gov (United States)

    Urbanowicz, Richard A; McClure, C Patrick; Brown, Richard J P; Tsoleridis, Theocharis; Persson, Mats A A; Krey, Thomas; Irving, William L; Ball, Jonathan K; Tarr, Alexander W

    2015-12-23

    Despite significant advances in the treatment of hepatitis C virus (HCV) infection, the need to develop preventative vaccines remains. Identification of the best vaccine candidates and evaluation of their performance in preclinical and clinical development will require appropriate neutralization assays utilizing diverse HCV isolates. We aimed to generate and characterize a panel of HCV E1E2 glycoproteins suitable for subsequent use in vaccine and therapeutic antibody testing. Full-length E1E2 clones were PCR amplified from patient-derived serum samples, cloned into an expression vector, and used to generate viral pseudoparticles (HCVpp). In addition, some of these clones were used to generate cell culture infectious (HCVcc) clones. The infectivity and neutralization sensitivity of these viruses were then determined. Bioinformatic and HCVpp infectivity screening of approximately 900 E1E2 clones resulted in the assembly of a panel of 78 functional E1E2 proteins representing distinct HCV genotypes and different stages of infection. These HCV glycoproteins differed markedly in their sensitivity to neutralizing antibodies. We used this panel to predict antibody efficacy against circulating HCV strains, highlighting the likely reason why some monoclonal antibodies failed in previous clinical trials. This study provides the first objective categorization of cross-genotype patient-derived HCV E1E2 clones according to their sensitivity to antibody neutralization. It has shown that HCV isolates have clearly distinguishable neutralization-sensitive, -resistant, or -intermediate phenotypes, which are independent of genotype. The panel provides a systematic means for characterization of the neutralizing response elicited by candidate vaccines and for defining the therapeutic potential of monoclonal antibodies. Hepatitis C virus (HCV) has a global burden of more than 170 million people, many of whom cannot attain the new, expensive, direct-acting antiviral therapies. A safe and

  7. iRhom2 deficiency relieves TNF-α associated hepatic dyslipidemia in long-term PM2.5-exposed mice.

    Science.gov (United States)

    Ge, Chen-Xu; Qin, Yu-Ting; Lou, De-Shuai; Li, Qiang; Li, Yuan-Yuan; Wang, Zhong-Ming; Yang, Wei-Wei; Wang, Ming; Liu, Nan; Wang, Zhen; Zhang, Peng-Xing; Tu, Yan-Yang; Tan, Jun; Xu, Min-Xuan

    2017-12-02

    Accumulating researches reported that particulate matter (PM2.5) is a risk factor for developing various diseases, including metabolic syndrome. Recently, inactive rhomboid protein 2 (iRhom2) was considered as a necessary modulator for shedding of tumor necrosis factor-α (TNF-α) in immune cells. TNF-α, a major pro-inflammatory cytokine, was linked to various pathogenesis of diseases, including dyslipidemia. Here, wild type (WT) and iRhom2-knockout (iRhom2 -/- ) mice were used to investigate the effects of iRhom2 on PM2.5-induced hepatic dyslipidemia. The hepatic histology, inflammatory response, glucose tolerance, serum parameters and gene expressions were analyzed. We found that long-term inhalation of PM2.5 resulted in hepatic steatosis. And a significant up-regulation of iRhom2 in liver tissues was observed, accompanied with elevated TNF-α, TNF-α converting enzyme (TACE), TNFα receptor (TNFR)2 and various inflammatory cytokines expressions. Additionally, PM2.5 treatment caused TG and TC accumulation in serum and liver, probably attributed to changes of genes modulating lipid metabolism. Intriguingly, hepatic injury and dyslipidemia were attenuated by iRhom2 -/- in mice with PM2.5 challenge. In vitro, iRhom2-knockdwon reduced TNF-α expressions and its associated inflammatory cytokines in Kupffer cells, implying that liver-resident macrophages played an important role in regulating hepatic inflammation and lipid metabolism in cells treated with PM2.5. The findings indicated that long-term PM2.5 exposure caused hepatic steatosis and dyslipidemia through triggering inflammation, which was, at least partly, dependent on iRhom2/TNF-α pathway in liver-resident macrophages. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. 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. Copyright © 2014 Wiley Periodicals, Inc.

  9. Autoimmune hepatitis.

    Science.gov (United States)

    Vergani, D; Mieli-Vergani, G

    2004-06-01

    Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.

  10. A novel mouse model reveals that polycystin-1 deficiency in ependyma and choroid plexus results in dysfunctional cilia and hydrocephalus.

    Directory of Open Access Journals (Sweden)

    Claas Wodarczyk

    2009-09-01

    Full Text Available Polycystin-1 (PC-1, the product of the PKD1 gene, mutated in the majority of cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD, is a very large (approximately 520 kDa plasma membrane receptor localized in several subcellular compartments including cell-cell/matrix junctions as well as cilia. While heterologous over-expression systems have allowed identification of several of the potential biological roles of this receptor, its precise function remains largely elusive. Studying PC-1 in vivo has been a challenging task due to its complexity and low expression levels. To overcome these limitations and facilitate the study of endogenous PC-1, we have inserted HA- or Myc-tag sequences into the Pkd1 locus by homologous recombination. Here, we show that our approach was successful in generating a fully functional and easily detectable endogenous PC-1. Characterization of PC-1 distribution in vivo showed that it is expressed ubiquitously and is developmentally-regulated in most tissues. Furthermore, our novel tool allowed us to investigate the role of PC-1 in brain, where the protein is abundantly expressed. Subcellular localization of PC-1 revealed strong and specific staining in ciliated ependymal and choroid plexus cells. Consistent with this distribution, we observed hydrocephalus formation both in the ubiquitous knock-out embryos and in newborn mice with conditional inactivation of the Pkd1 gene in the brain. Both choroid plexus and ependymal cilia were morphologically normal in these mice, suggesting a role for PC-1 in ciliary function or signalling in this compartment, rather than in ciliogenesis. We propose that the role of PC-1 in the brain cilia might be to prevent hydrocephalus, a previously unrecognized role for this receptor and one that might have important implications for other genetic or sporadic diseases.

  11. Systematic identification of anti-interferon function on hepatitis C virus genome reveals p7 as an immune evasion protein.

    Science.gov (United States)

    Qi, Hangfei; Chu, Virginia; Wu, Nicholas C; Chen, Zugen; Truong, Shawna; Brar, Gurpreet; Su, Sheng-Yao; Du, Yushen; Arumugaswami, Vaithilingaraja; Olson, C Anders; Chen, Shu-Hua; Lin, Chung-Yen; Wu, Ting-Ting; Sun, Ren

    2017-02-21

    Hepatitis C virus (HCV) encodes mechanisms to evade the multilayered antiviral actions of the host immune system. Great progress has been made in elucidating the strategies HCV employs to down-regulate interferon (IFN) production, impede IFN signaling transduction, and impair IFN-stimulated gene (ISG) expression. However, there is a limited understanding of the mechanisms governing how viral proteins counteract the antiviral functions of downstream IFN effectors due to the lack of an efficient approach to identify such interactions systematically. To study the mechanisms by which HCV antagonizes the IFN responses, we have developed a high-throughput profiling platform that enables mapping of HCV sequences critical for anti-IFN function at high resolution. Genome-wide profiling performed with a 15-nt insertion mutant library of HCV showed that mutations in the p7 region conferred high levels of IFN sensitivity, which could be alleviated by the expression of WT p7 protein. This finding suggests that p7 protein of HCV has an immune evasion function. By screening a liver-specific ISG library, we identified that IFI6-16 significantly inhibits the replication of p7 mutant viruses without affecting WT virus replication. In contrast, knockout of IFI6-16 reversed the IFN hypersensitivity of p7 mutant virus. In addition, p7 was found to be coimmunoprecipitated with IFI6-16 and to counteract the function of IFI6-16 by depolarizing the mitochondria potential. Our data suggest that p7 is a critical immune evasion protein that suppresses the antiviral IFN function by counteracting the function of IFI6-16.

  12. Genogeography and Immune Epitope Characteristics of Hepatitis B Virus Genotype C Reveals Two Distinct Types: Asian and Papua-Pacific.

    Directory of Open Access Journals (Sweden)

    Meta Dewi Thedja

    Full Text Available Distribution of hepatitis B virus (HBV genotypes/subgenotypes is geographically and ethnologically specific. In the Indonesian archipelago, HBV genotype C (HBV/C is prevalent with high genome variability, reflected by the presence of 13 of currently existing 16 subgenotypes. We investigated the association between HBV/C molecular characteristics with host ethnicity and geographical distribution by examining various subgenotypes of HBV/C isolates from the Asia and Pacific region, with further analysis on the immune epitope characteristics of the core and surface proteins. Phylogenetic tree was constructed based on complete HBV/C genome sequences from Asia and Pacific region, and genetic distance between isolates was also examined. HBV/C surface and core immune epitopes were analyzed and grouped by comparing the amino acid residue characteristics and geographical origins. Based on phylogenetic tree and geographical origins of isolates, two major groups of HBV/C isolates--East-Southeast Asia and Papua-Pacific--were identified. Analysis of core and surface immune epitopes supported these findings with several amino acid substitutions distinguishing the East-Southeast Asia isolates from the Papua-Pacific isolates. A west-to-east gradient of HBsAg subtype distribution was observed with adrq+ prominent in the East and Southeast Asia and adrq- in the Pacific, with several adrq-indeterminate subtypes observed in Papua and Papua New Guinea (PNG. This study indicates that HBV/C isolates can be classified into two types, the Asian and the Papua-Pacific, based on the virus genome diversity, immune epitope characteristics, and geographical distribution, with Papua and PNG as the molecular evolutionary admixture region in the switching from adrq+ to adrq-.

  13. Mutational analysis of the hypervariable region of hepatitis e virus reveals its involvement in the efficiency of viral RNA replication.

    Science.gov (United States)

    Pudupakam, R S; Kenney, Scott P; Córdoba, Laura; Huang, Yao-Wei; Dryman, Barbara A; Leroith, Tanya; Pierson, F William; Meng, Xiang-Jin

    2011-10-01

    The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication levels of the HVR deletion mutants were markedly reduced in Huh7 cells, suggesting a role of the HVR in viral replication efficiency. To further verify the results, we constructed HVR deletion mutants by using a genetically divergent, nonmammalian avian HEV, and similar effects on viral replication efficiency were observed when the avian HEV mutants were tested in LMH cells. Furthermore, the impact of complete HVR deletion on virus infectivity was tested in chickens, using an avian HEV mutant with a complete HVR deletion. Although the deletion mutant was still replication competent in LMH cells, the complete HVR deletion resulted in a loss of avian HEV infectivity in chickens. Since the HVR exhibits extensive variations in sequence and length among different HEV genotypes, we further examined the interchangeability of HVRs and demonstrated that HVR sequences are functionally exchangeable between HEV genotypes with regard to viral replication and infectivity in vitro, although genotype-specific HVR differences in replication efficiency were observed. The results showed that although the HVR tolerates small deletions with regard to infectivity, it may interact with viral and host factors to modulate the efficiency of HEV replication.

  14. Adaptation to human populations is revealed by within-host polymorphisms in HIV-1 and hepatitis C virus.

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    Art F Y Poon

    2007-03-01

    Full Text Available CD8(+ cytotoxic T-lymphocytes (CTLs perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1 and hepatitis C virus (HCV. As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately "toggle" in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1- (n > or = 3,000 and HCV-infected patients (n > or = 2,600 by screening bulk RT-PCR sequences for sequencing "mixtures" (i.e., ambiguous nucleotides, which act as site-specific markers of genetic variation within each host. We find that nonsynonymous mixtures are abundant and significantly associated with codon positions under host-specific CTL selection, which should deplete within-host variation by driving the fixation of the favored variant. Using a simple model, we demonstrate that this apparently contradictory outcome can be explained by the transmission of unfavorable variants to new hosts before they are removed by selection, which occurs more frequently when selection and transmission occur on similar time scales. Consequently, the circulating virus population is shaped by the transmission rate and the disparity in selection intensities for escape or reversion as much as it is shaped by the immune diversity of the host population, with potentially serious implications for vaccine design.

  15. Structural analysis of eight novel and 112 previously reported missense mutations in the interactive FXI mutation database reveals new insight on FXI deficiency.

    Science.gov (United States)

    Saunders, Rebecca E; Shiltagh, Nuha; Gomez, Keith; Mellars, Gillian; Cooper, Carolyn; Perry, David J; Tuddenham, Edward G; Perkins, Stephen J

    2009-08-01

    Factor XI (FXI) functions in blood coagulation. FXI is composed of four apple (Ap) domains and a serine protease (SP) domain. Deficiency of FXI leads to an injury-related bleeding disorder, which is remarkable for the lack of correlation between bleeding symptoms and FXI coagulant activity (FXI:C). The number of mutations previously reported in our interactive web database (http://www.FactorXI.org) is now significantly increased to 183 through our new patient studies and from literature surveys. Eight novel missense mutations give a total of 120 throughout the FXI gene (F11). The most abundant defects in FXI are revealed to be those from low-protein plasma levels (Type I: CRM-) that originate from protein misfolding, rather than from functional defects (Type II: CRM+). A total of 70 Ap missense mutations were analysed using a consensus Ap domain structure generated from the FXI dimer crystal structure. This showed that all parts of the Ap domain were affected. The 47 SP missense mutations were also distributed throughout the SP domain structure. The periphery of the Ap beta-sheet structure is sensitive to structural perturbation caused by residue changes throughout the Ap domain, yet this beta-sheet is crucial for FXI dimer formation. Residues located at the Ap4:Ap4 interface in the dimer are much less directly involved. We conclude that the abundance of Type I defects in FXI results from the sensitivity of the Ap domain folding to residue changes within this, and discuss how structural knowledge of the mutations improves our understanding of FXI deficiencies.

  16. Hepatic Encephalopathy

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    Full Text Available ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ...

  17. Viral Hepatitis

    Science.gov (United States)

    ... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

  18. Hepatitis B

    Science.gov (United States)

    ... B Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans ... in their blood (sometimes referred to as the hepatitis B viral load) and an unusually high level of a ...

  19. Molecular footprints reveal the impact of the protective HLA-A*03 allele in hepatitis C virus infection.

    LENUS (Irish Health Repository)

    Fitzmaurice, Karen

    2012-02-01

    BACKGROUND AND AIMS: CD8 T cells are central to the control of hepatitis C virus (HCV) although the key features of a successful CD8 T cell response remain to be defined. In a cohort of Irish women infected by a single source, a strong association between viral clearance and the human lecucocyte (HLA)-A*03 allele has been described, and the aim of this study was to define the protective nature of the associated CD8 T cell response. METHODS: A sequence-led approach was used to identify HLA-A*03-restricted epitopes. We examine the CD8 T cell response associated with this gene and address the likely mechanism underpinning this protective effect in this special cohort, using viral sequencing, T cell assays and analysis of fitness of viral mutants. RESULTS: A strong \\'HLA footprint\\' in a novel NS3 epitope (TVYHGAGTK) was observed. A lysine (K) to arginine (R) substitution at position 9 (K1088R) was seen in a significant number of A*03-positive patients (9\\/12) compared with the control group (1\\/33, p=0.0003). Threonine (T) was also substituted with alanine (A) at position 8 (T1087A) more frequently in A*03-positive patients (6\\/12) compared with controls (2\\/33, p=0.01), and the double substitution of TK to AR was also observed predominantly in HLA-A*03-positive patients (p=0.004). Epitope-specific CD8 T cell responses were observed in 60% of patients three decades after exposure and the mutants selected in vivo impacted on recognition in vitro. Using HCV replicons matched to the viral sequences, viral fitness was found to be markedly reduced by the K1088R substitution but restored by the second substitution T1087A. CONCLUSIONS: It is proposed that at least part of the protective effect of HLA-A*03 results from targeting of this key epitope in a functional site: the requirement for two mutations to balance fitness and escape provides an initial host advantage. This study highlights the potential protective impact of common HLA-A alleles against persistent

  20. Gender affects skin wound healing in plasminogen deficient mice.

    Directory of Open Access Journals (Sweden)

    Birgitte Rønø

    Full Text Available The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin

  1. Carnitine Deficiency and Pregnancy

    Directory of Open Access Journals (Sweden)

    Anouk de Bruyn

    2015-01-01

    Full Text Available We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, supplementation with carnitine is advised. This supplementation should be continued throughout pregnancy according to plasma concentrations.

  2. Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats

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    Aaron A. Mehus

    2017-10-01

    Full Text Available Metallothioneins (MTs perform important regulatory and cytoprotective functions in tissues including the brain. While it is known that energy restriction (ER and dietary n-3 polyunsaturated fatty acid (PUFA deficiency impact postnatal brain growth and development, little data exist regarding the impact of undernutrition upon MT expression in growing animals. We tested the hypothesis that ER with and without dietary n-3 PUFA deficiency reduces MT expression in juvenile rats. ER rats were individually pair-fed at 75% of the ad libitum (AL intake of control rats provided diets consisting of either soybean oil (SO that is α-linolenic acid (ALA; 18:3n-3 sufficient or corn oil (CO; ALA-deficient. Fatty acids (FA and metal concentrations of liver and brain regions were analyzed. Tissue expression of MTs (Mt1-3 and modulators of MT expression including glucocorticoid receptors (Nr3c1 and Nr3c2 and several mediators of thyroid hormone regulation (Dio1-3, Mct8, Oatp1c1, Thra, and Thrb were measured. Plasma corticosterone and triiodothyronine levels were also evaluated. ER, but not metal deficiency, reduced Mt2 expression in the cerebellum (50% and cerebral cortex (23%. In liver, a reduction in dietary n-3 PUFA reduced Mt1, Mt2, Nr3c1, Mct8, and Thrb. ER elevated Nr3c1, Dio1, and Thrb and reduced Thra in the liver. Given MT’s role in cellular protection, further studies are needed to evaluate whether ER or n-3 PUFA deficiency may leave the juvenile brain and/or liver more susceptible to endogenous or environmental stressors.

  3. Single-cell transcriptomic reconstruction reveals cell cycle and multi-lineage differentiation defects in Bcl11a-deficient hematopoietic stem cells.

    Science.gov (United States)

    Tsang, Jason C H; Yu, Yong; Burke, Shannon; Buettner, Florian; Wang, Cui; Kolodziejczyk, Aleksandra A; Teichmann, Sarah A; Lu, Liming; Liu, Pentao

    2015-09-21

    Hematopoietic stem cells (HSCs) are a rare cell type with the ability of long-term self-renewal and multipotency to reconstitute all blood lineages. HSCs are typically purified from the bone marrow using cell surface markers. Recent studies have identified significant cellular heterogeneities in the HSC compartment with subsets of HSCs displaying lineage bias. We previously discovered that the transcription factor Bcl11a has critical functions in the lymphoid development of the HSC compartment. In this report, we employ single-cell transcriptomic analysis to dissect the molecular heterogeneities in HSCs. We profile the transcriptomes of 180 highly purified HSCs (Bcl11a (+/+) and Bcl11a (-/-)). Detailed analysis of the RNA-seq data identifies cell cycle activity as the major source of transcriptomic variation in the HSC compartment, which allows reconstruction of HSC cell cycle progression in silico. Single-cell RNA-seq profiling of Bcl11a (-/-) HSCs reveals abnormal proliferative phenotypes. Analysis of lineage gene expression suggests that the Bcl11a (-/-) HSCs are constituted of two distinct myeloerythroid-restricted subpopulations. Remarkably, similar myeloid-restricted cells could also be detected in the wild-type HSC compartment, suggesting selective elimination of lymphoid-competent HSCs after Bcl11a deletion. These defects are experimentally validated in serial transplantation experiments where Bcl11a (-/-) HSCs are myeloerythroid-restricted and defective in self-renewal. Our study demonstrates the power of single-cell transcriptomics in dissecting cellular process and lineage heterogeneities in stem cell compartments, and further reveals the molecular and cellular defects in the Bcl11a-deficient HSC compartment.

  4. Dexmedetomidine (DEX) protects against hepatic ischemia/reperfusion (I/R) injury by suppressing inflammation and oxidative stress in NLRC5 deficient mice.

    Science.gov (United States)

    Chen, Zong; Ding, Tao; Ma, Chuan-Gen

    2017-11-18

    Hepatic ischemia/reperfusion (I/R) injury could arise as a complication of liver surgery and transplantation. No specific therapeutic strategies are available to attenuate I/R injury. NOD-, LRR-and CARD-containing 5 (NLRC5), a member of the NOD-like protein family, has been suggested to negatively regulate nuclear factor kappa B (NF-κB) through interacting with IKKα and blocking their phosphorylation. Dexmedetomidine (DEX) has been shown to attenuate liver injury. In the current study, we investigated the pre-treatment of DEX on hepatic I/R injury in wild type (WT) and NLRC5 knockout (NLRC5 -/- ) mice. Our results indicated that NLRC5 -/- showed significantly stronger histologic damage, inflammatory response, oxidative stress and apoptosis after I/R compared to the WT group of mice, indicating the protective role of NLRC5 against liver I/R injury. Importantly, I/R-induced increase of NLRC5 was reduced by DEX pre-treatment. After hepatic I/R injury, WT and NLRC5 -/- mice pre-treated with DEX exhibited attenuated histological disruption, and reduced pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and inducible nitric oxide synthase (iNOS), which was associated with the inactivated NF-κB pathway. Moreover, suppression of oxidative stress and apoptosis was observed in DEX-treated mice with I/R injury, probably through enhancing nuclear factor erythroid 2-related factor 2 (Nrf2), reducing mitogen-activated protein kinases (MAPKs) and Caspase-3/poly (ADP-ribose) polymerase (PARP) pathways. In vitro, the results were further confirmed in WT and NLRC5 -/- hepatocytes pre-treated with or without DEX. Together, the findings illustrated that lack of NLRC5 resulted in severer liver I/R injury, which could be alleviated by DEX pre-treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Effects of Fe and Mn deficiencies on the protein profiles of tomato (Solanum lycopersicum) xylem sap as revealed by shotgun analyses.

    Science.gov (United States)

    Ceballos-Laita, Laura; Gutierrez-Carbonell, Elain; Takahashi, Daisuke; Abadía, Anunciación; Uemura, Matsuo; Abadía, Javier; López-Millán, Ana Flor

    2018-01-06

    The aim of this work was to study the effects of Fe and Mn deficiencies on the xylem sap proteome of tomato using a shotgun proteomic approach, with the final goal of elucidating plant response mechanisms to these stresses. This approach yielded 643 proteins reliably identified and quantified with 70% of them predicted as secretory. Iron and Mn deficiencies caused statistically significant and biologically relevant abundance changes in 119 and 118 xylem sap proteins, respectively. In both deficiencies, metabolic pathways most affected were protein metabolism, stress/oxidoreductases and cell wall modifications. First, results suggest that Fe deficiency elicited more stress responses than Mn deficiency, based on the changes in oxidative and proteolytic enzymes. Second, both nutrient deficiencies affect the secondary cell wall metabolism, with changes in Fe deficiency occurring via peroxidase activity, and in Mn deficiency involving peroxidase, Cu-oxidase and fasciclin-like arabinogalactan proteins. Third, the primary cell wall metabolism was affected by both nutrient deficiencies, with changes following opposite directions as judged from the abundances of several glycoside-hydrolases with endo-glycolytic activities and pectin esterases. Fourth, signaling pathways via xylem involving CLE and/or lipids as well as changes in phosphorylation and N-glycosylation also play a role in the responses to these stresses. Biological significance In spite of being essential for the delivery of nutrients to the shoots, our knowledge of xylem responses to nutrient deficiencies is very limited. The present work applies a shotgun proteomic approach to unravel the effects of Fe and Mn deficiencies on the xylem sap proteome. Overall, Fe deficiency seems to elicit more stress in the xylem sap proteome than Mn deficiency, based on the changes measured in proteolytic and oxido-reductase proteins, whereas both nutrients exert modifications in the composition of the primary and secondary

  6. Sensitive luminescent reporter viruses reveal appreciable release of hepatitis C virus NS5A protein into the extracellular environment.

    Science.gov (United States)

    Eyre, Nicholas S; Aloia, Amanda L; Joyce, Michael A; Chulanetra, Monrat; Tyrrell, D Lorne; Beard, Michael R

    2017-07-01

    The HCV NS5A protein is essential for viral RNA replication and virus particle assembly. To study the viral replication cycle and NS5A biology we generated an infectious HCV construct with a NanoLuciferase (NLuc) insertion within NS5A. Surprisingly, beyond its utility as a sensitive reporter of cytoplasmic viral RNA replication, we also observed strong luminescence in cell culture fluids. Further analysis using assembly-defective viruses and subgenomic replicons revealed that infectious virus production was not required for extracellular NS5A-NLuc activity but was associated with enrichment of extracellular NS5A-NLuc in intermediate-density fractions similar to those of exosomes and virus particles. Additionally, BRET analysis indicated that intracellular and extracellular forms of NS5A may adopt differing conformations. Importantly, infection studies using a human liver chimeric mouse model confirmed robust infection in vivo and ready detection of NLuc activity in serum. We hypothesise that the presence of NS5A in extracellular fluids contributes to HCV pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. AUTOIMMUNE HEPATITIS

    Directory of Open Access Journals (Sweden)

    Yusri Dianne Jurnalis

    2010-05-01

    ; Aetiopathogenesis; Lymphocyte disease; Cellular immune attack; Histocompatibility lymphocyte antigen, Immunosuppressive therapy, Cyclosporine, transplantasi hatiAbstractAutoimmune hepatitis is a severe and inflammatory disease of the liver of unknown etiology carrying high morbidity and mortality. All ages and genders are concerned with a peak of incidence in girls in prepubertal age, even if the diseaseTINJAUAN PUSTAKA2has been diagnosed as early as 6 months. Autoimmune hepatitis may be classified in two major subgroups on a presence of a specific set of autoantibodies: smooth muscle antibody (SMA mostly with anti-actin specificity and/or by antinuclear antibody (ANA in type 1 and liver-kidney microsome antibody (LKM1 and/or the anti-liver cytosol in type 2. The histological hallmark is “interface hepatitis”, with a mononuclear cell infiltrate in the portal tracts, variable degrees of necrosis, and progressive fibrosis. The disease follows a chronic but fluctuating course usually progressing to cirrhosis and liver failure.The most frequent type onset is similar to that of an acute viral hepatitis with acute liver failure in some patients; about a third of patients have an insidious onset with progressive fatigue and jaundice while 10-15% are asymptomatic and are accidentally discovered by the finding of hepatomegaly and/or an increase of serum aminotransferase activity. There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups.Corticosteroids alone or in conjunction with azathioprine are the treatment of choice inducing remission in over 90% of patients. An alternative therapeutic strategy is cyclosporine. Withdrawal of immunosuppression is associated with high risk

  8. Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo.

    Science.gov (United States)

    Jurkowska, Halina; Niewiadomski, Julie; Hirschberger, Lawrence L; Roman, Heather B; Mazor, Kevin M; Liu, Xiaojing; Locasale, Jason W; Park, Eunkyue; Stipanuk, Martha H

    2016-03-01

    The cysteine dioxygenase (Cdo1)-null and the cysteine sulfinic acid decarboxylase (Csad)-null mouse are not able to synthesize hypotaurine/taurine by the cysteine/cysteine sulfinate pathway and have very low tissue taurine levels. These mice provide excellent models for studying the effects of taurine on biological processes. Using these mouse models, we identified betaine:homocysteine methyltransferase (BHMT) as a protein whose in vivo expression is robustly regulated by taurine. BHMT levels are low in liver of both Cdo1-null and Csad-null mice, but are restored to wild-type levels by dietary taurine supplementation. A lack of BHMT activity was indicated by an increase in the hepatic betaine level. In contrast to observations in liver of Cdo1-null and Csad-null mice, BHMT was not affected by taurine supplementation of primary hepatocytes from these mice. Likewise, CSAD abundance was not affected by taurine supplementation of primary hepatocytes, although it was robustly upregulated in liver of Cdo1-null and Csad-null mice and lowered to wild-type levels by dietary taurine supplementation. The mechanism by which taurine status affects hepatic CSAD and BHMT expression appears to be complex and to require factors outside of hepatocytes. Within the liver, mRNA abundance for both CSAD and BHMT was upregulated in parallel with protein levels, indicating regulation of BHMT and CSAD mRNA synthesis or degradation.

  9. Hepatitis B virus X protein (HBx)-induced abnormalities of nucleic acid metabolism revealed by (1)H-NMR-based metabonomics.

    Science.gov (United States)

    Dan Yue; Zhang, Yuwei; Cheng, Liuliu; Ma, Jinhu; Xi, Yufeng; Yang, Liping; Su, Chao; Shao, Bin; Huang, Anliang; Xiang, Rong; Cheng, Ping

    2016-04-14

    Hepatitis B virus X protein (HBx) plays an important role in HBV-related hepatocarcinogenesis; however, mechanisms underlying HBx-mediated carcinogenesis remain unclear. In this study, an NMR-based metabolomics approach was applied to systematically investigate the effects of HBx on cell metabolism. EdU incorporation assay was conducted to examine the effects of HBx on DNA synthesis, an important feature of nucleic acid metabolism. The results revealed that HBx disrupted metabolism of glucose, lipids, and amino acids, especially nucleic acids. To understand the potential mechanism of HBx-induced abnormalities of nucleic acid metabolism, gene expression profiles of HepG2 cells expressing HBx were investigated. The results showed that 29 genes involved in DNA damage and DNA repair were differentially expressed in HBx-expressing HepG2 cells. HBx-induced DNA damage was further demonstrated by karyotyping, comet assay, Western blotting, immunofluorescence and immunohistochemistry analyses. Many studies have previously reported that DNA damage can induce abnormalities of nucleic acid metabolism. Thus, our results implied that HBx initially induces DNA damage, and then disrupts nucleic acid metabolism, which in turn blocks DNA repair and induces the occurrence of hepatocellular carcinoma (HCC). These findings further contribute to our understanding of the occurrence of HCC.

  10. Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Takashi Himoto

    2018-01-01

    Full Text Available Zinc (Zn is an essential trace element which has favorable antioxidant, anti-inflammatory, and apoptotic effects. The liver mainly plays a crucial role in maintaining systemic Zn homeostasis. Therefore, the occurrence of chronic liver diseases, such as chronic hepatitis, liver cirrhosis, or fatty liver, results in the impairment of Zn metabolism, and subsequently Zn deficiency. Zn deficiency causes plenty of metabolic abnormalities, including insulin resistance, hepatic steatosis and hepatic encephalopathy. Inversely, metabolic abnormalities like hypoalbuminemia in patients with liver cirrhosis often result in Zn deficiency. Recent studies have revealed the putative mechanisms by which Zn deficiency evokes a variety of metabolic abnormalities in chronic liver disease. Zn supplementation has shown beneficial effects on such metabolic abnormalities in experimental models and actual patients with chronic liver disease. This review summarizes the pathogenesis of metabolic abnormalities deriving from Zn deficiency and the favorable effects of Zn administration in patients with chronic liver disease. In addition, we also highlight the interactions between Zn and other trace elements, vitamins, amino acids, or hormones in such patients.

  11. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice ... diseases. What are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty ...

  12. Dietary genistein supplementation in laying broiler breeder hens alters the development and metabolism of offspring embryos as revealed by hepatic transcriptome analysis.

    Science.gov (United States)

    Lv, Zengpeng; Fan, Hao; Zhang, Beibei; Ning, Chao; Xing, Kun; Guo, Yuming

    2018-03-08

    capacity, as a result of maternal GEN effects, was conducive to embryonic development. In conclusion, the addition of GEN to the diet of laying broiler breeder hens significantly promoted the development and metabolism of chick embryos.-Lv, Z., Fan, H., Zhang, B., Ning, C., Xing, K., Guo, Y. Dietary genistein supplementation in laying broiler breeder hens alters the development and metabolism of offspring embryos as revealed by hepatic transcriptome analysis.

  13. Serological and virological survey of hepatitis E virus (HEV) in animal reservoirs from Uruguay reveals elevated prevalences and a very close phylogenetic relationship between swine and human strains.

    Science.gov (United States)

    Mirazo, Santiago; Gardinali, Noemí R; Cecilia, D'Albora; Verger, Lorenzo; Ottonelli, Florencia; Ramos, Natalia; Castro, Gustavo; Pinto, Marcelo A; Ré, Viviana; Pisano, Belén; Lozano, Alejandra; de Oliveira, Jaqueline Mendes; Arbiza, Juan

    2018-01-01

    Hepatitis E virus (HEV) infection is an issue of public health concern in high-income and non-endemic countries. Increasing evidence supports the hypothesis of a zoonotic route as the main mode of infection in this epidemiological setting, since the transmission of genotypes HEV-3 and HEV-4 from reservoirs to humans has been demonstrated. In America, studies have confirmed the circulation of HEV in pig herds but the zoonotic role of wild boars has never been evaluated. Uruguay has a high burden of HEV- associated acute hepatitis, and a close phylogenetic relationship was observed among human HEV-3 strains and European isolates detected in swine. However in this context, swine herds have never been surveyed. Herein is reported a survey of HEV in swine herds, pigs at slaughter-house and free-living wild boar populations. Two-hundred and twenty sera and 150 liver tissue samples from domestic pigs, and 140 sera from wild boars were tested for HEV by ELISA and PCR-based approaches. All tested swine farms resulted seropositive with an overall rate of 46.8%. In turn, 22.1% of the wild boars had anti-HEV antibodies. HEV RNA was detected in 16.6% and 9.3% of liver samples from slaughter-age pigs and adult wild boars sera, respectively. Three strains from domestic pig were also amplified by nested-PCR approaches. By contrast, none of the positive samples obtained from wild boars could be confirmed by nested-PCR. Phylogenetic analysis revealed a very high nucleotide identity among swine strains and sequences obtained from humans in Uruguay. Results showed that HEV is widely distributed among swine herds in Uruguay. Additionally, this study evidences for the first time in the American continent that wild boar populations are a reservoir for HEV, though its zoonotic role remains to be elucidated. Altogether, data presented here suggest a high zoonotic risk of HEV transmission from swine to humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Adaptations of hepatic amino acid uptake and net utilisation contributes to nitrogen economy or waste in lambs fed nitrogen- or energy-deficient diets.

    Science.gov (United States)

    Kraft, G; Ortigues-Marty, I; Durand, D; Rémond, D; Jardé, T; Bequette, B; Savary-Auzeloux, I

    2011-04-01

    We investigated the effect of relative changes in dietary nitrogen (N) and energy supply and the subsequent variations in net portal appearance (NPA) of nitrogenous and energy nutrients on the net amino acid (AA) uptake by the liver and net N supply to the peripheral tissues. Six lambs were catheterised across the splanchnic tissues and received, in a replicated Latin square, one of three dietary treatments. The diets were formulated to either match the requirements of N and energy (C), or supply only 0.8 of the N requirement (LN) or 0.8 of the energy requirement (LE). Net fluxes of AA and urea-N were measured across the portal-drained viscera, and estimation of arterial hepatic flow allowed the estimation of hepatic fluxes. Catheters were implanted into the portal and hepatic veins as well as in the abdominal aorta for the measurement of AA fluxes. Animals fed the LN diet showed more efficient N retention (0.59 of digested N) than did the C and LE diet (0.50 and 0.33, respectively; P < 0.001). The NPA of total AA-N for the LN diet was only 0.60 of the value measured for the control (C) diet (P < 0.01). Despite this, the total estimated AA-N net splanchnic fluxes were not significantly different across the three diets (3.3, 1.9 and 2.6 g total AA-N/day for C, LN and LE, respectively, P = 0.52). Thus, different metabolic regulations must have taken place across the liver between the three experimental diets. A combination of decreased net uptake of total AA-N by the liver of animals in the LN diet (0.61 of the C diet; P = 0.002) and reduced urinary urea-N production (0.52 of the C diet; P = 0.001) spared AA from catabolism in the LN diet relative to the other two diets. For the LE diet, the urinary urea-N output was 1.3 times the value of the C diet (P = 0.01). This may relate to an increased catabolism of AA by the muscle and/or, to a lesser extent, to an increased utilisation of AA for gluconeogenesis in the liver. These effects may explain the reduced whole body

  15. A novel motion analysis approach reveals late recovery in C57BL/6 mice and deficits in NCAM-deficient mice after sciatic nerve crush.

    Science.gov (United States)

    Fey, Andreas; Schachner, Melitta; Irintchev, Andrey

    2010-05-01

    Assessment of motor abilities after sciatic nerve injury in rodents, in particular mice, relies exclusively on walking track (footprint) analysis despite known limitations of this method. Using principles employed recently for video-based motion analyses after femoral nerve and spinal cord injuries, we have designed and report here a novel approach for functional assessments after sciatic nerve lesions in mice. Functional deficits are estimated by angle and distance measurements on single video frames recorded during beam-walking and inclined ladder climbing. Analyses of adult C57BL/6J mice after crush of the sciatic, tibial, or peroneal nerve allowed the identification of six numerical parameters, detecting impairments of the plantar flexion of the foot and the toe spread. Some of these parameters, as well as footprint functional indices, revealed severe impairment after crush injury of the sciatic or tibial, but not the peroneal nerve, and complete recovery within 3 weeks after lesion. Other novel estimates, however, showed that complete recovery is reached as late as 2-3 months after sciatic nerve crush. These measures detected both tibial and peroneal dysfunction. In contrast to the complete restoration of function in wild-type mice (100%), our new parameters, in contrast to the sciatic functional index, showed incomplete recovery (85%) 90 days after sciatic nerve crush in mice deficient in the neural cell adhesion molecule (NCAM). We conclude that the novel video-based approach is more precise, sensitive, and versatile than established tests, allowing objective numerical assessment of different motor functions in a sciatic nerve injury paradigm in mice.

  16. Overlapping but distinct specificities of anti-liver-kidney microsome antibodies in autoimmune hepatitis type II and hepatitis C revealed by recombinant native CYP2D6 and novel peptide epitopes

    Science.gov (United States)

    Klein, R; Zanger, U M; Berg, T; Hopf, U; Berg, P A

    1999-01-01

    Anti-liver-kidney microsome antibodies (anti-LKM) occur in autoimmune hepatitis (AIH) type II and in a subset of patients with hepatitis C. Anti-LKM1 in AIH are directed against cytochrome P4502D6 (CYP2D6), but conflicting data exist concerning the specificity of anti-LKM in hepatitis C. The aim of this study was to evaluate binding specificities of anti-LKM antibodies in both diseases using novel test antigens as well as their inhibitory capacity on CYP2D6 enzyme activity. Sera from 22 patients with AIH type II and 17 patients with hepatitis C being anti-LKM-positive in the immunofluorescence test were investigated for binding to native recombinant CYP2D6 and liver microsomes by ELISA and immunoblotting, and to synthetic peptides covering the region 254–339 (254–273, 257–269, 270–294, 291–310, 307–324, 321–339, 373–389) as well as the novel peptide 196–218 by ELISA. Furthermore, all sera were tested for inhibition of CYP2D6-dependent bufuralol 1′-hydroxylase activity. Twenty of the 22 AIH type II sera (91%) and nine of the 17 hepatitis C sera (53%) were positive for CYP2D6 by ELISA and/or immunoblotting. The previously described major peptide epitope comprising CYP2D6 amino acids 257–269 was recognized by 16 of the 22 AIH sera but by only one hepatitis C serum. A further epitope, 196–218, could be defined for the first time as another immunodominant epitope for AIH because it was recognized by 15 of the 22 AIH (68%) but only three of the 17 hepatitis C sera (18%). With the exception of the peptide 254–273, the other peptides showed no significant reactivity. Analysing the inhibitory properties of anti-LKM antibodies it emerged that 95% of AIH sera and 88% of hepatitis C sera inhibited enzyme function. These data indicate that anti-LKM antibodies in AIH and hepatitis C react with CYP2D6, as shown by their inhibitory activity, and that besides the known epitope 257–269 a further immunodominant epitope exists on CYP2D6 which is recognized

  17. Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver.

    Science.gov (United States)

    Hinrichs, Arne; Kessler, Barbara; Kurome, Mayuko; Blutke, Andreas; Kemter, Elisabeth; Bernau, Maren; Scholz, Armin M; Rathkolb, Birgit; Renner, Simone; Bultmann, Sebastian; Leonhardt, Heinrich; de Angelis, Martin Hrabĕ; Nagashima, Hiroshi; Hoeflich, Andreas; Blum, Werner F; Bidlingmaier, Martin; Wanke, Rüdiger; Dahlhoff, Maik; Wolf, Eckhard

    2018-05-01

    Laron syndrome (LS) is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR) gene. To establish a large animal model for LS, pigs with GHR knockout (KO) mutations were generated and characterized. CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs. Since the latter two groups were not significantly different in any parameter investigated, they were pooled as the GHR expressing control group. The characterization program included body and organ growth, body composition, endocrine and clinical-chemical parameters, as well as signaling studies in liver tissue. GHR-KO pigs lacked GHR and had markedly reduced serum insulin-like growth factor 1 (IGF1) levels and reduced IGF-binding protein 3 (IGFBP3) activity but increased IGFBP2 levels. Serum GH concentrations were significantly elevated compared with control pigs. GHR-KO pigs had a normal birth weight. Growth retardation became significant at the age of five weeks. At the age of six months, the body weight of GHR-KO pigs was reduced by 60% compared with controls. Most organ weights of GHR-KO pigs were reduced proportionally to body weight. However, the weights of liver, kidneys, and heart were disproportionately reduced, while the relative brain weight was almost doubled. GHR-KO pigs had a markedly increased percentage of total body fat relative to body weight and displayed transient juvenile hypoglycemia along with decreased serum triglyceride and cholesterol levels. Analysis of insulin receptor related signaling in the liver of adult fasted pigs revealed increased phosphorylation of IRS1 and PI3K. In agreement with the loss of GHR, phosphorylation of STAT5 was significantly reduced. In contrast, phosphorylation

  18. Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver

    Directory of Open Access Journals (Sweden)

    Arne Hinrichs

    2018-05-01

    Full Text Available Objective: Laron syndrome (LS is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR gene. To establish a large animal model for LS, pigs with GHR knockout (KO mutations were generated and characterized. Methods: CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs. Since the latter two groups were not significantly different in any parameter investigated, they were pooled as the GHR expressing control group. The characterization program included body and organ growth, body composition, endocrine and clinical-chemical parameters, as well as signaling studies in liver tissue. Results: GHR-KO pigs lacked GHR and had markedly reduced serum insulin-like growth factor 1 (IGF1 levels and reduced IGF-binding protein 3 (IGFBP3 activity but increased IGFBP2 levels. Serum GH concentrations were significantly elevated compared with control pigs. GHR-KO pigs had a normal birth weight. Growth retardation became significant at the age of five weeks. At the age of six months, the body weight of GHR-KO pigs was reduced by 60% compared with controls. Most organ weights of GHR-KO pigs were reduced proportionally to body weight. However, the weights of liver, kidneys, and heart were disproportionately reduced, while the relative brain weight was almost doubled. GHR-KO pigs had a markedly increased percentage of total body fat relative to body weight and displayed transient juvenile hypoglycemia along with decreased serum triglyceride and cholesterol levels. Analysis of insulin receptor related signaling in the liver of adult fasted pigs revealed increased phosphorylation of IRS1 and PI3K. In agreement with the loss of GHR, phosphorylation of STAT5 was

  19. Hepatitis Vaccines

    OpenAIRE

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

  20. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Donate Today Enroll in 123 What is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that causes temporary ...

  1. Iodine Deficiency

    Science.gov (United States)

    ... Fax/Phone Home » Iodine Deficiency Leer en Español Iodine Deficiency Iodine is an element that is needed ... world’s population remains at risk for iodine deficiency. Iodine Deficiency FAQs WHAT IS THE THYROID GLAND? The ...

  2. Analysis of complete nucleotide sequences of Angolan hepatitis B virus isolates reveals the existence of a separate lineage within genotype E.

    Directory of Open Access Journals (Sweden)

    Barbara V Lago

    Full Text Available Hepatitis B virus genotype E (HBV/E is highly prevalent in Western Africa. In this work, 30 HBV/E isolates from HBsAg positive Angolans (staff and visitors of a private hospital in Luanda were genetically characterized: 16 of them were completely sequenced and the pre-S/S sequences of the remaining 14 were determined. A high proportion (12/30, 40% of subjects tested positive for both HBsAg and anti-HBs markers. Deduced amino acid sequences revealed the existence of specific substitutions and deletions in the B- and T-cell epitopes of the surface antigen (pre-S1- and pre-S2 regions of the virus isolates derived from 8/12 individuals with concurrent HBsAg/anti-HBs. Phylogenetic analysis performed with 231 HBV/E full-length sequences, including 16 from this study, showed that all isolates from Angola, Namibia and the Democratic Republic of Congo (n = 28 clustered in a separate lineage, divergent from the HBV/E isolates from nine other African countries, namely Cameroon, Central African Republic, Côte d'Ivoire, Ghana, Guinea, Madagascar, Niger, Nigeria and Sudan, with a Bayesian posterior probability of 1. Five specific mutations, namely small S protein T57I, polymerase Q177H, G245W and M612L, and X protein V30L, were observed in 79-96% of the isolates of the separate lineage, compared to a frequency of 0-12% among the other HBV/E African isolates.

  3. Hepatitis B virus HBx protein localized to the nucleus restores HBx-deficient virus replication in HepG2 cells and in vivo in hydrodynamically-injected mice

    International Nuclear Information System (INIS)

    Keasler, Victor V.; Hodgson, Amanda J.; Madden, Charles R.; Slagle, Betty L.

    2009-01-01

    Identifying the requirements for the regulatory HBx protein in hepatitis B virus (HBV) replication is an important goal. A plasmid-based HBV replication assay was used to evaluate whether HBx subcellular localization influences its ability to promote virus replication, as measured by real time PCR quantitation of viral capsid-associated DNA. HBx targeted to the nucleus by a nuclear localization signal (NLS-HBx) was able to restore HBx-deficient HBV replication, while HBx containing a nuclear export signal (NES-HBx) was not. Both NLS-HBx and NES-HBx were expressed at similar levels (by immunoprecipitation and Western blotting), and proper localization of the signal sequence-tagged proteins was confirmed by deconvolution microscopy using HBx, NLS-HBx, and NES-HBx proteins fused to GFP. Importantly, these findings were confirmed in vivo by hydrodynamic injection into mice. Our results demonstrate that in these HBV replication assays, at least one function of HBx requires its localization to the nucleus.

  4. Global mRNA expression analysis in myosin II deficient strains of Saccharomyces cerevisiae reveals an impairment of cell integrity functions

    Directory of Open Access Journals (Sweden)

    Rivera-Molina Félix E

    2008-01-01

    Full Text Available Abstract Background The Saccharomyces cerevisiae MYO1 gene encodes the myosin II heavy chain (Myo1p, a protein required for normal cytokinesis in budding yeast. Myo1p deficiency in yeast (myo1Δ causes a cell separation defect characterized by the formation of attached cells, yet it also causes abnormal budding patterns, formation of enlarged and elongated cells, increased osmotic sensitivity, delocalized chitin deposition, increased chitin synthesis, and hypersensitivity to the chitin synthase III inhibitor Nikkomycin Z. To determine how differential expression of genes is related to these diverse cell wall phenotypes, we analyzed the global mRNA expression profile of myo1Δ strains. Results Global mRNA expression profiles of myo1Δ strains and their corresponding wild type controls were obtained by hybridization to yeast oligonucleotide microarrays. Results for selected genes were confirmed by real time RT-PCR. A total of 547 differentially expressed genes (p ≤ 0.01 were identified with 263 up regulated and 284 down regulated genes in the myo1Δ strains. Gene set enrichment analysis revealed the significant over-representation of genes in the protein biosynthesis and stress response categories. The SLT2/MPK1 gene was up regulated in the microarray, and a myo1Δslt2Δ double mutant was non-viable. Overexpression of ribosomal protein genes RPL30 and RPS31 suppressed the hypersensitivity to Nikkomycin Z and increased the levels of phosphorylated Slt2p in myo1Δ strains. Increased levels of phosphorylated Slt2p were also observed in wild type strains under these conditions. Conclusion Following this analysis of global mRNA expression in yeast myo1Δ strains, we conclude that 547 genes were differentially regulated in myo1Δ strains and that the stress response and protein biosynthesis gene categories were coordinately regulated in this mutant. The SLT2/MPK1 gene was confirmed to be essential for myo1Δ strain viability, supporting that the up

  5. An RNA-Seq Transcriptome Analysis of Orthophosphate-Deficient White Lupin Reveals Novel Insights into Phosphorus Acclimation in Plants1[W][OA

    Science.gov (United States)

    O’Rourke, Jamie A.; Yang, S. Samuel; Miller, Susan S.; Bucciarelli, Bruna; Liu, Junqi; Rydeen, Ariel; Bozsoki, Zoltan; Uhde-Stone, Claudia; Tu, Zheng Jin; Allan, Deborah; Gronwald, John W.; Vance, Carroll P.

    2013-01-01

    Phosphorus, in its orthophosphate form (Pi), is one of the most limiting macronutrients in soils for plant growth and development. However, the whole-genome molecular mechanisms contributing to plant acclimation to Pi deficiency remain largely unknown. White lupin (Lupinus albus) has evolved unique adaptations for growth in Pi-deficient soils, including the development of cluster roots to increase root surface area. In this study, we utilized RNA-Seq technology to assess global gene expression in white lupin cluster roots, normal roots, and leaves in response to Pi supply. We de novo assembled 277,224,180 Illumina reads from 12 complementary DNA libraries to build what is to our knowledge the first white lupin gene index (LAGI 1.0). This index contains 125,821 unique sequences with an average length of 1,155 bp. Of these sequences, 50,734 were transcriptionally active (reads per kilobase per million reads ≥ 3), representing approximately 7.8% of the white lupin genome, using the predicted genome size of Lupinus angustifolius as a reference. We identified a total of 2,128 sequences differentially expressed in response to Pi deficiency with a 2-fold or greater change and P ≤ 0.05. Twelve sequences were consistently differentially expressed due to Pi deficiency stress in three species, Arabidopsis (Arabidopsis thaliana), potato (Solanum tuberosum), and white lupin, making them ideal candidates to monitor the Pi status of plants. Additionally, classic physiological experiments were coupled with RNA-Seq data to examine the role of cytokinin and gibberellic acid in Pi deficiency-induced cluster root development. This global gene expression analysis provides new insights into the biochemical and molecular mechanisms involved in the acclimation to Pi deficiency. PMID:23197803

  6. Analyses of Selenotranscriptomes and Selenium Concentrations in Response to Dietary Selenium Deficiency and Age Reveal Common and Distinct Patterns by Tissue and Sex in Telomere-Dysfunctional Mice.

    Science.gov (United States)

    Cao, Lei; Zhang, Li; Zeng, Huawei; Wu, Ryan Ty; Wu, Tung-Lung; Cheng, Wen-Hsing

    2017-10-01

    Background: The hierarchies of tissue selenium distribution and selenotranscriptomes are thought to critically affect healthspan and longevity. Objective: We determined selenium status and selenotranscriptomes in response to long-term dietary selenium deficiency and age in tissues of male and female mice. Methods: Weanling telomerase RNA component knockout C57BL/6 mice were fed a selenium-deficient (0.03 mg Se/kg) Torula yeast-based AIN-93G diet or a diet supplemented with sodium selenate (0.15 mg Se/kg) until age 18 or 24 mo. Plasma, hearts, kidneys, livers, and testes were collected to assay for selenotranscriptomes, selected selenoproteins, and tissue selenium concentrations. Data were analyzed with the use of 2-factor ANOVA (diet × age) in both sexes. Results: Dietary selenium deficiency decreased ( P ≤ 0.05) selenium concentrations (65-72%) and glutathione peroxidase (GPX) 3 (82-94%) and selenoprotein P (SELENOP) (17-41%) levels in the plasma of both sexes of mice and mRNA levels (9-68%) of 4, 4, and 12 selenoproteins in the heart, kidney, and liver of males, respectively, and 5, 16, and 14 selenoproteins, respectively, in females. Age increased selenium concentrations and SELENOP levels (27% and 30%, respectively; P ≤ 0.05) in the plasma of males only but decreased (12-46%; P selenium deficiency and age in ≥1 tissue or sex, or both. Dietary selenium deficiency upregulated (40-160%; P ≤ 0.05) iodothyronine deiodinase 2 ( Dio2 ) and selenoprotein N ( Selenon ) in the kidneys of males. Age upregulated (11-44%; P selenium status and selenotranscriptomes because of dietary selenium deficiency and age. © 2017 American Society for Nutrition.

  7. Hepatitis C: Managing Pain

    Science.gov (United States)

    ... Pain: Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans and the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting ...

  8. IDH2 Deficiency Aggravates Fructose-Induced NAFLD by Modulating Hepatic Fatty Acid Metabolism and Activating Inflammatory Signaling in Female Mice

    Directory of Open Access Journals (Sweden)

    Jeong Hoon Pan

    2018-05-01

    Full Text Available Fructose is a strong risk factor for non-alcoholic fatty liver disease (NAFLD, resulting from the disruption of redox systems by excessive reactive oxygen species production in the liver cells. Of note, recent epidemiological studies indicated that women are more prone to developing metabolic syndrome in response to fructose-sweetened beverages. Hence, we examined whether disruption of the redox system through a deletion of NADPH supplying mitochondrial enzyme, NADP+-dependent isocitrate dehydrogenase (IDH2, exacerbates fructose-induced NAFLD conditions in C57BL/6 female mice. Wild-type (WT and IDH2 knockout (KO mice were treated with either water or 34% fructose water over six weeks. NAFLD phenotypes and key proteins and mRNAs involved in the inflammatory pathway (e.g., NF-κB p65 and IL-1β were assessed. Hepatic lipid accumulation was significantly increased in IDH2 KO mice fed fructose compared to the WT counterpart. Neutrophil infiltration was observed only in IDH2 KO mice fed fructose. Furthermore, phosphorylation of NF-κB p65 and expression of IL-1β was remarkably upregulated in IDH2 KO mice fed fructose, and expression of IκBα was decreased by fructose treatment in both WT and IDH2 KO groups. For the first time, we report our novel findings that IDH2 KO female mice may be more susceptible to fructose-induced NAFLD and the associated inflammatory response, suggesting a mechanistic role of IDH2 in metabolic diseases.

  9. RNA-sequencing and pathway analysis reveal alteration of hepatic steroid biosynthesis and retinol metabolism by tributyltin exposure in male rare minnow (Gobiocypris rarus).

    Science.gov (United States)

    Zhang, Jiliang; Zhang, Chunnuan; Sun, Ping; Huang, Maoxian; Fan, Mingzhen; Liu, Min

    2017-07-01

    Tributyltin (TBT) is widely spread in aquatic ecosystems. Although adverse effects of TBT on reproduction and lipogenesis are observed in fishes, the underlying mechanisms, especially in livers, are still scarce and inconclusive. Thus, RNA-sequencing runs were performed on the hepatic libraries of adult male rare minnow (Gobiocypris rarus) after TBT exposure for 60d. After differentially expressed genes were identified, enrichment analysis and validation by quantitative real-time PCR were conducted. The results showed that TBT up-regulated the profile of hepatic genes in the steroid biosynthesis pathway and down-regulated the profile of hepatic genes in the retinol metabolism pathway. In the hepatic steroid biosynthesis pathway, TBT might induce biosynthesis of cholesterol, which could affect the bioavailability of steroid hormones. More important, 3beta-hydroxysteroid 3-dehydrogenase, a key enzyme in the biosynthesis of all active steroid hormones, was up-regulated by TBT exposure. In the hepatic retinol metabolism pathway, TBT impaired retinoic acid homeostasis which plays essential roles in both reproduction and lipogenesis. The results of two pathways offered new mechanisms underlying the toxicology of TBT and represented a starting point from which detailed mechanistic links should be explored. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effects of Fe and Mn deficiencies on the protein profiles of tomato (Solanum lycopersicum) xylem sap as revealed by shotgun analyses

    Science.gov (United States)

    The aim of this work was to study the effects of Fe and Mn deficiencies on the xylem sap proteome of tomato using a shotgun proteomic approach, with the final goal of elucidating plant response mechanisms to these stresses. This approach yielded 643 proteins reliably identified and quantified with 7...

  11. Health Deficiencies

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of all health deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection date,...

  12. [History of viral hepatitis].

    Science.gov (United States)

    Fonseca, José Carlos Ferraz da

    2010-01-01

    The history of viral hepatitis goes back thousands of years and is a fascinating one. When humans were first infected by such agents, a natural repetitive cycle began, with the capacity to infect billions of humans, thus decimating the population and causing sequelae in thousands of lives. This article reviews the available scientific information on the history of viral hepatitis. All the information was obtained through extensive bibliographic review, including original and review articles and consultations on the internet. There are reports on outbreaks of jaundice epidemics in China 5,000 years ago and in Babylon more than 2,500 years ago. The catastrophic history of great jaundice epidemics and pandemics is well known and generally associated with major wars. In the American Civil War, 40,000 cases occurred among Union troops. In 1885, an outbreak of catarrhal jaundice affected 191 workers at the Bremen shipyard (Germany) after vaccination against smallpox. In 1942, 28,585 soldiers became infected with hepatitis after inoculation with the yellow fever vaccine. The number of cases of hepatitis during the Second World War was estimated to be 16 million. Only in the twentieth century were the main agents causing viral hepatitis identified. The hepatitis B virus was the first to be discovered. In this paper, through reviewing the history of major epidemics caused by hepatitis viruses and the history of discovery of these agents, singular peculiarities were revealed. Examples of this include the accidental or chance discovery of the hepatitis B and D viruses.

  13. NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Vikram, E-mail: prasadvm@ucmail.uc.edu [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Chirra, Shivani [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Kohli, Rohit [Department of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH 45267 (United States); Shull, Gary E. [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States)

    2014-07-25

    Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na{sup +}/H{sup +} exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors.

  14. NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Prasad, Vikram; Chirra, Shivani; Kohli, Rohit; Shull, Gary E.

    2014-01-01

    Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na + /H + exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors

  15. Hepatitis E nu ook in Nederland

    NARCIS (Netherlands)

    van der Pal, H. J.; Jansen, P. L.

    1992-01-01

    A case report of a male aged 31 who, after a journey to Bangladesh, returned with a disease resembling acute hepatitis A. Closer study revealed a hepatitis E infection. He recovered in slightly over two weeks

  16. CLINICAL FEATURES OF REFRACTORY FORMS OF ANEMIA IN CHILDREN WITH CHRONIC HEPATITIS В

    Directory of Open Access Journals (Sweden)

    F. I. Inoyаtova

    2013-01-01

    Full Text Available Examination of 125 children with chronic hepatitis В and concomitant anemia has determined the frequency of refractory forms of anemia (52,5%. The disease progressed more severely on the background of anemia, which was indicated by the prevalence of CHВ forms with severe activity (71,4%. The pathognomonic symptoms of anemic processes were revealed. Two pathogenetic variants of the anemia genesis in children with CHВ are being considered: the first is defined by veritable iron deficiency with ferrokinetic markers of iron-deficiency anemia; the second — by relocationable iron deficit that is typical for hemosiderosis and refractoriness development.

  17. Proteomic analysis of Arabidopsis thaliana leaves in response to acute boron deficiency and toxicity reveals effects on photosynthesis, carbohydrate metabolism, and protein synthesis.

    Science.gov (United States)

    Chen, Mei; Mishra, Sasmita; Heckathorn, Scott A; Frantz, Jonathan M; Krause, Charles

    2014-02-15

    Boron (B) stress (deficiency and toxicity) is common in plants, but as the functions of this essential micronutrient are incompletely understood, so too are the effects of B stress. To investigate mechanisms underlying B stress, we examined protein profiles in leaves of Arabidopsis thaliana plants grown under normal B (30 μM), compared to plants transferred for 60 and 84 h (i.e., before and after initial visible symptoms) in deficient (0 μM) or toxic (3 mM) levels of B. B-responsive polypeptides were sequenced by mass spectrometry, following 2D gel electrophoresis, and 1D gels and immunoblotting were used to confirm the B-responsiveness of some of these proteins. Fourteen B-responsive proteins were identified, including: 9 chloroplast proteins, 6 proteins of photosynthetic/carbohydrate metabolism (rubisco activase, OEC23, photosystem I reaction center subunit II-1, ATPase δ-subunit, glycolate oxidase, fructose bisphosphate aldolase), 6 stress proteins, and 3 proteins involved in protein synthesis (note that the 14 proteins may fall into multiple categories). Most (8) of the B-responsive proteins decreased under both B deficiency and toxicity; only 3 increased with B stress. Boron stress decreased, or had no effect on, 3 of 4 oxidative stress proteins examined, and did not affect total protein. Hence, our results indicate relatively early specific effects of B stress on chloroplasts and protein synthesis. Copyright © 2013 Elsevier GmbH. All rights reserved.

  18. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... friend, spouse, life partner, parent, sibling or other family member. What is HE? Hepatic Encephalopathy, sometimes referred ... disease is. It’s important for you and your family to become familiar with the signs of Hepatic ...

  19. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Your Story Spread the Word Give While You Shop Contact Us Donate Now Hepatic Encephalopathy Back Hepatic ... Your Story Spread the Word Give While You Shop Contact Us Donate Now Help ALF Improve This ...

  20. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Now Hepatic Encephalopathy Back Hepatic Encephalopathy is a brain disorder that develops in some individuals with liver ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ...

  1. Transmission of clonal hepatitis C virus genomes reveals the dominant but transitory role of CD8¿ T cells in early viral evolution

    DEFF Research Database (Denmark)

    Callendret, Benoît; Bukh, Jens; Eccleston, Heather B

    2011-01-01

    occurred slowly over several years of chronic infection. Together these observations indicate that during acute hepatitis C, virus evolution was driven primarily by positive selection pressure exerted by CD8(+) T cells. This influence of immune pressure on viral evolution appears to subside as chronic......The RNA genome of the hepatitis C virus (HCV) diversifies rapidly during the acute phase of infection, but the selective forces that drive this process remain poorly defined. Here we examined whether Darwinian selection pressure imposed by CD8(+) T cells is a dominant force driving early amino acid...... replacement in HCV viral populations. This question was addressed in two chimpanzees followed for 8 to 10 years after infection with a well-defined inoculum composed of a clonal genotype 1a (isolate H77C) HCV genome. Detailed characterization of CD8(+) T cell responses combined with sequencing of recovered...

  2. Alcohol and Hepatitis

    Science.gov (United States)

    ... Home » Living with Hepatitis » Daily Living: Alcohol Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... heavy drinking, most heavy drinkers have developed cirrhosis. Hepatitis C and cirrhosis In general, someone with hepatitis ...

  3. Hepatitis C: Treatment

    Science.gov (United States)

    ... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

  4. Full-Length Characterization of Hepatitis C Virus Subtype 3a Reveals Novel Hypervariable Regions under Positive Selection during Acute Infection▿

    OpenAIRE

    Humphreys, Isla; Fleming, Vicki; Fabris, Paolo; Parker, Joe; Schulenberg, Bodo; Brown, Anthony; Demetriou, Charis; Gaudieri, Silvana; Pfafferott, Katja; Lucas, Michaela; Collier, Jane; Huang, Kuan-Hsiang Gary; Pybus, Oliver G.; Klenerman, Paul; Barnes, Eleanor

    2009-01-01

    Hepatitis C virus subtype 3a is a highly prevalent and globally distributed strain that is often associated with infection via injection drug use. This subtype exhibits particular phenotypic characteristics. In spite of this, detailed genetic analysis of this subtype has rarely been performed. We performed full-length viral sequence analysis in 18 patients with chronic HCV subtype 3a infection and assessed genomic viral variability in comparison to other HCV subtypes. Two novel regions of int...

  5. Hepatitis C

    Science.gov (United States)

    ... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...

  6. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is Important The Connection Between HE and Liver ... Why it’s Important to Treat HE Symptoms of Liver Failure Glossary of terms ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

  7. Hepatic Encephalopathy

    Science.gov (United States)

    ... Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is Important The Connection Between HE and Liver ... Why it’s Important to Treat HE Symptoms of Liver Failure Glossary of terms ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

  8. Hepatitis A

    Science.gov (United States)

    ... is an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... suggest medicines to help relieve your symptoms. The hepatitis A vaccine can prevent HAV. Good hygiene can also ...

  9. Insertional mutagenesis in mice deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 reveals cancer gene interactions and correlations with tumor phenotypes

    DEFF Research Database (Denmark)

    Kool, Jaap; Uren, Anthony G; Martins, Carla P

    2010-01-01

    -throughput murine leukemia virus insertional mutagenesis screens in mice that are deficient for one or two CDK inhibitors. We retrieved 9,117 retroviral insertions from 476 lymphomas to define hundreds of loci that are mutated more frequently than expected by chance. Many of these loci are skewed toward a specific...... revealed a significant overlap between the datasets. Together, our findings highlight the importance of genetic context within large-scale mutation detection studies, and they show a novel use for insertional mutagenesis data in prioritizing disease-associated genes that emerge from genome-wide association...

  10. Hypoksisk hepatitis

    DEFF Research Database (Denmark)

    Amadid, Hanan; Schiødt, Frank Vinholt

    2014-01-01

    Hypoxic hepatitis (HH), also known as ischaemic hepatitis or shock liver, is an acute liver injury caused by hepatic hypoxia. Cardiac failure, respiratory failure and septic shock are the main underlying conditions. In each of these conditions, several haemodynamic mechanisms lead to hepatic...... hypoxia. A shock state is observed in only 50% of cases. Thus, shock liver and ischaemic hepatitis are misnomers. HH can be a diagnostic pitfall but the diagnosis can be established when three criteria are met. Prognosis is poor and prompt identification and treatment of the underlying conditions...

  11. Structural characterization of a mixed-linkage glucan deficient mutant reveals alteration in cellulose microfibril orientation in rice coleoptile mesophyll cell walls

    Directory of Open Access Journals (Sweden)

    Andreia Michelle Smith-Moritz

    2015-08-01

    Full Text Available The CELLULOSE SYNTHASE-LIKE F6 (CslF6 gene was previously shown to mediate the biosynthesis of mixed-linkage glucan (MLG, a cell wall polysaccharide that is hypothesized to be a tightly associated with cellulose and also have a role in cell expansion in the primary cell wall of young seedlings in grass species. We have recently shown that loss-of-function cslf6 rice mutants do not accumulate MLG in most vegetative tissues. Despite the absence of a structurally important polymer, MLG, these mutants are unexpectedly viable and only show a moderate growth compromise compared to wild type. Therefore these mutants are ideal biological systems to test the current grass cell wall model. In order to gain a better understanding of the role of MLG in the primary wall, we performed in-depth compositional and structural analyses of the cell walls of three day-old rice seedlings using various biochemical and novel microspectroscopic approaches. We found that cellulose content as well as matrix polysaccharide composition was not significantly altered in the MLG deficient mutant. However, we observed a significant change in cellulose microfibril bundle organization in mesophyll cell walls of the cslf6 mutant. Using synchrotron source Fourier Transform Mid-Infrared Spectromicroscopy for high-resolution imaging, we determined that the bonds associated with cellulose and arabinoxylan, another major component of the primary cell was of grasses, were in a lower energy configuration compared to wild type, suggesting a slightly weaker primary wall in MLG deficient mesophyll cells. Taken together, these results suggest that MLG may influence cellulose deposition in mesophyll cell walls without significantly affecting anisotropic growth thus challenging MLG importance in cell wall expansion.

  12. Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR knockout mice: implications on anti-glucagon therapies for diabetes

    Directory of Open Access Journals (Sweden)

    Molloy Mark P

    2011-06-01

    Full Text Available Abstract Background Glucagon is an important hormone in the regulation of glucose homeostasis, particularly in the maintenance of euglycemia and prevention of hypoglycemia. In type 2 Diabetes Mellitus (T2DM, glucagon levels are elevated in both the fasted and postprandial states, which contributes to inappropriate hyperglycemia through excessive hepatic glucose production. Efforts to discover and evaluate glucagon receptor antagonists for the treatment of T2DM have been ongoing for approximately two decades, with the challenge being to identify an agent with appropriate pharmaceutical properties and efficacy relative to potential side effects. We sought to determine the hepatic & systemic consequence of full glucagon receptor antagonism through the study of the glucagon receptor knock-out mouse (Gcgr-/- compared to wild-type littermates. Results Liver transcriptomics was performed using Affymetric expression array profiling, and liver proteomics was performed by iTRAQ global protein analysis. To complement the transcriptomic and proteomic analyses, we also conducted metabolite profiling (~200 analytes using mass spectrometry in plasma. Overall, there was excellent concordance (R = 0.88 for changes associated with receptor knock-out between the transcript and protein analysis. Pathway analysis tools were used to map the metabolic processes in liver altered by glucagon receptor ablation, the most notable being significant down-regulation of gluconeogenesis, amino acid catabolism, and fatty acid oxidation processes, with significant up-regulation of glycolysis, fatty acid synthesis, and cholesterol biosynthetic processes. These changes at the level of the liver were manifested through an altered plasma metabolite profile in the receptor knock-out mice, e.g. decreased glucose and glucose-derived metabolites, and increased amino acids, cholesterol, and bile acid levels. Conclusions In sum, the results of this study suggest that the complete ablation

  13. Mutational Analysis of the Hypervariable Region of Hepatitis E Virus Reveals Its Involvement in the Efficiency of Viral RNA Replication ▿

    OpenAIRE

    Pudupakam, R. S.; Kenney, Scott P.; Córdoba, Laura; Huang, Yao-Wei; Dryman, Barbara A.; LeRoith, Tanya; Pierson, F. William; Meng, Xiang-Jin

    2011-01-01

    The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication...

  14. Iodine Deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.

    2009-01-01

    Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected.

  15. Hepatitis A through E (Viral Hepatitis)

    Science.gov (United States)

    ... Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

  16. Hepatitis Vaccines

    Directory of Open Access Journals (Sweden)

    Sina Ogholikhan

    2016-03-01

    Full Text Available Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver.

  17. Hepatitis Vaccines

    Science.gov (United States)

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  18. Analysis of meiosis in SUN1 deficient mice reveals a distinct role of SUN2 in mammalian meiotic LINC complex formation and function.

    Directory of Open Access Journals (Sweden)

    Jana Link

    2014-02-01

    Full Text Available LINC complexes are evolutionarily conserved nuclear envelope bridges, composed of SUN (Sad-1/UNC-84 and KASH (Klarsicht/ANC-1/Syne/homology domain proteins. They are crucial for nuclear positioning and nuclear shape determination, and also mediate nuclear envelope (NE attachment of meiotic telomeres, essential for driving homolog synapsis and recombination. In mice, SUN1 and SUN2 are the only SUN domain proteins expressed during meiosis, sharing their localization with meiosis-specific KASH5. Recent studies have shown that loss of SUN1 severely interferes with meiotic processes. Absence of SUN1 provokes defective telomere attachment and causes infertility. Here, we report that meiotic telomere attachment is not entirely lost in mice deficient for SUN1, but numerous telomeres are still attached to the NE through SUN2/KASH5-LINC complexes. In Sun1(-/- meiocytes attached telomeres retained the capacity to form bouquet-like clusters. Furthermore, we could detect significant numbers of late meiotic recombination events in Sun1(-/- mice. Together, this indicates that even in the absence of SUN1 telomere attachment and their movement within the nuclear envelope per se can be functional.

  19. Skeletal muscle microRNA and messenger RNA profiling in cofilin-2 deficient mice reveals cell cycle dysregulation hindering muscle regeneration.

    Directory of Open Access Journals (Sweden)

    Sarah U Morton

    Full Text Available Congenital myopathies are rare skeletal muscle diseases presenting in early age with hypotonia and weakness often linked to a genetic defect. Mutations in the gene for cofilin-2 (CFL2 have been identified in several families as a cause of congenital myopathy with nemaline bodies and cores. Here we explore the global messenger and microRNA expression patterns in quadriceps muscle samples from cofillin-2-null mice and compare them with sibling-matched wild-type mice to determine the molecular pathways and mechanisms involved. Cell cycle processes are markedly dysregulated, with altered expression of genes involved in mitotic spindle formation, and evidence of loss of cell cycle checkpoint regulation. Importantly, alterations in cell cycle, apoptosis and proliferation pathways are present in both mRNA and miRNA expression patterns. Specifically, p21 transcript levels were increased, and the expression of p21 targets, such as cyclin D and cyclin E, was decreased. We therefore hypothesize that deficiency of cofilin-2 is associated with interruption of the cell cycle at several checkpoints, hindering muscle regeneration. Identification of these pathways is an important step towards developing appropriate therapies against various congenital myopathies.

  20. Hepatic Lipodystrophy in Galloway Calves.

    Science.gov (United States)

    Wieland, M; Mann, S; Hafner-Marx, A; Ignatius, A; Metzner, M

    2017-05-01

    Hepatic lipodystrophy in Galloway calves is a fatal liver disease affecting a small proportion of the Galloway breed described in different parts of Europe and North America during the past decades. The clinical findings include a diversity of neurological signs. Clinical pathology findings frequently indicate hepatobiliary disease. Postmortem examination reveals an enlarged, pale yellow, and firm liver. Histologic lesions include hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. To date, the etiopathogenesis remains obscure. Infectious causes, intoxications, and a hereditary origin have been considered. We describe hepatic lipodystrophy in Galloway calves from an extensively farmed cow-calf operation in southern Germany. Main clinical findings in 6 calves were consistent with hepatic encephalopathy. Clinical pathology findings in 5 of 6 tested animals revealed increased concentration of total bilirubin (maximum value [MV], 54 μmol/l; reference range [RR], 250 U/g Hb). Postmortem examination in 6 calves revealed a firm, diffusely enlarged yellow liver with a finely nodular surface. Histologic lesions included hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. Our findings add to the existing data on hepatic lipodystrophy in the Galloway breed and outline a protocol to aid in the diagnosis of this disorder.

  1. Feature Hepatitis: Hepatitis Can Strike Anyone

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis Can Strike Anyone Past Issues / Spring 2009 Table ... from all walks of life are affected by hepatitis, especially hepatitis C, the most common form of ...

  2. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Plan Long-Term Considerations Patient Support Finding Support Services Peer Support Groups Financial Assistance Support for My ... is Hepatic Encephalopathy? Why Your Liver is ...

  3. Travelers' Health: Hepatitis C

    Science.gov (United States)

    ... Chapter 3 - Hepatitis B Chapter 3 - Hepatitis E Hepatitis C Deborah Holtzman INFECTIOUS AGENT Hepatitis C virus ( ... mother to child. Map 3-05. Prevalence of hepatitis C virus infection 1 PDF Version (printable) 1 ...

  4. Travelers' Health: Hepatitis A

    Science.gov (United States)

    ... 3 - Helminths, Soil-Transmitted Chapter 3 - Hepatitis B Hepatitis A Noele P. Nelson INFECTIOUS AGENT Hepatitis A ... hepatitis/HAV Table 3-02. Vaccines to prevent hepatitis A VACCINE TRADE NAME (MANUFACTURER) AGE (Y) DOSE ...

  5. Hepatitis (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hepatitis KidsHealth / For Parents / Hepatitis Print en español Hepatitis What Is Hepatitis? Hepatitis is an inflammation of the liver. The ...

  6. Travelers' Health: Hepatitis B

    Science.gov (United States)

    ... Chapter 3 - Hepatitis A Chapter 3 - Hepatitis C Hepatitis B Francisco Averhoff INFECTIOUS AGENT Hepatitis B virus ( ... progression of disease. Map 3-04. Prevalence of hepatitis B virus infection 1 PDF Version (printable) 1 ...

  7. Hepatitis C: Clinical Trials

    Science.gov (United States)

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  8. Hepatitis C: Mental Health

    Science.gov (United States)

    ... the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting Tested Just Diagnosed Treatment Choice Program ... Pain Mental Health Sex and Sexuality (for Hepatitis C) Success Stories FAQs For Health Care Providers Provider ...

  9. Cobalt-deficiency-induced hyperhomocysteinaemia and oxidative status of cattle.

    Science.gov (United States)

    Stangl, G I; Schwarz, F J; Jahn, B; Kirchgessner, M

    2000-01-01

    In ruminants, Co is required for the synthesis of vitamin B12, which in turn is needed for the resynthesis of methionine by methylation of homocysteine and thus, cobalamin deficiency may induce hyperhomocysteinaemia which is brought into context with perturbations of the antioxidative-prooxidative balance. The present study was conducted to explore whether Co deficiency in cattle is also associated with homocysteine-induced disturbances of oxidative status. Co deficiency was induced in cattle by feeding two groups of animals on either a basal maize-silage-based diet that was moderately low in Co (83 micrograms Co/kg DM), or the same diet supplemented with Co to a total of 200 micrograms Co/kg DM, for 43 weeks. Co deficiency was apparent from a reduced vitamin B12 status in serum and liver and an accumulation of homocysteine in plasma which was in excess of 4.8 times higher in Co-deprived cattle than in controls. The much increased level of circulating homocysteine did not indicate severe disturbances in antioxidant-prooxidant balance as measured by individual markers of lipid peroxidation, protein oxidation, and the antioxidative defence system. There were no quantitative difference in plasma thiol groups, nor were there significant changes in concentrations of alpha-tocopherol, microsomal thiobarbituric acid-reactive substances and carbonyl groups in liver. However, there was a trend toward increased plasma carbonyl levels indicating a slight degradation of plasma proteins in the hyperhomocysteinaemic cattle. Analysis of the hepatic catalase (EC 1.11.1.6) activity revealed an 11% reduction in Co-deficient cattle relative to the controls. These results indicate that long-term moderate Co deficiency may induce a severe accumulation of plasma homocysteine in cattle, but considerable abnormalities in oxidative status failed to appear.

  10. Sulfur amino acids metabolism in magnesium deficient rats

    Energy Technology Data Exchange (ETDEWEB)

    Tojo, H.; Kosokawa, Y.; Yamaguchi, K.

    1984-01-01

    Effect of magnesium (Mg) deficiency on sulfur amino acid metabolism was investigated in rats. Young male rats were fed on the diet containing either 2.26 (deficient rats) or 63.18 mg Mg/100g diet (control and low protein rats) for 2 weeks. A remarkable decrease of body weight gain, serum Mg contents and a slight decreases in the hematological parameters such as Hb, Ht and RBC was observed, while the hepatic Mg and Ca was not significantly changed. Erythema and cramps were observed 5 days after feeding on the Mg-depleted diet. The hepatic glutathione and cysteine contents increased in Mg-deficient rats. However, no significant change of cysteine dioxygenase (CDO) activity and taurine content in Mg-deficient rat liver was observed. These results suggest that Mg deficiency affects the utilization and biosynthesis of hepatic glutathione but not the cysteine catabolism.

  11. Immigration and viral hepatitis

    NARCIS (Netherlands)

    S. Sharma (Suraj); M. Carballo (Manuel); J.J. Feld (Jordan J.); H.L.A. Janssen (Harry)

    2015-01-01

    textabstractWHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and

  12. Mapping of a Cellulose-Deficient Mutant Named dwarf1-1 in Sorghum bicolor to the Green Revolution Gene gibberellin20-oxidase Reveals a Positive Regulatory Association between Gibberellin and Cellulose Biosynthesis.

    Science.gov (United States)

    Petti, Carloalberto; Hirano, Ko; Stork, Jozsef; DeBolt, Seth

    2015-09-01

    Here, we show a mechanism for expansion regulation through mutations in the green revolution gene gibberellin20 (GA20)-oxidase and show that GAs control biosynthesis of the plants main structural polymer cellulose. Within a 12,000 mutagenized Sorghum bicolor plant population, we identified a single cellulose-deficient and male gametophyte-dysfunctional mutant named dwarf1-1 (dwf1-1). Through the Sorghum propinquum male/dwf1-1 female F2 population, we mapped dwf1-1 to a frameshift in GA20-oxidase. Assessment of GAs in dwf1-1 revealed ablation of GA. GA ablation was antagonistic to the expression of three specific cellulose synthase genes resulting in cellulose deficiency and growth dwarfism, which were complemented by exogenous bioactive gibberellic acid application. Using quantitative polymerase chain reaction, we found that GA was positively regulating the expression of a subset of specific cellulose synthase genes. To cross reference data from our mapped Sorghum sp. allele with another monocotyledonous plant, a series of rice (Oryza sativa) mutants involved in GA biosynthesis and signaling were isolated, and these too displayed cellulose deficit. Taken together, data support a model whereby suppressed expansion in green revolution GA genes involves regulation of cellulose biosynthesis. © 2015 American Society of Plant Biologists. All Rights Reserved.

  13. Alcoholic Hepatitis

    Science.gov (United States)

    ... yellow color. Confusion, drowsiness and slurred speech (hepatic encephalopathy). A damaged liver has trouble removing toxins from your body. The ... of toxins can damage your brain. Severe hepatic encephalopathy can result in ... of the liver frequently leads to liver failure. Kidney failure. A ...

  14. Hepatitis E virus infection in central China reveals no evidence of cross-species transmission between human and swine in this area.

    Directory of Open Access Journals (Sweden)

    Wen Zhang

    Full Text Available Hepatitis E virus (HEV is a zoonotic pathogen of which several species of animal were reported as reservoirs. Swine stands out as the major reservoir for HEV infection in humans, as suggested by the close genetic relationship of swine and human virus. Since 2000, Genotype 4 HEV has become the dominant cause of hepatitis E disease in China. Recent reports showed that genotype 4 HEV is freely transmitted between humans and swine in eastern and southern China. However, the infection status of HEV in human and swine populations in central China is still unclear. This study was conducted in a rural area of central China, where there are many commercial swine farms. A total of 1476 serum and 554 fecal specimens were collected from the general human and swine populations in this area, respectively. The seroepidemiological study was conducted by enzyme-linked immunosorbent assay. Conserved genomic sequences of open reading frame 2 were detected using reverse transcription-PCR. The results indicated that the overall viral burden of the general human subjects was 0.95% (14/1476, while 7.0% (39/554 of the swine excreted HEV in stool. The positive rate of anti-HEV IgG and IgM in the serum samples was 7.9% (117/1476 and 1.6% (24/1476, respectively. Phylogenetic analysis based on the 150 nt partial sequence of the capsid protein gene showed that the 53 swine and human HEV isolates in the current study all belonged to genotype 4, clustering into three major groups. However, the HEV isolates prevalent in the human and swine populations were classified into known distinct subgenotypes, which suggested that no cross-species transmission between swine and humans had taken place in this area. This result was confirmed by cloning and phylogenetic analysis of the complete capsid protein gene sequence of three representative HEV strains in the three major groups. The cross reactivity between anti-HEV IgG from human sera and the two representative strains from swine in

  15. Antepartum Ornithine Transcarbamylase Deficiency

    Directory of Open Access Journals (Sweden)

    Hitoshi Nakajima

    2014-11-01

    Full Text Available Ornithine transcarbamylase deficiency (OTCD is the most common type urea cycle enzyme deficiencies. This syndrome results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase, which catalyzes the conversion of ornithine and carbamoyl phosphate to citrullin. Our case was a 28-year-old female diagnosed with OTCD following neurocognitive deficit during her first pregnancy. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. Plasma amino acid and urine organic acid analysis revealed OTCD. After combined modality treatment with arginine, sodium benzoate and hemodialysis, the patient's plasma ammonia level stabilized and her mental status returned to normal. At last she recovered without any damage left.

  16. Primary hepatic pheochromocytoma

    International Nuclear Information System (INIS)

    Rimmelin, A.; Hartheiser, M.; Gangi, A.; Welsch, M.; Jeung, M.Y.; Jaeck, D.; Tongio, J.; Dietemann, J.L.

    1996-01-01

    Pheochromocytomas are uncommon tumors that represent a potentially curable cause of hypertension. They are usually located in the adrenal glands, but 10% arise from extra-adrenal sites, located along the paravertebral sympathetic chains. We report a case of primary hepatic pheochromocytoma responsible for a severe hypertension in a 24-year-old man. Echotomography showed a lightly heterogeneous mass located in the segment 8 of the liver. Iodine 131 -metaiodobenzylguanidine scintigraphy showed a large hepatic concentration of the tracer and no other localization. This tumor appeared highly vascularized on enhanced CT scan and on aortic angiography. Magnetic resonance imaging revealed a hepatic tumor with a high signal intensity on T2-weighted images and with a signal isointense to the liver on T1-weighted images. The hepatic venous sampling contained the highest catecholamine level, whereas the adrenal venous samping was normal. After surgical resection of the hepatic tumor, the tension level and catecholamines plasmatic level normalized. No recurrent symptoms appeared during a 3-year follow-up. (orig.)

  17. Subtype Specific Differences in NS5A Domain II Reveals Involvement of Proline at Position 310 in Cyclosporine Susceptibility of Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Israr-ul H. Ansari

    2012-11-01

    Full Text Available Hepatitis C virus (HCV is susceptible to cyclosporine (CsA and other cyclophilin (CypA inhibitors, but the genetic basis of susceptibility is controversial. Whether genetic variation in NS5A alters cell culture susceptibility of HCV to CypA inhibition is unclear. We constructed replicons containing NS5A chimeras from genotypes 1a, 2a and 4a to test how variation in carboxy terminal regions of NS5A altered the genotype 1b CsA susceptibility. All chimeric replicons including genotype 1b Con1LN-wt replicon exhibited some cell culture sensitivity to CsA with genotype 4a being most sensitive and 1a the least. The CypA binding pattern of truncated NS5A genotypes correlated with the susceptibility of these replicons to CsA. The Con1LN-wt replicon showed increased susceptibility towards CsA when proline at position 310P was mutated to either threonine or alanine. Furthermore, a 15 amino acid long peptide fused N terminally to GFP coding sequences confirmed involvement of proline at 310 in CypA binding. Our findings are consistent with CypA acting on multiple prolines outside of the previously identified CypA binding sites. These results suggest multiple specific genetic variants between genotype 1a and 1b in the C-terminus of NS5A alter the CsA susceptibility of replicons, and some variants may oppose the effects of others.

  18. Mutational Analysis of the Hypervariable Region of Hepatitis E Virus Reveals Its Involvement in the Efficiency of Viral RNA Replication ▿

    Science.gov (United States)

    Pudupakam, R. S.; Kenney, Scott P.; Córdoba, Laura; Huang, Yao-Wei; Dryman, Barbara A.; LeRoith, Tanya; Pierson, F. William; Meng, Xiang-Jin

    2011-01-01

    The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication levels of the HVR deletion mutants were markedly reduced in Huh7 cells, suggesting a role of the HVR in viral replication efficiency. To further verify the results, we constructed HVR deletion mutants by using a genetically divergent, nonmammalian avian HEV, and similar effects on viral replication efficiency were observed when the avian HEV mutants were tested in LMH cells. Furthermore, the impact of complete HVR deletion on virus infectivity was tested in chickens, using an avian HEV mutant with a complete HVR deletion. Although the deletion mutant was still replication competent in LMH cells, the complete HVR deletion resulted in a loss of avian HEV infectivity in chickens. Since the HVR exhibits extensive variations in sequence and length among different HEV genotypes, we further examined the interchangeability of HVRs and demonstrated that HVR sequences are functionally exchangeable between HEV genotypes with regard to viral replication and infectivity in vitro, although genotype-specific HVR differences in replication efficiency were observed. The results showed that although the HVR tolerates small deletions with regard to infectivity, it may interact with viral and host factors to modulate the efficiency of HEV replication. PMID:21775444

  19. Two-Year Assessment of Entecavir Resistance in Lamivudine-Refractory Hepatitis B Virus Patients Reveals Different Clinical Outcomes Depending on the Resistance Substitutions Present▿

    Science.gov (United States)

    Tenney, Daniel J.; Rose, Ronald E.; Baldick, Carl J.; Levine, Steven M.; Pokornowski, Kevin A.; Walsh, Ann W.; Fang, Jie; Yu, Cheng-Fang; Zhang, Sharon; Mazzucco, Charles E.; Eggers, Betsy; Hsu, Mayla; Plym, Mary Jane; Poundstone, Patricia; Yang, Joanna; Colonno, Richard J.

    2007-01-01

    Entecavir (ETV) is a deoxyguanosine analog approved for use for the treatment of chronic infection with wild-type and lamivudine-resistant (LVDr) hepatitis B virus (HBV). In LVD-refractory patients, 1.0 mg ETV suppressed HBV DNA levels to below the level of detection by PCR (M250. To monitor for resistance, available isolates from 192 ETV-treated patients were sequenced, with phenotyping performed for all isolates with all emerging substitutions, in addition to isolates from all patients experiencing virologic rebounds. The T184, S202, or M250 substitution was found in LVDr HBV at baseline in 6% of patients and emerged in isolates from another 11/187 (6%) and 12/151 (8%) ETV-treated patients by Weeks 48 and 96, respectively. However, use of a more sensitive PCR assay detected many of the emerging changes at baseline, suggesting that they originated during LVD therapy. Only a subset of the changes in ETVr isolates altered their susceptibilities, and virtually all isolates were significantly replication impaired in vitro. Consequently, only 2/187 (1%) patients experienced ETVr rebounds in year 1, with an additional 14/151 (9%) patients experiencing ETVr rebounds in year 2. Isolates from all 16 patients with rebounds were LVDr and harbored the T184 and/or S202 change. Seventeen other novel substitutions emerged during ETV therapy, but none reduced the susceptibility to ETV or resulted in a rebound. In summary, ETV was effective in LVD-refractory patients, with resistant sequences arising from a subset of patients harboring preexisting LVDr/ETVr variants and with approximately half of the patients experiencing a virologic rebound. PMID:17178796

  20. Two-year assessment of entecavir resistance in Lamivudine-refractory hepatitis B virus patients reveals different clinical outcomes depending on the resistance substitutions present.

    Science.gov (United States)

    Tenney, Daniel J; Rose, Ronald E; Baldick, Carl J; Levine, Steven M; Pokornowski, Kevin A; Walsh, Ann W; Fang, Jie; Yu, Cheng-Fang; Zhang, Sharon; Mazzucco, Charles E; Eggers, Betsy; Hsu, Mayla; Plym, Mary Jane; Poundstone, Patricia; Yang, Joanna; Colonno, Richard J

    2007-03-01

    Entecavir (ETV) is a deoxyguanosine analog approved for use for the treatment of chronic infection with wild-type and lamivudine-resistant (LVDr) hepatitis B virus (HBV). In LVD-refractory patients, 1.0 mg ETV suppressed HBV DNA levels to below the level of detection by PCR (M250. To monitor for resistance, available isolates from 192 ETV-treated patients were sequenced, with phenotyping performed for all isolates with all emerging substitutions, in addition to isolates from all patients experiencing virologic rebounds. The T184, S202, or M250 substitution was found in LVDr HBV at baseline in 6% of patients and emerged in isolates from another 11/187 (6%) and 12/151 (8%) ETV-treated patients by Weeks 48 and 96, respectively. However, use of a more sensitive PCR assay detected many of the emerging changes at baseline, suggesting that they originated during LVD therapy. Only a subset of the changes in ETVr isolates altered their susceptibilities, and virtually all isolates were significantly replication impaired in vitro. Consequently, only 2/187 (1%) patients experienced ETVr rebounds in year 1, with an additional 14/151 (9%) patients experiencing ETVr rebounds in year 2. Isolates from all 16 patients with rebounds were LVDr and harbored the T184 and/or S202 change. Seventeen other novel substitutions emerged during ETV therapy, but none reduced the susceptibility to ETV or resulted in a rebound. In summary, ETV was effective in LVD-refractory patients, with resistant sequences arising from a subset of patients harboring preexisting LVDr/ETVr variants and with approximately half of the patients experiencing a virologic rebound.

  1. Metabolite profiles reveal energy failure and impaired beta-oxidation in liver of mice with complex III deficiency due to a BCS1L mutation.

    Directory of Open Access Journals (Sweden)

    Heike Kotarsky

    Full Text Available BACKGROUND & AIMS: Liver is a target organ in many mitochondrial disorders, especially if the complex III assembly factor BCS1L is mutated. To reveal disease mechanism due to such mutations, we have produced a transgenic mouse model with c.232A>G mutation in Bcs1l, the causative mutation for GRACILE syndrome. The homozygous mice develop mitochondrial hepatopathy with steatosis and fibrosis after weaning. Our aim was to assess cellular mechanisms for disease onset and progression using metabolomics. METHODS: With mass spectrometry we analyzed metabolite patterns in liver samples obtained from homozygotes and littermate controls of three ages. As oxidative stress might be a mechanism for mitochondrial hepatopathy, we also assessed H(2O(2 production and expression of antioxidants. RESULTS: Homozygotes had a similar metabolic profile at 14 days of age as controls, with the exception of slightly decreased AMP. At 24 days, when hepatocytes display first histopathological signs, increases in succinate, fumarate and AMP were found associated with impaired glucose turnover and beta-oxidation. At end stage disease after 30 days, these changes were pronounced with decreased carbohydrates, high levels of acylcarnitines and amino acids, and elevated biogenic amines, especially putrescine. Signs of oxidative stress were present in end-stage disease. CONCLUSIONS: The findings suggest an early Krebs cycle defect with increases of its intermediates, which might play a role in disease onset. During disease progression, carbohydrate and fatty acid metabolism deteriorate leading to a starvation-like condition. The mouse model is valuable for further investigations on mechanisms in mitochondrial hepatopathy and for interventions.

  2. Glucose-6-phosphatase deficiency

    Directory of Open Access Journals (Sweden)

    Labrune Philippe

    2011-05-01

    Full Text Available Abstract Glucose-6-phosphatase deficiency (G6P deficiency, or glycogen storage disease type I (GSDI, is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea. Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty, generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency. GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib. Mutations in the genes G6PC (17q21 and SLC37A4 (11q23 respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most

  3. What Are Rare Clotting Factor Deficiencies?

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  4. Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

    Science.gov (United States)

    Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

    2013-01-01

    The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications. Copyright © 2012 Wiley Periodicals, Inc.

  5. CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

    Science.gov (United States)

    Kim, Hyunbae; Zheng, Ze; Walker, Paul D; Kapatos, Gregory; Zhang, Kezhong

    2017-07-15

    Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. Copyright © 2017 American Society for Microbiology.

  6. Hepatic Encephalopathy

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    Full Text Available ... to continue to work to my full capacity? Will I be able to drive? Patient Stories Angie M. Caregiver for Brother Charles DiAngelo Hepatic Encephalopathy Jason Dedmon Alcohol-related Cirrhosis ...

  7. Hepatic Encephalopathy

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    Full Text Available ... your body when your liver isn’t working well, it may affect your brain and cause HE. ... it apparent that the liver is not doing well. These could be the symptoms of Hepatic Encephalopathy ( ...

  8. Hepatic Encephalopathy

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    Full Text Available ... bad. It sends the good things – such as vitamins and nutrients – into your bloodstream for your body ... for Wife Joyce O. Caregiver for Mother Lynette K. Hepatic Encephalopathy Samantha W. Caregiver for Husband Stan ...

  9. Hepatic Encephalopathy

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    Full Text Available ... Get Worse? How is HE Diagnosed? Prior to Treatment Who treats HE? Preparing for your Medical Appointment Hepatic Encephalopathy Treatment Options Treatment Basics Treatment Medications Importance of Adhering ...

  10. Hepatic Encephalopathy

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    Full Text Available ... become familiar with the signs of Hepatic Encephalopathy so you can tell your doctor right away if ... with continuous treatment, HE can usually be controlled. So it’s important to tell your doctor about any ...

  11. Hepatic Encephalopathy

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    Full Text Available ... build-up and painful swelling of the legs (edema) and abdomen (ascites) or hepatic encephalopathy. For more ... build up and painful swelling of the legs (edema) and abdomen (ascites) Bruising and bleeding easily Enlarged ...

  12. Hepatic Encephalopathy

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    Full Text Available ... to Treatment Who treats HE? Preparing for your Medical Appointment Hepatic Encephalopathy Treatment Options Treatment Basics Treatment ... treatment. Being a fully-informed participant in your medical care is an important factor in staying as ...

  13. Hepatic Encephalopathy

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    Full Text Available ... Hepatic Encephalopathy so you can tell your doctor right away if you think you may have it. ... American Liver Foundation © 2018 American Liver Foundation. All rights reserved. Funding for the HE123 - Diagnosis, Treatment and ...

  14. Hepatic Encephalopathy

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    Full Text Available ... important for you and your family to become familiar with the signs of Hepatic Encephalopathy so you ... team evaluates the person’s overall physical and mental health, plan to pay for transplant related medical expenses, ...

  15. Hepatic Encephalopathy

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    Full Text Available ... Symptoms to look for Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is ... questions about HE, one step at a time. Home About Us Ways to Give Contact Us Privacy ...

  16. Hepatic Encephalopathy

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    Full Text Available ... responsible for the daily needs of another person. Caregivers can be a friend, spouse, life partner, parent, sibling or other family member. What is HE? Hepatic Encephalopathy, sometimes referred to as ...

  17. Hepatitis C

    Science.gov (United States)

    ... viral load (the amount of HCV in your blood), imaging tests, and biopsy results. Treatment is especially important for people who are showing signs liver fibrosis or scarring. Medicines used to treat hepatitis C ...

  18. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... that can be corrected . It may also occur as part of a chronic problem from liver disease ... worse over time. Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that ...

  19. Hepatitis A

    Science.gov (United States)

    ... Acute liver failure requires a stay in the hospital for monitoring and treatment. Some people with acute liver failure may need a liver transplant. Prevention The hepatitis A vaccine can prevent infection with the virus. The vaccine is typically given ...

  20. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... OVERVIEW Donate Now Join an Event Volunteer Your Time The Legacy Society Make Gifts of Stock Donate ... problem from liver disease that gets worse over time. Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

  1. Hepatic Encephalopathy

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    Full Text Available ... Patient Advisory Council Media Center Careers How You Can Help OVERVIEW Donate Now Join an Event Volunteer ... Hepatic Encephalopathy is a short-term problem that can be corrected . It may also occur as part ...

  2. Hepatic Encephalopathy

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    Full Text Available ... People ALF Near You Events ALF Blogs Financial Information Policies Advocacy Patient Advisory Council Media Center Careers ... and abdomen (ascites) or hepatic encephalopathy. For more information about cirrhosis of the liver and symptoms, call ...

  3. Hepatic Encephalopathy

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    Full Text Available ... Disease (NAFLD) & Non-alcoholic Steatohepatitis (NASH) Autoimmune Hepatitis Bile duct disease such as Primary Biliary Cirrhosis (PBC) ... spleen (splenomegaly) Stone-like particles in gallbladder and bile duct (gallstones) Liver cancer (hepatocellular carcinoma) Chronic liver ...

  4. Autoimmune Hepatitis

    Science.gov (United States)

    ... hepatitis is the most common form in North America. Type 1 can occur at any age; however, ... eastern time, M-F Follow Us NIH… Turning Discovery Into Health ® Research & Funding Current Funding Opportunities Research ...

  5. Hepatic Encephalopathy

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    Full Text Available ... Hepatic Encephalopathy Treatment Options Treatment Basics Treatment Medications Importance of Adhering to Your Treatment Plan Long-Term Considerations Patient Support Finding Support Services Peer Support Groups Financial Assistance Support for My Loved Ones Resources Find ...

  6. Hepatic Encephalopathy

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    Full Text Available ... Hepatic Encephalopathy so you can tell your doctor right away if you think you may have it. ... Site Map © COPYRIGHT 2017 AMERICAN LIVER FOUNDATION. ALL RIGHTS RESERVED. Your Liver Overview

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  7. Hepatic Encephalopathy

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    Full Text Available ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ... travel through your body until they reach your brain, causing mental and physical symptoms of HE. Hepatic ...

  8. Hepatitis B Foundation

    Science.gov (United States)

    ... worldwide 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working ... of people living with hepatitis B. Learn About Hepatitis B in 11 Other Languages . Resource Video See ...

  9. What Is Hepatitis?

    Science.gov (United States)

    ... Navigation Alt+1 Content Alt+2 What is hepatitis? Online Q&A Reviewed July 2016 Q: What ... Question and answer archives Submit a question World Hepatitis Day Posters: Eliminate hepatitis World Hepatitis Day 2017 ...

  10. Feature Hepatitis: Hepatitis Symptoms, Diagnosis, Treatment & Prevention

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis: Symptoms, Diagnosis, Treatment & Prevention Past Issues / Spring 2009 ... No appetite Fever Headaches Diagnosis To check for hepatitis viruses, your doctor will test your blood. You ...

  11. Lysine Acetylation of CREBH Regulates Fasting-Induced Hepatic Lipid Metabolism

    Science.gov (United States)

    Kim, Hyunbae; Mendez, Roberto; Chen, Xuequn; Fang, Deyu

    2015-01-01

    Cyclic AMP-responsive element-binding protein 3-like 3, hepatocyte specific (CREBH), is a hepatic transcription factor that functions as a key regulator of energy homeostasis. Here, we defined a regulatory CREBH posttranslational modification process, namely, lysine-specific acetylation, and its functional involvement in fasting-induced hepatic lipid metabolism. Fasting induces CREBH acetylation in mouse livers in a time-dependent manner, and this event is critical for CREBH transcriptional activity in regulating hepatic lipid homeostasis. The histone acetyltransferase PCAF-mediated acetylation and the deacetylase sirtuin-1-mediated deacetylation coexist to maintain CREBH acetylation states under fasting conditions. Site-directed mutagenesis and functional analyses revealed that the lysine (K) residue at position 294 (K294) within the bZIP domain of the CREBH protein is the site where fasting-induced acetylation/deacetylation occurs. Introduction of the acetylation-deficient (K294R) or acetylation-mimicking (K294Q) mutation inhibited or enhanced CREBH transcriptional activity, respectively. Importantly, CREBH acetylation at lysine 294 was required for the interaction and synergy between CREBH and peroxisome proliferator-activated receptor α (PPARα) in activating their target genes upon fasting or glucagon stimulation. Introduction of the CREBH lysine 294 mutation in the liver leads to hepatic steatosis and hyperlipidemia in animals under prolonged fasting. In summary, our study reveals a molecular mechanism by which fasting or glucagon stimulation modulates lipid homeostasis through acetylation of CREBH. PMID:26438600

  12. Liver Cancer and Hepatitis B

    Science.gov (United States)

    ... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  13. Hepatitis C: Sex and Sexuality

    Science.gov (United States)

    ... with Hepatitis » Sex and Sexuality: Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... hepatitis C virus through sex. Can you pass hepatitis C to a sex partner? Yes, but it ...

  14. Hepatitis C: Diet and Nutrition

    Science.gov (United States)

    ... with Hepatitis » Daily Living: Diet and Nutrition Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... have high cholesterol and have fatty liver. How hepatitis C affects diet If you have hepatitis, you ...

  15. Hepatitis B & C and HIV

    Science.gov (United States)

    ... Find Services HIV SERVICES LOCATOR Locator Search Search Hepatitis B & C Topics Hepatitis B Hepatitis C Hepatitis ... Infections Sexually Transmitted Diseases Smoking Women's Health Issues Hepatitis B Virus and Hepatitis C Virus Infection People ...

  16. Arginase-1 deficiency.

    Science.gov (United States)

    Sin, Yuan Yan; Baron, Garrett; Schulze, Andreas; Funk, Colin D

    2015-12-01

    Arginase-1 (ARG1) deficiency is a rare autosomal recessive disorder that affects the liver-based urea cycle, leading to impaired ureagenesis. This genetic disorder is caused by 40+ mutations found fairly uniformly spread throughout the ARG1 gene, resulting in partial or complete loss of enzyme function, which catalyzes the hydrolysis of arginine to ornithine and urea. ARG1-deficient patients exhibit hyperargininemia with spastic paraparesis, progressive neurological and intellectual impairment, persistent growth retardation, and infrequent episodes of hyperammonemia, a clinical pattern that differs strikingly from other urea cycle disorders. This review briefly highlights the current understanding of the etiology and pathophysiology of ARG1 deficiency derived from clinical case reports and therapeutic strategies stretching over several decades and reports on several exciting new developments regarding the pathophysiology of the disorder using ARG1 global and inducible knockout mouse models. Gene transfer studies in these mice are revealing potential therapeutic options that can be exploited in the future. However, caution is advised in extrapolating results since the lethal disease phenotype in mice is much more severe than in humans indicating that the mouse models may not precisely recapitulate human disease etiology. Finally, some of the functions and implications of ARG1 in non-urea cycle activities are considered. Lingering questions and future areas to be addressed relating to the clinical manifestations of ARG1 deficiency in liver and brain are also presented. Hopefully, this review will spark invigorated research efforts that lead to treatments with better clinical outcomes.

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  18. Acute hepatic encephalopathy with diffuse cortical lesions

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, S.M.; Spreer, J.; Schumacher, M. [Section of Neuroradiology, Univ. of Freiburg (Germany); Els, T. [Dept. of Neurology, University of Freiburg (Germany)

    2001-07-01

    Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

  19. Acute hepatic encephalopathy with diffuse cortical lesions

    International Nuclear Information System (INIS)

    Arnold, S.M.; Spreer, J.; Schumacher, M.; Els, T.

    2001-01-01

    Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis. (orig.)

  20. Quantitative mass spectrometry of histones H3.2 and H3.3 in Suz12-deficient mouse embryonic stem cells reveals distinct, dynamic post-translational modifications at Lys-27 and Lys-36

    DEFF Research Database (Denmark)

    Jung, Hye Ryung; Pasini, Diego; Helin, Kristian

    2010-01-01

    distinct coexisting modifications. In certain cases, high mass accuracy LTQ-Orbitrap MS/MS allowed precise localization of near isobaric coexisting PTMs such as trimethylation and acetylation within individual peptides. ETD MS/MS facilitated sequencing and annotation of phosphorylated histone peptides....... The combined use of ETD and CID MS/MS increased the total number of identified modified peptides. Comparative quantitative analysis of histones from wild type and Suz12-deficient ESCs using stable isotope labeling with amino acids in cell culture and LC-MS/MS revealed a dramatic reduction of H3K27me2 and H3K27......me3 and an increase of H3K27ac, thereby uncovering an antagonistic methyl/acetyl switch at H3K27. The reduction in H3K27 methylation and increase in H3K27 acetylation was accompanied by H3K36 acetylation and methylation. Estimation of the global isoform percentage of unmodified and modified histone...

  1. Management of chronic hepatitis Band C

    African Journals Online (AJOL)

    disorders must be excluded. Serum copper, urinary copper ... storage diseases and a,-antitrypsin deficiency. ... s absent, the specimen should be sent to a centre of excellence for .... Drug-induced chronic liver disease with emphasis on chronic active hepatitis. ..... interferon represent a difficult management problem. Lower.

  2. [Autoimmune hepatitis].

    Science.gov (United States)

    Färkkilä, Martti

    2013-01-01

    Autoimmune hepatitis is chronic liver disease with two subtypes, type 1 with anti nuclear or smooth muscle antibodies and type 2 with LKM1 or LC1 antibodies, and both with hypergammaglobulinemia and typical histology. Prevalence of AIH is between 10 to 17 per 100000 in Europe. Up to 20-40 % of cases present with acute hepatitis. Budesonide can be used as a first line induction therapy in non-cirrhotic patients, and tiopurines, mercaptopurine or mycophenolic acid as maintenance therapies. Patients not responding to conventional therapy can be treated with ciclosporin, tacrolimus or rituximab or finally with liver transplantation.

  3. Iron deficiency

    DEFF Research Database (Denmark)

    Schou, Morten; Bosselmann, Helle; Gaborit, Freja

    2015-01-01

    BACKGROUND: Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked. OBJECTIVES.......043). CONCLUSION: ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF...

  4. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Biliary Cirrhosis (PBC) and Primary Sclerosing Cholangitis (PSC) Metabolic diseases such as Hemochromatosis, Wilson disease and Alpha- ... FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related Liver Disease Alpha-1 Antitrypsin Deficiency ...

  5. Hepatic Encephalopathy

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    Full Text Available ... Diseases of the Liver Lysosomal Acid Lipase Deficiency Liver Cancer Liver Cysts Non-Alcoholic Fatty Liver Disease Primary ... like particles in gallbladder and bile duct (gallstones) Liver cancer (hepatocellular carcinoma) Chronic liver failure indicates that the ...

  6. Hepatic Encephalopathy

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    Full Text Available ... food, drink and medicine. After your intestines break down things that you eat or drink into their ... FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related Liver Disease Alpha-1 Antitrypsin Deficiency ...

  7. Hepatic Encephalopathy

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    Full Text Available ... Ammonia, which is produced by your body when proteins are digested, is one of the toxins that’s ... as Hemochromatosis, Wilson disease and Alpha-1 antitrypsin deficiency Liver failure is a life-threatening condition that ...

  8. Hepatic Encephalopathy

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    Full Text Available ... another person. Caregivers can be a friend, spouse, life partner, parent, sibling or other family member. What ... Alpha-1 antitrypsin deficiency Liver failure is a life-threatening condition that requires hospitalization. Many people do ...

  9. Hepatic Encephalopathy

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    Full Text Available ... of the Liver Lysosomal Acid Lipase Deficiency Liver Cancer Liver Cysts Non-Alcoholic Fatty Liver Disease Primary ... particles in gallbladder and bile duct (gallstones) Liver cancer (hepatocellular carcinoma) Chronic liver failure indicates that the ...

  10. Hepatic Encephalopathy

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    Full Text Available ... Jaundice In Newborns Diseases of the Liver Lysosomal Acid Lipase Deficiency Liver Cancer Liver Cysts Non-Alcoholic Fatty Liver Disease Primary Biliary Cholangitis Primary Sclerosing Cholangitis ...

  11. Thymidine kinase 2 and alanyl-tRNA synthetase 2 deficiencies cause lethal mitochondrial cardiomyopathy: case reports and review of the literature.

    Science.gov (United States)

    Mazurova, Stella; Magner, Martin; Kucerova-Vidrova, Vendula; Vondrackova, Alzbeta; Stranecky, Viktor; Pristoupilova, Anna; Zamecnik, Josef; Hansikova, Hana; Zeman, Jiri; Tesarova, Marketa; Honzik, Tomas

    2017-07-01

    Cardiomyopathy is a common manifestation in neonates and infants with mitochondrial disorders. In this study, we report two cases manifesting with fatal mitochondrial hypertrophic cardiomyopathy, which include the third known patient with thymidine kinase 2 deficiency and the ninth patient with alanyl-tRNA synthetase 2 deficiency. The girl with thymidine kinase 2 deficiency had hypertrophic cardiomyopathy together with regression of gross motor development at the age of 13 months. Neurological symptoms and cardiac involvement progressed into severe myopathy, psychomotor arrest, and cardiorespiratory failure at the age of 22 months. The imaging methods and autoptic studies proved that she suffered from unique findings of leucoencephalopathy, severe, mainly cerebellar neuronal degeneration, and hepatic steatosis. The girl with alanyl-tRNA synthetase 2 deficiency presented with cardiac failure and underlying hypertrophic cardiomyopathy within 12 hours of life and subsequently died at 9 weeks of age. Muscle biopsy analyses demonstrated respiratory chain complex I and IV deficiencies, and histological evaluation revealed massive mitochondrial accumulation and cytochrome c oxidase-negative fibres in both cases. Exome sequencing in the first case revealed compound heterozygozity for one novel c.209T>C and one previously published c.416C>T mutation in the TK2 gene, whereas in the second case homozygozity for the previously described mutation c.1774C>T in the AARS2 gene was determined. The thymidine kinase 2 mutations resulted in severe mitochondrial DNA depletion (to 12% of controls) in the muscle. We present, for the first time, severe leucoencephalopathy and hepatic steatosis in a patient with thymidine kinase 2 deficiency and the finding of a ragged red fibre-like image in the muscle biopsy in a patient with alanyl-tRNA synthetase 2 deficiency.

  12. Histidine Augments the Suppression of Hepatic Glucose Production by Central Insulin Action

    OpenAIRE

    Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime

    2013-01-01

    Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA le...

  13. Effects of betaine supplementation and choline deficiency on folate deficiency-induced hyperhomocysteinemia in rats.

    Science.gov (United States)

    Liu, Ying; Liu, Yi-qun; Morita, Tatsuya; Sugiyama, Kimio

    2012-01-01

    The effect of betaine status on folate deficiency-induced hyperhomocysteinemia was investigated to determine whether folate deficiency impairs homocysteine removal not only by the methionine synthase (MS) pathway but also by the betaine-homocysteine S-methyltransferase (BHMT) pathway. For this purpose, we investigated the effect of dietary supplementation with betaine at a high level (1%) in rats fed a folate-deprived 10% casein diet (10C) and 20% casein diet (20C). We also investigated the effect of choline deprivation on folate deficiency-induced hyperhomocysteinemia in rats fed 20C. Supplementation of folate-deprived 10C and 20C with 1% betaine significantly suppressed folate deprivation-induced hyperhomocysteinemia, but the extent of suppression was partial or limited, especially in rats fed 10C, the suppression of plasma homocysteine increment being 48.5% in rats fed 10C and 69.7% in rats fed 20C. Although betaine supplementation greatly increased hepatic betaine concentration and BHMT activity, these increases did not fully explain why the effect of betaine supplementation was partial or limited. Folate deprivation markedly increased the hepatic concentration of N,N-dimethylglycine (DMG), a known inhibitor of BHMT, and there was a significant positive correlation between hepatic DMG concentration and plasma homocysteine concentration, suggesting that folate deficiency increases hepatic DMG concentration and thereby depresses BHMT reaction, leading to interference with the effect of betaine supplementation. Choline deprivation did not increase plasma homocysteine concentration in rats fed 20C, but it markedly enhanced plasma homocysteine concentration when rats were fed folate-deprived 20C. This indicates that choline deprivation reinforced folate deprivation-induced hyperhomocysteinemia. Increased hepatic DMG concentration was also associated with such an effect. These results support the concept that folate deficiency impairs homocysteine metabolism not only

  14. Evolution of hepatic steatosis to fibrosis and adenoma formation in liver specific growth hormone receptor knockout (GHRLD mice

    Directory of Open Access Journals (Sweden)

    Yong eFan

    2014-12-01

    Full Text Available Background: Non-alcoholic fatty liver disease (NAFLD is one of the most common forms of chronic liver diseases closely associated with obesity and insulin resistance; deficient growth hormone (GH action in liver has been implicated as a mechanism. Here, we investigated the evolution of NAFLD in aged mice with liver-specific GHR deletion. Methods: We examined glucose tolerance, insulin responsiveness and lipid profiles in aged male mice (44-50 weeks with GHRLD. We performed proteomics analysis, pathway-based Superarray assay, as well as quantitative RT-PCR to gain molecular insight into the mechanism(s of GHR-deficiency mediated NAFLD. In addition, we examined the pathological changes of livers of aged GHRLD male mice. Results: The biochemical profile was consistent with that of the metabolic syndrome: abnormal glucose tolerance, impaired insulin secretion, and hyperlipidemia. RT-qPCR analysis of key markers of inflammation revealed a 3-5 fold increase in TNFα and CCL3, confirming the presence of inflammation. Expression of fibrotic markers (e.g., Col1A2 and Col3A1 was significantly increased, together with a 2-3 fold increase in TGFβ transcripts. Proteomics analyses showed a marked decrease of Mup1 and Selenbp2. In addition, pathway-analysis showed that the expression of cell cycle and growth relevant genes (i.e., Ccnd1, Socs2, Socs3 and Egfr were markedly affected in GHRLD liver. Microscopic analyses (H&E of GHRLD livers revealed the presence of hepatic adenomas of different stages of malignancy. Conclusion: Abrogation of GH-signaling in male liver leads to metabolic syndrome, hepatic steatosis, increased inflammation and fibrosis, and development of hepatic tumor. Since obesity, a common precursor of NAFLD, is a state of deficient GH secretion and action, the GHRLD model could be used to unravel the contribution of compromised hepatic GH-signaling in these pathological processes, and help to identify potential targets for intervention.

  15. Hepatitis E

    Science.gov (United States)

    ... room/fact-sheets/detail/hepatitis-e","@context":"http://schema.org","@type":"Article"}; العربية 中文 français русский español ... E: recognition, investigation and control”. The manual gives information about the epidemiology, clinical manifestations of the disease, ...

  16. Hepatic haemangioma

    African Journals Online (AJOL)

    Hp 630 Dual Core

    successful usage of transhepatic compression sutures using polytetrafluoroethylene (PTFE) pledgets and selective ligation of large feeding vessels from right hepatic artery. Surgical resection may not be technically safe or possible in certain cases due to the massive or diffuse nature of the lesion, proximity to vascular ...

  17. Hepatitis B

    Science.gov (United States)

    ... which can lower your chances of developing serious health problems. Your doctor may recommend screening for hepatitis B if you ... see a doctor who specializes in liver diseases. Doctors can treat the health problems related to cirrhosis with medicines, surgery, and other ...

  18. Radiogenic hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Rey, G; Woellgens, P; Haase, W [Katharinenhospital, Stuttgart (F.R. Germany). Strahlenklinik

    1976-08-01

    The article is about a patient who developed hepatitis after post-operative radiotherapy of a hypernephroma on the right side with /sup 60/Co ..gamma.. radiation. The scintigraph showed a normal-sized liver with parenchymal defects. Therapy consisted of anti-emetics and vitamin preparations.

  19. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... of brain function in people with advanced liver disease. When your liver is damaged it can no longer remove toxic substances from your blood. These toxins build up and can travel through your body until they reach your brain, causing mental and physical symptoms of HE. Hepatic Encephalopathy often ...

  20. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... damages your liver over many years – such as long-term alcohol abuse or chronic hepatitis – can cause ... treated. It’s important to continue treatment for as long as necessary to keep HE from coming back. ...

  1. Strategies to rescue the consequences of inducible arginase-1 deficiency in mice.

    Directory of Open Access Journals (Sweden)

    Laurel L Ballantyne

    Full Text Available Arginase-1 catalyzes the conversion of arginine to ornithine and urea, which is the final step of the urea cycle used to remove excess ammonia from the body. Arginase-1 deficiency leads to hyperargininemia in mice and man with severe lethal consequences in the former and progressive neurological impairment to varying degrees in the latter. In a tamoxifen-induced arginase-1 deficient mouse model, mice succumb to the enzyme deficiency within 2 weeks after inducing the knockout and retain <2 % enzyme in the liver. Standard clinical care regimens for arginase-1 deficiency (low-protein diet, the nitrogen-scavenging drug sodium phenylbutyrate, ornithine supplementation either failed to extend lifespan (ornithine or only minimally prolonged lifespan (maximum 8 days with low-protein diet and drug. A conditional, tamoxifen-inducible arginase-1 transgenic mouse strain expressing the enzyme from the Rosa26 locus modestly extended lifespan of neonatal mice, but not that of 4-week old mice, when crossed to the inducible arginase-1 knockout mouse strain. Delivery of an arginase-1/enhanced green fluorescent fusion construct by adeno-associated viral delivery (rh10 serotype with a strong cytomegalovirus-chicken β-actin hybrid promoter rescued about 30% of male mice with lifespan prolongation to at least 6 months, extensive hepatic expression and restoration of significant enzyme activity in liver. In contrast, a vector of the AAV8 serotype driven by the thyroxine-binding globulin promoter led to weaker liver expression and did not rescue arginase-1 deficient mice to any great extent. Since the induced arginase-1 deficient mouse model displays a much more severe phenotype when compared to human arginase-1 deficiency, these studies reveal that it may be feasible with gene therapy strategies to correct the various manifestations of the disorder and they provide optimism for future clinical studies.

  2. Hepatic amebiasis

    Directory of Open Access Journals (Sweden)

    Salles José Maria

    2003-01-01

    Full Text Available Amebiasis can be considered the most aggressive disease of the human intestine, responsible in its invasive form for clinical syndromes, ranging from the classic dysentery of acute colitis to extra-intestinal disease, with emphasis on hepatic amebiasis, unsuitably named amebic liver abscess. Found worldwide, with a high incidence in India, tropical regions of Africa, Mexico and other areas of Central America, it has been frequently reported in Amazonia. The trophozoite reaches the liver through the portal system, provoking enzymatic focal necrosis of hepatocytes and multiple micro-abscesses that coalesce to develop a single lesion whose central cavity contains a homogeneous thick liquid, with typically reddish brown and yellow color similar to "anchovy paste". Right upper quadrant pain, fever and hepatomegaly are the predominant symptoms of hepatic amebiasis. Jaundice is reported in cases with multiple lesions or a very large abscess, and it affects the prognosis adversely. Besides chest radiography, ultrasonography and computerized tomography have brought remarkable contributions to the diagnosis of hepatic abscesses. The conclusive diagnosis is made however by the finding of Entamoeba histolytica trophozoites in the pus and by the detection of serum antibodies to the amoeba. During the evolution of hepatic amebiasis, in spite of the availability of highly effective drugs, some important complications may occur with regularity and are a result of local perforation with extension into the pleural and pericardium cavities, causing pulmonary abscesses and purulent pericarditis, respectively The ruptures into the abdominal cavity may lead to subphrenic abscesses and peritonitis. The treatment of hepatic amebiasis is made by medical therapy, with metronidazole as the initial drug, followed by a luminal amebicide. In patients with large abscesses, showing signs of imminent rupture, and especially those who do not respond to medical treatment, a

  3. Hepatic amebiasis

    Directory of Open Access Journals (Sweden)

    José Maria Salles

    Full Text Available Amebiasis can be considered the most aggressive disease of the human intestine, responsible in its invasive form for clinical syndromes, ranging from the classic dysentery of acute colitis to extra-intestinal disease, with emphasis on hepatic amebiasis, unsuitably named amebic liver abscess. Found worldwide, with a high incidence in India, tropical regions of Africa, Mexico and other areas of Central America, it has been frequently reported in Amazonia. The trophozoite reaches the liver through the portal system, provoking enzymatic focal necrosis of hepatocytes and multiple micro-abscesses that coalesce to develop a single lesion whose central cavity contains a homogeneous thick liquid, with typically reddish brown and yellow color similar to "anchovy paste". Right upper quadrant pain, fever and hepatomegaly are the predominant symptoms of hepatic amebiasis. Jaundice is reported in cases with multiple lesions or a very large abscess, and it affects the prognosis adversely. Besides chest radiography, ultrasonography and computerized tomography have brought remarkable contributions to the diagnosis of hepatic abscesses. The conclusive diagnosis is made however by the finding of Entamoeba histolytica trophozoites in the pus and by the detection of serum antibodies to the amoeba. During the evolution of hepatic amebiasis, in spite of the availability of highly effective drugs, some important complications may occur with regularity and are a result of local perforation with extension into the pleural and pericardium cavities, causing pulmonary abscesses and purulent pericarditis, respectively The ruptures into the abdominal cavity may lead to subphrenic abscesses and peritonitis. The treatment of hepatic amebiasis is made by medical therapy, with metronidazole as the initial drug, followed by a luminal amebicide. In patients with large abscesses, showing signs of imminent rupture, and especially those who do not respond to medical treatment, a

  4. Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E-/- Mice.

    Science.gov (United States)

    Rinne, Petteri; Kadiri, James J; Velasco-Delgado, Mauricio; Nuutinen, Salla; Viitala, Miro; Hollmén, Maija; Rami, Martina; Savontaus, Eriika; Steffens, Sabine

    2018-02-01

    The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis. Apoe -/- (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r e/e ) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe -/- Mc1r e/e mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe -/- controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced Abca1 and Abcg1 expression in the aorta. Furthermore, Apoe -/- Mc1r e/e mice showed a defect in bile acid metabolism that aggravated high-fat diet-induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C high monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6C high monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1. The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation. © 2017 The Authors.

  5. Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity.

    Science.gov (United States)

    Ozcan, Lale; Wong, Catherine C L; Li, Gang; Xu, Tao; Pajvani, Utpal; Park, Sung Kyu Robin; Wronska, Anetta; Chen, Bi-Xing; Marks, Andrew R; Fukamizu, Akiyoshi; Backs, Johannes; Singer, Harold A; Yates, John R; Accili, Domenico; Tabas, Ira

    2012-05-02

    Hepatic glucose production (HGP) is crucial for glucose homeostasis, but the underlying mechanisms have not been fully elucidated. Here, we show that a calcium-sensing enzyme, CaMKII, is activated in a calcium- and IP3R-dependent manner by cAMP and glucagon in primary hepatocytes and by glucagon and fasting in vivo. Genetic deficiency or inhibition of CaMKII blocks nuclear translocation of FoxO1 by affecting its phosphorylation, impairs fasting- and glucagon/cAMP-induced glycogenolysis and gluconeogenesis, and lowers blood glucose levels, while constitutively active CaMKII has the opposite effects. Importantly, the suppressive effect of CaMKII deficiency on glucose metabolism is abrogated by transduction with constitutively nuclear FoxO1, indicating that the effect of CaMKII deficiency requires nuclear exclusion of FoxO1. This same pathway is also involved in excessive HGP in the setting of obesity. These results reveal a calcium-mediated signaling pathway involved in FoxO1 nuclear localization and hepatic glucose homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Counter-attack on viral hepatitis. [Hepatitis A; Hepatitis B

    Energy Technology Data Exchange (ETDEWEB)

    Prozesky, O W [Pretoria Univ. (South Africa). Dept. of Medical Virology; Jupp, P G; Joubert, J J; Taylor, M B; Grabow, W O.K.

    1985-07-01

    The most highly developed radioimmunoassay test system in medical virology is proving of exceptional value in research aimed at controlling and eventually eradicating the scourge of human hepatitis. The use of radioimmunoassay in detecting hepatitis A (HAV) and hepatitis B (HBV) viruses is discussed. The hepatitis A virus is an enterovirus which infects the gastrointestinal tract and is usually transmitted by contaminated food, milk or water. Hepatitis B spreads mainly by the parenteral rate. Bedbugs and ticks are considered as possible transmitters of HBV. Another important contribution of radioimmunoassay is the ability to monitor the immune response of persons at risk who are vaccinated against hepatitis B.

  7. ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)

    Science.gov (United States)

    2018-05-21

    Acute Hepatic Porphyria; Acute Intermittent Porphyria; Porphyria, Acute Intermittent; Acute Porphyria; Hereditary Coproporphyria (HCP); Variegate Porphyria (VP); ALA Dehydratase Deficient Porphyria (ADP)

  8. Induction of monooxygenases and incorporation of radioactivity from 2-14C-lysine into hepatic microsomes of phenobarbital-treated rats fed a diet deficient in lysine, methionine, threonine and vitamines A, C, E

    International Nuclear Information System (INIS)

    Nurmagambetov, T.Zh.; Amirov, B.B.; Kuanysheva, T.G.; Sharmanov, T.Sh.

    1992-01-01

    The effect of diet on induction of monooxygenases and distribution of radioactivity from 2- 14 C-lysine in fractions of liver homogenate, muscle homogenate and blood of male rats treated with phenobarbital was studied. 2- 14 C-lysin was injected intraperitoneally 24 h before the first injection of phenobarbital. It was demonstrated that monooxygenase induction, increase of relative liver weight and incorporation of radioactivity from 2- 14 C-lysine into fractions of liver homogenate in phenobarbital-treated rats fed diet deficient in lysine, methionine, threonine and vitamins A, C, E were more pronounced as compared with the similarly treated rats which were fed a balanced diet. The possibility of mobilization of deficient essencial components to liver from other organs and tissues for maintenance of monooxygenase induction iis discussed

  9. Congenital Hepatic Cyst

    Directory of Open Access Journals (Sweden)

    Aldo Recinos

    2017-04-01

    Full Text Available Congenital hepatic cyst is a rare and nonsymptomatic condition in infants and children. Its incidence is 2.5% in the postnatal life with a much lower incidence in the prenatal period. Incidental finding on antenatal imaging is the most common presentation. We present a case of a newborn in whom fetal ultrasound detected a cyst within the fetal liver. Postnatal imaging revealed a liver cyst in the right lobe of the liver, with no other intrahepatic structure affected. Liver function tests were abnormal, but the patient was asymptomatic. Posterior follow-up imaging showed a minor decrease in size. Management of congenital hepatic cyst is usually conservative, done with periodic ultrasound monitoring. However, surgical treatment is the mainstay of treatment when hydrops, progressive enlargement, hemorrhage, torsion, or compression of adjacent structures occurs. Malignant transformation can occur, but it is extremely rare. Partial or total removal of the cyst is the preferred treatment in neonates with a large lesion.

  10. Hepatic lipidosis in turkeys.

    Science.gov (United States)

    Gazdzinski, P; Squires, E J; Julian, R J

    1994-01-01

    Two flocks of 14,000 twenty-week-old turkey hens each experienced increased mortality due to hepatic lipidosis. Some hens showed signs of dyspnea and cyanosis before death. Necropsy revealed dark muscles and enlarged livers with pale areas and numerous hemorrhages. Petechial and ecchymotic hemorrhages were also found on the abdominal fat and epicardium. Lung congestion and edema were prominent. In the heart and blood vessels, the blood was uncoagulated. Mortality was elevated for 12 days and resulted in the death of 0.7% of the turkey hens in one flock and 1.7% in the other. Vitamin E administered in water at a dose of 25 IU per hen appeared to reduce mortality. The nutritional and environmental factors that may contribute to the development of hepatic lipidosis in turkeys are discussed.

  11. Hepatitis B (HBV)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hepatitis B KidsHealth / For Teens / Hepatitis B What's in ... Prevented? Print en español Hepatitis B What Is Hepatitis B? Hepatitis B is an infection of the ...

  12. Hepatitis A Vaccine

    Science.gov (United States)

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... Why get vaccinated against hepatitis A?Hepatitis A is a serious liver disease. It is caused by the hepatitis A virus (HAV). HAV is spread from ...

  13. Mechanism of the Dual Activities of Human CYP17A1 and Binding to Anti-Prostate Cancer Drug Abiraterone Revealed by a Novel V366M Mutation Causing 17,20 Lyase Deficiency

    Directory of Open Access Journals (Sweden)

    Mónica Fernández-Cancio

    2018-04-01

    Full Text Available The CYP17A1 gene regulates sex steroid biosynthesis in humans through 17α-hydroxylase/17,20 lyase activities and is a target of anti-prostate cancer drug abiraterone. In a 46, XY patient with female external genitalia, together with a loss of function mutation S441P, we identified a novel missense mutation V366M at the catalytic center of CYP17A1 which preferentially impaired 17,20 lyase activity. Kinetic experiments with bacterially expressed proteins revealed that V366M mutant enzyme can bind and metabolize pregnenolone to 17OH-pregnenolone, but 17OH-pregnenolone binding and conversion to dehydroepiandrosterone (DHEA was impaired, explaining the patient’s steroid profile. Abiraterone could not bind and inhibit the 17α-hydroxylase activity of the CYP17A1-V366M mutant. Molecular dynamics (MD simulations showed that V366M creates a “one-way valve” and suggests a mechanism for dual activities of human CYP17A1 where, after the conversion of pregnenolone to 17OH-pregnenolone, the product exits the active site and re-enters for conversion to dehydroepiandrosterone. The V366M mutant also explained the effectiveness of the anti-prostate cancer drug abiraterone as a potent inhibitor of CYP17A1 by binding tightly at the active site in the WT enzyme. The V366M is the first human mutation to be described at the active site of CYP17A1 that causes isolated 17,20 lyase deficiency. Knowledge about the specificity of CYP17A1 activities is of importance for the development of treatments for polycystic ovary syndrome and inhibitors for prostate cancer therapy.

  14. Lipidomics and H218O labeling techniques reveal increased remodeling of DHA-containing membrane phospholipids associated with abnormal locomotor responses in α-tocopherol deficient zebrafish (danio rerio embryos

    Directory of Open Access Journals (Sweden)

    Melissa Q. McDougall

    2016-08-01

    Full Text Available We hypothesized that vitamin E (α-tocopherol is required by the developing embryonic brain to prevent depletion of highly polyunsaturated fatty acids, especially docosahexaenoic acid (DHA, 22:6, the loss of which we predicted would underlie abnormal morphological and behavioral outcomes. Therefore, we fed adult 5D zebrafish (Danio rerio defined diets without (E− or with added α-tocopherol (E+, 500 mg RRR-α-tocopheryl acetate/kg diet for a minimum of 80 days, and then spawned them to obtain E− and E+ embryos. The E− compared with E+ embryos were 82% less responsive (p<0.01 to a light/dark stimulus at 96 h post-fertilization (hpf, demonstrating impaired locomotor behavior, even in the absence of gross morphological defects. Evaluation of phospholipid (PL and lysophospholipid (lyso-PL composition using untargeted lipidomics in E− compared with E+ embryos at 24, 48, 72, and 120 hpf showed that four PLs and three lyso-PLs containing docosahexaenoic acid (DHA, including lysophosphatidylcholine (LPC 22:6, required for transport of DHA into the brain, p<0.001, were at lower concentrations in E− at all time-points. Additionally, H218O labeling experiments revealed enhanced turnover of LPC 22:6 (p<0.001 and three other DHA-containing PLs in the E− compared with the E+ embryos, suggesting that increased membrane remodeling is a result of PL depletion. Together, these data indicate that α-tocopherol deficiency in the zebrafish embryo causes the specific depletion and increased turnover of DHA-containing PL and lyso-PLs, which may compromise DHA delivery to the brain and thereby contribute to the functional impairments observed in E− embryos.

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  16. Iron-Deficiency Anemia

    Science.gov (United States)

    ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  17. /sup 131/I-Bromsulphalein in the evaluation of hepatic function during reconvalescence after viral hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Chernysheva, N N; Pal' tseva, T F; Nonikova, T B; Aleshkovich, T V; Kuandykova, S Zh; Rumyantseva, L A; Kal' nitskaya, E F [Tsentral' nyj Inst. Usovershenstvovaniya Vrachej, Moscow (USSR)

    1982-10-01

    The combined use of biochemical and radionuclide tests (the clearance of /sup 131/I-bromsulphalein) made it possible to reveal significant differences in 53 patients in the time of complete reparation of hepatic function and the period of reconvalescence after hepatitis A and B. The period of reconvalescence in patients with hepatitis B was more prolonged. Dynamic observation and appropriate treatment is recommended for these patients.

  18. Fulminant hepatic failure in children: Etiology, histopathology and MDCT findings

    International Nuclear Information System (INIS)

    Cakir, Banu; Kirbas, Ismail; Demirhan, Beyhan; Tarhan, Nefise Cagla; Bozkurt, Alper; Ozcay, Figen; Coskun, Mehmet

    2009-01-01

    Introduction: The purpose of this study is to determine the etiologies, histopathology and MDCT findings of children with fulminant hepatic failure admitted to our institution. Materials and methods: Between June 2004 and November 2006, 15 children with fulminant hepatic failure who underwent MDCT were included retrospectively in this study. Twelve patients had liver biopsies. The patients were divided into three groups as hyperacute (Group I), acute (Group II) and subacute (Group III) depending on onset of hepatic encephalopathy. Results: Hepatitis A in 4 patients, non-A, non-E hepatitis in 4; mushroom poisoning in 3; fulminant Wilson's disease in 2; autoimmune hepatitis in 1; and both hepatitis B and toxic hepatitis (with leflunomide treatment) in 1 patient were detected. MDCT of all three groups revealed diffuse reduction in hepatic attenuation in 11 patients; ascites in 9; periportal edema in 6; edema of gallbladder wall in 6; splenomegaly in 6; heterogeneous hepatic parenchyma in 6; hepatomegaly in 3; irregular contours of liver in 2; multiple micronodules in 1 and necrotic areas and regeneration in liver parenchyma in 2 patients. Histopathologic evaluation of liver biopsies showed massive hepatic necrosis, inflammatory cell infiltration and ductular proliferation in 8 patients, periportal edema in 6, edema of gallbladder wall in 5, regenerating nodules and fibrous septa consistent with cirrhotic pattern in 2, and regenerating nodules and necrotic areas in 2 patients. Conclusion: The most common MDCT findings in fulminant hepatic failure were diffuse reduction in hepatic attenuation and ascites. Massive hepatic necrosis was the most common histopathologic finding.

  19. Hepatic (Liver) Function Panel

    Science.gov (United States)

    ... Educators Search English Español Blood Test: Hepatic (Liver) Function Panel KidsHealth / For Parents / Blood Test: Hepatic (Liver) ... kidneys ) is working. What Is a Hepatic (Liver) Function Panel? A liver function panel is a blood ...

  20. Hepatitis C and Incarceration

    Science.gov (United States)

    ... Hepatitis Cdo to take care of their liver? People with Hepatitis C should not use alcohol or street drugs, as these can hurt the liver. Some other products can also hurt people with Hepatitis C, even if they appear to ...

  1. Hepatitis B virus (image)

    Science.gov (United States)

    Hepatitis B is also known as serum hepatitis and is spread through blood and sexual contact. It is ... population. This photograph is an electronmicroscopic image of hepatitis B virus particles. (Image courtesy of the Centers for ...

  2. Hepatitis Risk Assessment

    Science.gov (United States)

    ... please visit this page: About CDC.gov . Hepatitis Risk Assessment Recommend on Facebook Tweet Share Compartir Viral Hepatitis. Are you at risk? Take this 5 minute Hepatitis Risk Assessment developed ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron- ... iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... to moderate iron-deficiency anemia, or red blood cell transfusion for severe iron-deficiency anemia. You may ... body needs iron to make healthy red blood cells. Iron-deficiency anemia usually develops over time because ...

  5. Vitamin Deficiency Anemia

    Science.gov (United States)

    ... are unique to specific vitamin deficiencies. Folate-deficiency anemia risk factors include: Undergoing hemodialysis for kidney failure. ... the metabolism of folate. Vitamin B-12 deficiency anemia risk factors include: Lack of intrinsic factor. Most ...

  6. Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine.

    Science.gov (United States)

    Ikram, Aqsa; Obaid, Ayesha; Awan, Faryal Mehwish; Hanif, Rumeza; Naz, Anam; Paracha, Rehan Zafar; Ali, Amjad; Janjua, Hussnain Ahmed

    2017-01-01

    Cellular immune responses (T cell responses) during hepatitis C virus (HCV) infection are significant factors for determining the outcome of infection. HCV adapts to host immune responses by inducing mutations in its genome at specific sites that are important for HLA processing/presentation. Moreover, HCV also adapts to resist potential drugs that are used to restrict its replication, such as direct-acting antivirals (DAAs). Although DAAs have significantly reduced disease burden, resistance to these drugs is still a challenge for the treatment of HCV infection. Recently, drug resistance mutations (DRMs) observed in HCV proteins (NS3/4A, NS5A and NS5B) have heightened concern that the emergence of drug resistance may compromise the effectiveness of DAAs. Therefore, the NS3/4A, NS5A and NS5B drug resistance variations were investigated in this study, and their prevalence was examined in a large number of protein sequences from all HCV genotypes. Furthermore, potential CD4 + and CD8 + T cell epitopes were predicted and their overlap with genetic variations was explored. The findings revealed that many reported DRMs within NS3/4A, NS5A and NS5B are not drug-induced; rather, they are already present in HCV strains, as they were also detected in HCV-naïve patients. This study highlights several hot spots in which HLA and drug selective pressure overlap. Interestingly, these overlapping mutations were frequently observed among many HCV genotypes. This study implicates that knowledge of the host HLA type and HCV subtype/genotype can provide important information in defining personalized therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Hepatitis B Vaccine

    Science.gov (United States)

    ... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  8. Expression profiling analysis: Uncoupling protein 2 deficiency improves hepatic glucose, lipid profiles and insulin sensitivity in high-fat diet-fed mice by modulating expression of genes in peroxisome proliferator-activated receptor signaling pathway.

    Science.gov (United States)

    Zhou, Mei-Cen; Yu, Ping; Sun, Qi; Li, Yu-Xiu

    2016-03-01

    Uncoupling protein 2 (UCP2), which was an important mitochondrial inner membrane protein associated with glucose and lipid metabolism, widely expresses in all kinds of tissues including hepatocytes. The present study aimed to explore the impact of UCP2 deficiency on glucose and lipid metabolism, insulin sensitivity and its effect on the liver-associated signaling pathway by expression profiling analysis. Four-week-old male UCP2-/- mice and UCP2+/+ mice were randomly assigned to four groups: UCP2-/- on a high-fat diet, UCP2-/- on a normal chow diet, UCP2+/+ on a high-fat diet and UCP2+/+ on a normal chow diet. The differentially expressed genes in the four groups on the 16th week were identified by Affymetrix gene array. The results of intraperitoneal glucose tolerance test and insulin tolerance showed that blood glucose and β-cell function were improved in the UCP2-/- group on high-fat diet. Enhanced insulin sensitivity was observed in the UCP2-/- group. The differentially expressed genes were mapped to 23 pathways (P high-fat diet. The upregulation of genes in the PPAR signaling pathway could explain our finding that UCP2 deficiency ameliorated insulin sensitivity. The manipulation of UCP2 protein expression could represent a new strategy for the prevention and treatment of diabetes.

  9. Hepatitis C virus core protein induces hepatic steatosis via Sirt1-dependent pathway.

    Science.gov (United States)

    Zhang, Chuanhai; Wang, Jingjing; Zhang, Hanlin; Liu, Shunai; Lee, Hyuek Jong; Jin, Wanzhu; Cheng, Jun

    2018-05-01

    Hepatic steatosis is a common feature of patients with chronic hepatitis C. Previous reports have shown that the overexpression of hepatitis C virus core-encoding sequences (hepatitis C virus genotypes 3a and 1b) significantly induces intracellular triglyceride accumulation. However, the underlying mechanism has not yet been revealed. To investigate whether Sirt1 is involved in hepatitis C virus-mediated hepatic steatosis, the overexpression of hepatitis C virus core 1b protein and Sirt1 and the knockdown of Sirt1 in HepG2 cells were performed. To confirm the results of the cellular experiment liver-specific Sirt1 KO mice with lentivirus-mediated hepatitis C virus core 1b overexpression were studied. Our results show that hepatitis C virus core 1b protein overexpression led to the accumulation of triglycerides in HepG2 cells. Notably the expression of PPARγ2 was dramatically increased at both the mRNA and protein levels by hepatitis C virus core 1b overexpression. The protein expression of Sirt1 is an upstream regulator of PPARγ2 and was also significantly increased after core 1b overexpression. In addition, the overexpression or knockdown of Sirt1 expression alone was sufficient to modulate p300-mediated PPARγ2 deacetylation. In vivo studies showed that hepatitis C virus core protein 1b-induced hepatic steatosis was attenuated in liver-specific Sirt1 KO mice by downregulation of PPARγ2 expression. Sirt1 mediates hepatitis C virus core protein 1b-induced hepatic steatosis by regulation of PPARγ2 expression. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Expression of scavenger receptor‐AI promotes alternative activation of murine macrophages to limit hepatic inflammation and fibrosis

    Science.gov (United States)

    Labonte, Adam C.; Sung, Sun‐Sang J.; Jennelle, Lucas T.; Dandekar, Aditya P.

    2016-01-01

    The liver maintains an immunologically tolerant environment as a result of continuous exposure to food and bacterial constituents from the digestive tract. Hepatotropic pathogens can take advantage of this niche and establish lifelong chronic infections causing hepatic fibrosis and hepatocellular carcinoma. Macrophages (Mϕ) play a critical role in regulation of immune responses to hepatic infection and regeneration of tissue. However, the factors crucial for Mϕ in limiting hepatic inflammation or resolving liver damage have not been fully understood. In this report, we demonstrate that expression of C‐type lectin receptor scavenger receptor‐AI (SR‐AI) is crucial for promoting M2‐like Mϕ activation and polarization during hepatic inflammation. Liver Mϕ uniquely up‐regulated SR‐AI during hepatotropic viral infection and displayed increased expression of alternative Mϕ activation markers, such as YM‐1, arginase‐1, and interleukin‐10 by activation of mer receptor tyrosine kinase associated with inhibition of mammalian target of rapamycin. Expression of these molecules was reduced on Mϕ obtained from livers of infected mice deficient for the gene encoding SR‐AI (msr1). Furthermore, in vitro studies using an SR‐AI‐deficient Mϕ cell line revealed impeded M2 polarization and decreased phagocytic capacity. Direct stimulation with virus was sufficient to activate M2 gene expression in the wild‐type (WT) cell line, but not in the knockdown cell line. Importantly, tissue damage and fibrosis were exacerbated in SR‐AI–/– mice following hepatic infection and adoptive transfer of WT bone‐marrow–derived Mϕ conferred protection against fibrosis in these mice. Conclusion: SR‐AI expression on liver Mϕ promotes recovery from infection‐induced tissue damage by mediating a switch to a proresolving Mϕ polarization state. (Hepatology 2017;65:32‐43). PMID:27770558

  11. Atypical B12 Deficiency with Nonresolving Paraesthesia

    Directory of Open Access Journals (Sweden)

    S. Haider

    2013-01-01

    Full Text Available Vitamin B12 deficiency can present with various hematological, gastrointestinal and neurological manifestations. We report a case of elderly female who presented with neuropathy and vitamin B12 deficiency where the final work-up revealed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS. This case suggests that, although POEMS syndrome is a rare entity, it can present with vitamin-B12 deficiency and thus specific work up for early diagnosis of POEMS should be considered in patients with B12 deficiency unresponsive to therapy.

  12. Induction of monooxygenases and incorporation of radioactivity from 2-14C-lysine into hepatic microsomes of phenobarbital-treated rats fed a diet deficient in lysine, methionine, threonine and vitamine A, C and E

    International Nuclear Information System (INIS)

    Nurmagambetov, T.Zh.; Amirov, B.B.; Kuanysheva, T.K.; Sharmanov, T.Sh.

    1991-01-01

    The effect of diet on induction of monooxygenases and distribution of label from 2- 14 C-lysine in fractions of liver homogenate, muscle homogenate and blood of male rats treated with phenobarbital (80 mg/rg, three days) was studied. 2- 14 C-lysine was injected intraperitoneally 24 h before the first injection of phenobarbital. It was demonstrated that monooxygenase induction, increase of relative liver weight and incorporation of label from 2- 14 C-lysine into fractions of liver homogenate in phenobarbital-treated rats were more pronounced as compared with the similarly trated rats that were fed a balanced diet. The possibility of mobilization of deficient essential components to liver from other organs and tissues for maintenance of monooxygenase induction is discussed

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency anemia is a ... address the cause of your iron deficiency, such as any underlying bleeding. If undiagnosed or untreated, iron- ...

  14. Diagnostic value of liver scintigraphy, computed tomography and ultrasonography of fatal hepatitis

    International Nuclear Information System (INIS)

    Komori, Hideshi; Hirasa, Masahiro; Ibuki, Yasuyoshi

    1983-01-01

    The purpose of this study was investigate the diagnostic value of liver scintigraphy, computed tomography (CT) and ultrasonography in acute hepatic failure, subacute hepatitis and acute hepatitis. By scintigraphy low uptake in the liver and high uptake in the spleen and bone marrow were observed in hepatic failure. However, uneven liver edge and heterogenous RI destribution were not corresponded to massive necrosis. In fulminant hepatitis, liver size and other findings were variable in patient by patient. But in subacute hepatitis, the findings were typical. The finding of left lobe swelling was observed in a half of patients with acute hepatic failure based on chronic hepatitis. Localized low density area by the CT was detected in most of the cases of subacute hepatitis, and acute hepatitis with submassive hepatic necrosis. But in fulminant hepatitis, that was rare. In these cases, irregular and strong lesion was also obsurved by ultrasonography. These findings by the CT and ultrasonography were corresponded to massive necrosis histrogically ultrasonography revealed narrowing of hepatic vein in fatal hepatitis. Localized low density area by the CT in subacute hepatitis was shown surrounding hepatic vein. We conclude that development of massine hepatic necrosis concern to secondary hepatic ischemia. (author)

  15. HIV and Viral Hepatitis

    Science.gov (United States)

    ... common causes of viral hepatitis are hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). HBV and HCV are common ... gov/ mmwr/ preview/ mmwrhtml/ rr5516a1. htm? s_ cid= rr5516a1_ e. The Numbers • • Of people with HIV in the ...

  16. Insulin-Inducible SMILE Inhibits Hepatic Gluconeogenesis.

    Science.gov (United States)

    Lee, Ji-Min; Seo, Woo-Young; Han, Hye-Sook; Oh, Kyoung-Jin; Lee, Yong-Soo; Kim, Don-Kyu; Choi, Seri; Choi, Byeong Hun; Harris, Robert A; Lee, Chul-Ho; Koo, Seung-Hoi; Choi, Hueng-Sik

    2016-01-01

    The role of a glucagon/cAMP-dependent protein kinase-inducible coactivator PGC-1α signaling pathway is well characterized in hepatic gluconeogenesis. However, an opposing protein kinase B (PKB)/Akt-inducible corepressor signaling pathway is unknown. A previous report has demonstrated that small heterodimer partner-interacting leucine zipper protein (SMILE) regulates the nuclear receptors and transcriptional factors that control hepatic gluconeogenesis. Here, we show that hepatic SMILE expression was induced by feeding in normal mice but not in db/db and high-fat diet (HFD)-fed mice. Interestingly, SMILE expression was induced by insulin in mouse primary hepatocyte and liver. Hepatic SMILE expression was not altered by refeeding in liver-specific insulin receptor knockout (LIRKO) or PKB β-deficient (PKBβ(-/-)) mice. At the molecular level, SMILE inhibited hepatocyte nuclear factor 4-mediated transcriptional activity via direct competition with PGC-1α. Moreover, ablation of SMILE augmented gluconeogenesis and increased blood glucose levels in mice. Conversely, overexpression of SMILE reduced hepatic gluconeogenic gene expression and ameliorated hyperglycemia and glucose intolerance in db/db and HFD-fed mice. Therefore, SMILE is an insulin-inducible corepressor that suppresses hepatic gluconeogenesis. Small molecules that enhance SMILE expression would have potential for treating hyperglycemia in diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Functional PAK-2 knockout and replacement with a caspase cleavage-deficient mutant in mice reveals differential requirements of full-length PAK-2 and caspase-activated PAK-2p34.

    Science.gov (United States)

    Marlin, Jerry W; Chang, Yu-Wen E; Ober, Margaret; Handy, Amy; Xu, Wenhao; Jakobi, Rolf

    2011-06-01

    p21-Activated protein kinase 2 (PAK-2) has both anti- and pro-apoptotic functions depending on its mechanism of activation. Activation of full-length PAK-2 by the monomeric GTPases Cdc42 or Rac stimulates cell survival, whereas caspase activation of PAK-2 to the PAK-2p34 fragment is involved in the apoptotic response. In this study we use functional knockout of PAK-2 and gene replacement with the caspase cleavage-deficient PAK-2D212N mutant to differentiate the biological functions of full-length PAK-2 and caspase-activated PAK-2p34. Knockout of PAK-2 results in embryonic lethality at early stages before organ development, whereas replacement with the caspase cleavage-deficient PAK-2D212N results in viable and healthy mice, indicating that early embryonic lethality is caused by deficiency of full-length PAK-2 rather than lack of caspase activation to the PAK-2p34 fragment. However, deficiency of caspase activation of PAK-2 decreased spontaneous cell death of primary mouse embryonic fibroblasts and increased cell growth at high cell density. In contrast, stress-induced cell death by treatment with the anti-cancer drug cisplatin was not reduced by deficiency of caspase activation of PAK-2, but switched from an apoptotic to a nonapoptotic, caspase-independent mechanism. Homozygous PAK-2D212N primary mouse embryonic fibroblasts that lack the ability to generate the proapoptotic PAK-2p34 show less activation of the effector caspase 3, 6, and 7, indicating that caspase activation of PAK-2 amplifies the apoptotic response through a positive feedback loop resulting in more activation of effector caspases.

  18. Deficiency of the Chemotactic Factor Inactivator in Human Sera with α1-Antitrypsin Deficiency

    Science.gov (United States)

    Ward, Peter A.; Talamo, Richard C.

    1973-01-01

    As revealed by appropriate fractionation procedures, human serum deficient in α1-antitrypsin (α1-AT) is also deficient in the naturally occurring chemotactic factor inactivator. These serum donors had severe pulmonary emphysema. Serum from patients with clinically similar pulmonary disease, but with presence of α1-AT in the serum, showed no such deficiency of the chemotactic factor inactivator. When normal human serum and α1-AT-deficient human sera are chemotactically activated by incubation with immune precipitates, substantially more chemotactic activity is generated in α1-AT-deficient serum. These data indicate that in α1-AT-deficient serum there is an imbalance in the generation and control of chemotactic factors. It is suggested that the theory regarding development of pulmonary emphysema in patients lacking the α1-antitrypsin in their serum should be modified to take into account a deficiency of the chemotactic factor inactivator. PMID:4683887

  19. Acquired factor VII deficiency associated with acute myeloid leukemia.

    Science.gov (United States)

    Anoun, Soumaya; Lamchahab, Mouna; Oukkache, Bouchra; Qachouh, Maryam; Benchekroun, Said; Quessar, Asmaa

    2015-04-01

    Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics.

  20. Hepatic radiography

    International Nuclear Information System (INIS)

    Bernardino, M.E.; Sones, P.J.

    1985-01-01

    The past several years have seen significant advances in diagnostic and interventional radiology. These advances have been particularly rewarding for the study of liver disease. Improved imaging and therapeutic procedures in oncology have generated changes in treatment protocols and in evaluating the results of therapy for hepatic malignancies. The enriched understanding of the anatomic and hemodynamic aspects of the portal system has greatly benefited patients with portal hypertension. Now physicians are confidently more aggressive in the therapeutic approach to the variceal bleeder, and they have modified their approach to the preservation of portal flow following shunt. All of the diagnostic modalities used to evaluate the liver are represented in this book. In its structure and organization this volume goes beyond a historical overview of imaging to present greater insight into the current state of the art, as well as possible future developments. Each chapter is designed to elucidate the advantages and weaknesses of the various diagnostic modalities

  1. Bile acids override steatosis in farnesoid X receptor deficient mice in a model of non-alcoholic steatohepatitis

    International Nuclear Information System (INIS)

    Wu, Weibin; Liu, Xijun; Peng, Xiaomin; Xue, Ruyi; Ji, Lingling; Shen, Xizhong; Chen, She; Gu, Jianxin; Zhang, Si

    2014-01-01

    Highlights: • FXR deficiency enhanced MCD diet-induced hepatic fibrosis. • FXR deficiency attenuated MCD diet-induced hepatic steatosis. • FXR deficiency repressed genes involved in fatty acid uptake and triglyceride accumulation. - Abstract: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, and the pathogenesis is still not well known. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily and plays an essential role in maintaining bile acid and lipid homeostasis. In this study, we study the role of FXR in the pathogenesis of NFALD. We found that FXR deficient (FXR −/− ) mice fed methionine- and choline-deficient (MCD) diet had higher serum ALT and AST activities and lower hepatic triglyceride levels than wild-type (WT) mice fed MCD diet. Expression of genes involved in inflammation (VCAM-1) and fibrosis (α-SMA) was increased in FXR −/− mice fed MCD diet (FXR −/− /MCD) compared to WT mice fed MCD diet (WT/MCD). Although MCD diet significantly induced hepatic fibrosis in terms of liver histology, FXR −/− /MCD mice showed less degree of hepatic steatosis than WT/MCD mice. Moreover, FXR deficiency synergistically potentiated the elevation effects of MCD diet on serum and hepatic bile acids levels. The super-physiological concentrations of hepatic bile acids in FXR −/− /MCD mice inhibited the expression of genes involved in fatty acid uptake and triglyceride accumulation, which may be an explanation for less steatosis in FXR −/− /MCD mice in contrast to WT/MCD mice. These results suggest that hepatic bile acids accumulation could override simple steatosis in hepatic injury during the progression of NAFLD and further emphasize the role of FXR in maintaining hepatic bile acid homeostasis in liver disorders and in hepatic protection

  2. Bile acids override steatosis in farnesoid X receptor deficient mice in a model of non-alcoholic steatohepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Weibin; Liu, Xijun; Peng, Xiaomin [Gene Research Center, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Xue, Ruyi [Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai Institute of Liver Disease, Fudan University, Shanghai 200032 (China); Ji, Lingling [Gene Research Center, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Shen, Xizhong [Department of Gastroenterology and Hepatology, Zhongshan Hospital, Shanghai Institute of Liver Disease, Fudan University, Shanghai 200032 (China); Chen, She, E-mail: shechen@fudan.edu.cn [Gene Research Center, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Gene Research Center, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhang, Si, E-mail: zhangsi@fudan.edu.cn [Gene Research Center, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China)

    2014-05-23

    Highlights: • FXR deficiency enhanced MCD diet-induced hepatic fibrosis. • FXR deficiency attenuated MCD diet-induced hepatic steatosis. • FXR deficiency repressed genes involved in fatty acid uptake and triglyceride accumulation. - Abstract: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, and the pathogenesis is still not well known. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily and plays an essential role in maintaining bile acid and lipid homeostasis. In this study, we study the role of FXR in the pathogenesis of NFALD. We found that FXR deficient (FXR{sup −/−}) mice fed methionine- and choline-deficient (MCD) diet had higher serum ALT and AST activities and lower hepatic triglyceride levels than wild-type (WT) mice fed MCD diet. Expression of genes involved in inflammation (VCAM-1) and fibrosis (α-SMA) was increased in FXR{sup −/−} mice fed MCD diet (FXR{sup −/−}/MCD) compared to WT mice fed MCD diet (WT/MCD). Although MCD diet significantly induced hepatic fibrosis in terms of liver histology, FXR{sup −/−}/MCD mice showed less degree of hepatic steatosis than WT/MCD mice. Moreover, FXR deficiency synergistically potentiated the elevation effects of MCD diet on serum and hepatic bile acids levels. The super-physiological concentrations of hepatic bile acids in FXR{sup −/−}/MCD mice inhibited the expression of genes involved in fatty acid uptake and triglyceride accumulation, which may be an explanation for less steatosis in FXR{sup −/−}/MCD mice in contrast to WT/MCD mice. These results suggest that hepatic bile acids accumulation could override simple steatosis in hepatic injury during the progression of NAFLD and further emphasize the role of FXR in maintaining hepatic bile acid homeostasis in liver disorders and in hepatic protection.

  3. "Hepatitis" - Prevention and management in dental practice.

    Science.gov (United States)

    Dahiya, Parveen; Kamal, Reet; Sharma, Varun; Kaur, Saravpreet

    2015-01-01

    Today, viral hepatitis has become a silent epidemic worldwide. It is the major cause of liver cirrhosis and liver carcinoma. In a dental office, infections can be expedited through several routes, including direct or indirect contact with blood, oral fluids, droplet splatter, aerosols, etc. The aim of the present review is to increase the awareness among dental practitioners, so as to reduce the burden of hepatitis in their community. Electronic databases like PubMed, Medline, ProQuest, etc. were searched using the keywords hepatitis, dentist, liver disease, and infection control. Manual search of various journals and books was also carried out. Only highly relevant articles from English literature were considered for the present review. The results revealed that the dentists were among the high-risk groups for hepatitis, and they have little information on the factors associated with adherence to hepatitis B vaccination. A dentist can play a major role in the prevention of hepatitis by considering each and every patient as a potential carrier of hepatitis. Proper infection control, sterilization, and prophylactic vaccination protocols should be followed in order to reduce the risk of hepatitis.

  4. The study of the mechanism of arsenite toxicity in respiration-deficient cells reveals that NADPH oxidase-derived superoxide promotes the same downstream events mediated by mitochondrial superoxide in respiration-proficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Guidarelli, Andrea; Fiorani, Mara; Carloni, Silvia; Cerioni, Liana; Balduini, Walter; Cantoni, Orazio, E-mail: orazio.cantoni@uniurb.it

    2016-09-15

    We herein report the results from a comparative study of arsenite toxicity in respiration-proficient (RP) and -deficient (RD) U937 cells. An initial characterization of these cells led to the demonstration that the respiration-deficient phenotype is not associated with apparent changes in mitochondrial mass and membrane potential. In addition, similar levels of superoxide (O{sub 2}{sup .-}) were generated by RP and RD cells in response to stimuli specifically triggering respiratory chain-independent mitochondrial mechanisms or extramitochondrial, NADPH-oxidase dependent, mechanisms. At the concentration of 2.5 μM, arsenite elicited selective formation of O{sub 2}{sup .-} in the respiratory chain of RP cells, with hardly any contribution of the above mechanisms. Under these conditions, O{sub 2}{sup .-} triggered downstream events leading to endoplasmic reticulum (ER) stress, autophagy and apoptosis. RD cells challenged with similar levels of arsenite failed to generate O{sub 2}{sup .-} because of the lack of a functional respiratory chain and were therefore resistant to the toxic effects mediated by the metalloid. Their resistance, however, was lost after exposure to four fold greater concentrations of arsenite, coincidentally with the release of O{sub 2}{sup .-} mediated by NADPH oxidase. Interestingly, extramitochondrial O{sub 2}{sup .-} triggered the same downstream events and an identical mode of death previously observed in RP cells. Taken together, the results obtained in this study indicate that arsenite toxicity is strictly dependent on O{sub 2}{sup .-} availability that, regardless of whether generated in the mitochondrial or extramitochondrial compartments, triggers similar downstream events leading to ER stress, autophagy and apoptosis. - Highlights: • Mitochondrial superoxide mediates arsenite toxicity in respiration-proficient cells. • NADPH-derived superoxide mediates arsenite toxicity in respiration-deficient cells. • Arsenite causes apoptosis

  5. Prevalence of hepatitis B and C virus in surgical patients

    International Nuclear Information System (INIS)

    Ali, S.A.; Shah, F.A.; Ahmed, S.K.

    2006-01-01

    To assess the current prevalence of Hepatitis B and C virus in our set up. All patients who were operated during the study period. The detailed information about each patient was entered on a pre-designed questionnaire, including age, sex, type of operation, HBV and HCV screening test results, and presence of risk factors like: history of drug addiction, blood transfusion, family history of hepatitis, tattooing, viral vaccination, hospitalization, previous surgery, haemodialysis, etc. Amongst the total 275 patients, 27 (9.8%) had the Hepatitis virus: HBV-10, HCV-14 and HBV and HCV-3. Infection was more common among male patients and those between the ages of 41-50 years. Knowledge about Hepatitis risk factors is deficient, hence there should be more emphasis on public mass education programmes. Besides HBV vaccination should be carried out to reduce Hepatitis transmission. (author)

  6. Early transcriptomic changes induced by magnesium deficiency in Arabidopsis thaliana reveal the alteration of circadian clock gene expression in roots and the triggering of abscisic acid-responsive genes.

    Science.gov (United States)

    Hermans, Christian; Vuylsteke, Marnik; Coppens, Frederik; Craciun, Adrian; Inzé, Dirk; Verbruggen, Nathalie

    2010-07-01

    *Plant growth and development ultimately depend on environmental variables such as the availability of essential minerals. Unravelling how nutrients affect gene expression will help to understand how they regulate plant growth. *This study reports the early transcriptomic response to magnesium (Mg) deprivation in Arabidopsis. Whole-genome transcriptome was studied in the roots and young mature leaves 4, 8 and 28 h after the removal of Mg from the nutrient solution. *The highest number of regulated genes was first observed in the roots. Contrary to other mineral deficiencies, Mg depletion did not induce a higher expression of annotated genes in Mg uptake. Remarkable responses include the perturbation of the central oscillator of the circadian clock in roots and the triggering of abscisic acid (ABA) signalling, with half of the up-regulated Mg genes in leaves being ABA-responsive. However, no change in ABA content was observed. *The specificity of the response of some Mg-regulated genes was challenged by studying their expression after other mineral deficiencies and environmental stresses. The possibility to develop markers for Mg incipient deficiency is discussed here.

  7. Senescence marker protein-30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis

    Directory of Open Access Journals (Sweden)

    Yoshitaka Kondo

    2014-01-01

    Full Text Available Superoxide dismutase 1 (SOD1 is an antioxidant enzyme that converts superoxide anion radicals into hydrogen peroxide and molecular oxygen. The senescence marker protein-30 (SMP30 is a gluconolactonase that functions as an antioxidant protein in mammals due to its involvement in ascorbic acid (AA biosynthesis. SMP30 also participates in Ca2+ efflux by activating the calmodulin-dependent Ca2+-pump. To reveal the role of oxidative stress in lipid metabolism defects occurring in non-alcoholic fatty liver disease pathogenesis, we generated SMP30/SOD1-double knockout (SMP30/SOD1-DKO mice and investigated their survival curves, plasma and hepatic lipid profiles, amounts of hepatic oxidative stress, and hepatic protein levels expressed by genes related to lipid metabolism. While SMP30/SOD1-DKO pups had no growth retardation by 14 days of age, they did have low plasma and hepatic AA levels. Thereafter, 39% and 53% of male and female pups died by 15–24 and 89 days of age, respectively. Compared to wild type, SMP30-KO and SOD1-KO mice, by 14 days SMP30/SOD1-DKO mice exhibited: (1 higher plasma levels of triglyceride and aspartate aminotransferase; (2 severe accumulation of hepatic triglyceride and total cholesterol; (3 higher levels of superoxide anion radicals and thiobarbituric acid reactive substances in livers; and (4 decreased mRNA and protein levels of Apolipoprotein B (ApoB in livers – ApoB is an essential component of VLDL secretion. These results suggest that high levels of oxidative stress due to concomitant deficiency of SMP30 and/or AA, and SOD1 cause abnormal plasma lipid metabolism, hepatic lipid accumulation and premature death resulting from impaired VLDL secretion.

  8. NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

    Directory of Open Access Journals (Sweden)

    Joshua M. Baughman

    2016-07-01

    Full Text Available We introduce neutron-encoded (NeuCode amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model of Bap1, a tumor suppressor and deubiquitinase whose in vivo roles outside of cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation of cholesterol biosynthetic machinery coincident with reduced expression of gluconeogenic and lipid homeostasis proteins in liver. Bap1 loss increased pancreatitis biomarkers and reduced expression of mitochondrial proteins. These alterations accompany a metabolic remodeling with hypoglycemia, hypercholesterolemia, hepatic lipid loss, and acinar cell degeneration. Liver-specific Bap1 null mice present with fully penetrant perinatal lethality, severe hypoglycemia, and hepatic lipid deficiency. This work reveals Bap1 as a metabolic regulator in liver and pancreas, and it establishes NeuCode as a reliable proteomic method for deciphering in vivo biology.

  9. Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption

    DEFF Research Database (Denmark)

    Dore, Gregory J; Soriano, Vicente; Rockstroh, Jürgen

    2010-01-01

    .0002), nondetectable HBV DNA at baseline (P = 0.007), and black race (P = 0.03). Time to ART reinitiation was shorter (7.5, 15.6, and 17.8 months; P hepatitis C virus-positive and non-HBV/hepatitis...... C virus participants in the drug conservation arm. No hepatic decompensation events occurred among HBV-positive participants in either arm. CONCLUSION: HBV DNA rebound following ART interruption is common and may be associated with accelerated immune deficiency in HIV-HBV-coinfected patients.......BACKGROUND: The impact of antiretroviral therapy (ART) interruption in HIV-hepatitis B virus (HBV)-coinfected patients was examined in the Strategic Management of AntiRetroviral Therapy (SMART) study. METHODS: Plasma HBV DNA was measured in all hepatitis B surface antigen-positive (HBV...

  10. Diabetes and Hepatitis B Vaccination

    Science.gov (United States)

    Diabetes and Hepatitis B Vaccination Information for Diabetes Educators What is hepatitis B? Hepatitis B is a contagious liver disease that results from infection with the hepatitis B virus. When first infected, a person can develop ...

  11. Hepatitis Information for the Public

    Science.gov (United States)

    ... Hepatitis Contact Us Anonymous Feedback Quick Links to Hepatitis … A | B | C | D | E Viral Hepatitis Home ... Local Partners & Grantees Policy and Programs Resource Center Hepatitis Information for the Public Recommend on Facebook Tweet ...

  12. Immunoglobulins for preventing hepatitis A

    DEFF Research Database (Denmark)

    Liu, Jian Ping; Nikolova, Dimitrinka; Fei, Yutong

    2009-01-01

    Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention.......Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention....

  13. Gender affects skin wound healing in plasminogen deficient mice

    DEFF Research Database (Denmark)

    Rønø, Birgitte; Engelholm, Lars Henning; Lund, Leif Røge

    2013-01-01

    closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds...... functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency...... or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... fatigue or tiredness, shortness of breath, or chest pain. If your doctor diagnoses you with iron-deficiency ... Common symptoms of iron-deficiency anemia include: Chest pain Coldness in the hands and feet Difficulty concentrating ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, such as ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

  16. Factor VII deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000548.htm Factor VII deficiency To use the sharing features on this page, please enable JavaScript. Factor VII (seven) deficiency is a disorder caused by a ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... lead to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. People ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... view the colon directly. What if my doctor thinks something else is causing my iron-deficiency anemia? ... deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... mg and women need 18 mg. After age 51, both men and women need 8 mg. Pregnant ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia. These conditions include: Intestinal and digestive conditions, such as celiac disease; inflammatory bowel diseases, ... iron-deficiency anemia , such as bleeding in the digestive or urinary tract or heavy menstrual bleeding, your ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ... the size of your liver and spleen. Blood tests Based on results from blood tests to screen ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, lean red meat, ... signs of iron-deficiency anemia include: Brittle nails ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ...

  6. Fire Safety Deficiencies

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of all fire safety deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... learning how having iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... leaving cells where it is stored or from being absorbed in the duodenum, the first part of ... treatments for iron-deficiency anemia. Living With After being diagnosed with iron-deficiency anemia, it is important ...

  10. Microbiological diagnostics of viral hepatitis

    OpenAIRE

    HASDEMİR, Ufuk

    2016-01-01

    Viral hepatitis is an infection that primarily affects the liverbut may also have systemic clinical manifestations. The vastmajority of viral hepatitis are caused by one of five hepatotropicviruses: hepatitis A virus (HAV), hepatitis B virus (HBV),hepatitis C virus (HCV), hepatitis D (delta) virus (HDV), andhepatitis E virus (HEV) (Table I) [1]. HBV, HCV, and HDValso cause chronic hepatitis, whereas HAV does not. HEVcauses acute hepatitis in normal hosts but can cause protractedand chronic he...

  11. Extensive Mutagenesis of the Conserved Box E Motif in Duck Hepatitis B Virus P Protein Reveals Multiple Functions in Replication and a Common Structure with the Primer Grip in HIV-1 Reverse Transcriptase

    OpenAIRE

    Wang, Yong-Xiang; Luo, Cheng; Zhao, Dan; Beck, Jürgen; Nassal, Michael

    2012-01-01

    Hepadnaviruses, including the pathogenic hepatitis B virus (HBV), replicate their small DNA genomes through protein-primed reverse transcription, mediated by the terminal protein (TP) domain in their P proteins and an RNA stem-loop, ϵ, on the pregenomic RNA (pgRNA). No direct structural data are available for P proteins, but their reverse transcriptase (RT) domains contain motifs that are conserved in all RTs (box A to box G), implying a similar architecture; however, experimental support for...

  12. [Viral hepatitis in travellers].

    Science.gov (United States)

    Abreu, Cândida

    2007-01-01

    Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... if you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron-deficiency anemia because of your age, ... or sex. Age You may be at increased risk for iron deficiency at certain ages: Infants between ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español ... bleeding Consuming less than recommended daily amounts of iron Iron-deficiency anemia can be caused by getting ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Topics News & Resources Intramural Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer ... and symptoms as well as complications from iron-deficiency anemia. Research for Your Health The NHLBI is part of the U.S. Department ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia, your doctor may order the following blood tests to diagnose iron-deficiency anemia: Complete blood count (CBC) to ... than normal when viewed under a microscope. Different tests help your doctor diagnose iron-deficiency anemia. In iron-deficiency anemia, blood ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ...

  18. Hepatitis virus panel

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003558.htm Hepatitis virus panel To use the sharing features on this page, please enable JavaScript. The hepatitis virus panel is a series of blood tests used ...

  19. Hepatitis B - children

    Science.gov (United States)

    ... B children; HBV children; Pregnancy - hepatitis B children; Maternal transmission - hepatitis B children ... growth and development. Regular monitoring plays an important role in managing the disease in children. You should ...

  20. Hepatitis E Virus

    African Journals Online (AJOL)

    Before the discovery of hepatitis E virus (HEV), many epidemics of hepatitis in ... HEV was discovered in 1983 in the ... HEV infection is increased by HIV infection in pregnancy. (Caron et al. .... immunosuppressive therapy on the natural history.

  1. Delta agent (Hepatitis D)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000216.htm Hepatitis D (Delta agent) To use the sharing features on this page, please enable JavaScript. Hepatitis D is a viral infection caused by the ...

  2. Hepatitis A Test

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Hepatitis A Testing Send Us Your Feedback Choose Topic At ... IgG HAV-Ab total Anti-HAV Formal Name Viral Hepatitis A Antibody This article was last reviewed on ...

  3. Hepatic falciform artery

    International Nuclear Information System (INIS)

    Jaques, Paul F.; Mauro, Matthew A.; Sandhu, Jeet

    1997-01-01

    The hepatic falciform artery is an occasional terminal branch of the left or middle hepatic artery, and may provide an uncommon but important collateral route when the principal visceral arteries are occluded

  4. Hepatitis A -- children

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007670.htm Hepatitis A - children To use the sharing features on this page, please enable JavaScript. Hepatitis A in children is swelling and inflamed tissue of ...

  5. Hepatitis B Foundation Newsletter: B Informed

    Science.gov (United States)

    ... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  6. Surveillance for Viral Hepatitis - United States, 2014

    Science.gov (United States)

    ... Resource Center Anonymous Feedback Viral Hepatitis Surveillance for Viral Hepatitis – United States, 2014 Recommend on Facebook Tweet Share ... Cases Hepatitis A Hepatitis B Hepatitis C Discussion Hepatitis A virus Index PAGE DESCRIPTION Table 2.1 Reported ...

  7. Aberrant hepatic artery

    International Nuclear Information System (INIS)

    Konstam, M.A.; Novelline, R.A.; Athanasoulis, C.A.

    1979-01-01

    In a patient undergoing selective hepatic arteriography for suspected liver trauma, a nonopacified area of the liver, initially thought to represent a hepatic hematoma, was later discovered to be due to the presence of an accessory right hepatic artery arising from the superior mesenteric artery. This case illustrates the need for a search for aberrant vasculature whenever a liver hematoma is suspected on the basis of a selective hepatic arteriogram. (orig.) [de

  8. Hepatic infarction in HELLP syndrome; a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Jeong; Kim, Hong [Keimyung Univ. School of Medicine, Taegu (Korea, Republic of)

    2000-11-01

    Hepatic infarction is a rare but potentially life-threatening complication of pregnancy-associated preeclampsia or HELLP (hemolysis, elevated liver function tests, low platelets) syndrome. We present a case of hepatic infarction subsequent to HELLP syndrome and occurring during the immediate postpartum, and the associated radiologic findings. Sonography revealed poorly defined hypoechoic zones of infarction. Computed tomography(CT) demonstrated the characteristic features of nonenhancing, low attenuation, relatively well-defined, wedge shaped or geographic hepatic lesions, without mass effect.

  9. Hepatic infarction in HELLP syndrome; a case report

    International Nuclear Information System (INIS)

    Kim, Mi Jeong; Kim, Hong

    2000-01-01

    Hepatic infarction is a rare but potentially life-threatening complication of pregnancy-associated preeclampsia or HELLP (hemolysis, elevated liver function tests, low platelets) syndrome. We present a case of hepatic infarction subsequent to HELLP syndrome and occurring during the immediate postpartum, and the associated radiologic findings. Sonography revealed poorly defined hypoechoic zones of infarction. Computed tomography(CT) demonstrated the characteristic features of nonenhancing, low attenuation, relatively well-defined, wedge shaped or geographic hepatic lesions, without mass effect

  10. Distal renal tubular acidosis and hepatic lipidosis in a cat.

    Science.gov (United States)

    Brown, S A; Spyridakis, L K; Crowell, W A

    1986-11-15

    Clinical and laboratory evidence of hepatic failure was found in a chronically anorectic cat. Simultaneous blood and urine pH determinations established a diagnosis of distal renal tubular acidosis. The cat did not respond to treatment. Necropsy revealed distal tubular nephrosis and hepatic lipidosis. The finding of distal renal tubular acidosis in a cat with hepatic lipidosis emphasizes the importance of complete evaluation of acid-base disorders in patients.

  11. Right Hepatic Artery: A Cadaver Investigation and Its Clinical Significance

    Directory of Open Access Journals (Sweden)

    Usha Dandekar

    2015-01-01

    Full Text Available The right hepatic artery is an end artery and contributes sole arterial supply to right lobe of the liver. Misinterpretation of normal anatomy and anatomical variations of the right hepatic artery contribute to the major intraoperative mishaps and complications in hepatobiliary surgery. The frequency of inadvertent or iatrogenic hepatobiliary vascular injury rises with the event of an aberrant anatomy. This descriptive study was carried out to document the normal anatomy and different variations of right hepatic artery to contribute to existing knowledge of right hepatic artery to improve surgical safety. This study conducted on 60 cadavers revealed aberrant replaced right hepatic artery in 18.3% and aberrant accessory right hepatic artery in 3.4%. Considering the course, the right hepatic artery ran outside Calot’s triangle in 5% of cases and caterpillar hump right hepatic artery was seen in 13.3% of cases. The right hepatic artery (normal and aberrant crossed anteriorly to the common hepatic duct in 8.3% and posteriorly to it in 71.6%. It has posterior relations with the common bile duct in 16.7% while in 3.4% it did not cross the common hepatic duct or common bile duct. The knowledge of such anomalies is important since their awareness will decrease morbidity and help to keep away from a number of surgical complications.

  12. Hepatitis viruses overview

    African Journals Online (AJOL)

    Hepatitis is major cause of morbidity or mortality worldwide, particularly in the developing world. The major causes of infective hepatitis are hepatitis viruses. A, B, C, D or E. In the acute phase, there are no clinical features that can reliably differentiate between these viruses. Infection may be asymptomatic or can present as.

  13. Hepatitis B Test

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Hepatitis B Testing Send Us Your Feedback Choose Topic At ... Known As HBV Tests Hep B anti-HBs Hepatitis B Surface Antibody HBsAg Hepatitis B Surface Antigen HBeAg ...

  14. Experimental induction of hepatic lipidosis in cats.

    Science.gov (United States)

    Biourge, V C; Groff, J M; Munn, R J; Kirk, C A; Nyland, T G; Madeiros, V A; Morris, J G; Rogers, Q R

    1994-09-01

    The effect of long-term voluntary fasting on hematologic variables, biochemical profiles, and liver histologic findings was assessed in 15 obese cats (> 40% overweight). Clinical signs and laboratory results consistent with hepatic lipidosis were observed in 12 of 15 cats after 5 to 7 weeks of fasting, and were associated with 30 to 35% reduction of initial body weight. Histologic examination of successive liver biopsy specimens revealed that obesity was not associated with liver parenchymal lipid accumulation, but that fasting resulted in lipidosis in all 15 cats. The long-term fast was associated with an early (after 2 to 4 weeks of fasting) and significant (P hepatic-associated enzyme activities and in total and direct serum bilirubin concentrations. Significant (P hepatic lipidosis, cats appeared to tolerate the fast without other adverse effect. This study confirmed that long-term fasting may induce clinical hepatic lipidosis in obese cats. Fasting appears to induce a syndrome of hepatic lipidosis that is indistinguishable from feline idiopathic hepatic lipidosis and may be an appropriate model to study the pathophysiologic features and treatment of hepatic lipidosis.

  15. Delayed Hepatic Adaptation to Weaning in ACBP(-/-) Mice Is Caused by Disruption of the Epidermal Barrier

    DEFF Research Database (Denmark)

    Neess, Ditte; Bek, Signe; Bloksgaard, Maria

    2013-01-01

    in the skin rather than in the liver. Similarly to ACBP(-/-) mice, K14-ACBP(-/-) mice exhibit an increased transepidermal water loss, and we show that the hepatic phenotype is caused specifically by the epidermal barrier defect, which leads to increased lipolysis in white adipose tissue. Our data demonstrate......We previously reported that mice deficient in acyl-CoA-binding protein (ACBP) display a delayed metabolic adaptation to weaning. This includes a delayed activation of the hepatic lipogenic gene program, which may result from hepatic accumulation of triacylglycerol and/or cholesteryl esters...... in the late suckling period. To further investigate the basis for this phenotype, we generated mice deficient in ACBP in hepatocytes (Alb-ACBP(-/-)) and keratinocytes (K14-ACBP(-/-)). Surprisingly, the delayed adaptation to weaning, including hepatic lipid accumulation, is caused by ACBP deficiency...

  16. Matrix metalloproteinase-14 mediates formation of bile ducts and hepatic maturation of fetal hepatic progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Otani, Satoshi [Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo (Japan); Kakinuma, Sei, E-mail: skakinuma.gast@tmd.ac.jp [Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo (Japan); Department for Liver Disease Control, Tokyo Medical and Dental University, Tokyo (Japan); Kamiya, Akihide [Institute of Innovative Science and Technology, Tokai University, Isehara (Japan); Goto, Fumio; Kaneko, Shun; Miyoshi, Masato; Tsunoda, Tomoyuki; Asano, Yu; Kawai-Kitahata, Fukiko; Nitta, Sayuri; Nakata, Toru; Okamoto, Ryuichi; Itsui, Yasuhiro; Nakagawa, Mina; Azuma, Seishin [Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo (Japan); Asahina, Yasuhiro [Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo (Japan); Department for Liver Disease Control, Tokyo Medical and Dental University, Tokyo (Japan); Yamaguchi, Tomoyuki [Division of Stem Cell Therapy, Institute of Medical Science, The University of Tokyo, Tokyo (Japan); Koshikawa, Naohiko [Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Tokyo (Japan); Seiki, Motoharu [Medical School, Kanazawa University, Kanazawa (Japan); Nakauchi, Hiromitsu [Division of Stem Cell Therapy, Institute of Medical Science, The University of Tokyo, Tokyo (Japan); and others

    2016-01-22

    Fetal hepatic stem/progenitor cells, called hepatoblasts, play central roles in liver development; however, the molecular mechanisms regulating the phenotype of these cells have not been completely elucidated. Matrix metalloproteinase (MMP)-14 is a type I transmembrane proteinase regulating pericellular proteolysis of the extracellular matrix and is essential for the activation of several MMPs and cytokines. However, the physiological functions of MMP-14 in liver development are unknown. Here we describe a functional role for MMP-14 in hepatic and biliary differentiation of mouse hepatoblasts. MMP-14 was upregulated in cells around the portal vein in perinatal stage liver. Formation of bile duct-like structures in MMP-14–deficient livers was significantly delayed compared with wild-type livers in vivo. In vitro biliary differentiation assays showed that formation of cholangiocytic cysts derived from MMP-14–deficient hepatoblasts was completely impaired, and that overexpression of MMP-14 in hepatoblasts promoted the formation of bile duct-like cysts. In contrast, the expression of molecules associated with metabolic functions in hepatocytes, including hepatic nuclear factor 4α and tryptophan 2,3-dioxygenase, were significantly increased in MMP-14–deficient livers. Expression of the epidermal growth factor receptor and phosphorylation of mitogen-activated protein kinases were significantly upregulated in MMP-14–deficient livers. We demonstrate that MMP-14–mediated signaling in fetal hepatic progenitor cells promotes biliary luminal formation around the portal vein and negatively controls the maturation of hepatocytes. - Highlights: • Loss of MMP-14 delayed formation of bile duct-like structures in perinatal liver. • Overexpression of MMP-14 in hepatobalsts promoted the biliary formation in vitro. • Loss of MMP-14 promoted hepatocyte maturation of hepatoblasts in vivo. • MMP-14–mediated signaling regulates terminal differentiation of

  17. Alcoholic hepatitis.

    Science.gov (United States)

    Damgaard Sandahl, Thomas

    2014-10-01

    Alcoholic hepatitis (AH) is an acute inflammatory syndrome causing significant morbidity and mortality. The prognosis is strongly dependent on disease severity, as assessed by clinical scoring systems. Reliable epidemiological data as well as knowledge of the clinical course of AH are essential for planning and resource allocation within the health care system. Likewise, individual evaluation of risk is desirable in the clinical handling of patients with AH as it can guide treatment, improve patient information, and serve as strata in clinical trials. The present PhD thesis is based on three studies using a cohort of nearly 2000 patients diagnosed with AH in Denmark from 1999 to 2008 as a cohort, in a population-based study design. The aims of this thesis were as follows. (1) To describe the incidence and short- and long-term mortality, of AH in Denmark (Study I). (2) To validate and compare the ability of the currently available prognostic scores to predict mortality in AH (Study II). (3) To investigate the short- and long-term causes of death of patients with AH (Study III). During the study decade, the annual incidence rate in the Danish population rose from 37 to 46 per 106 for men and from 24 to 34 per 106 for women. Both short- and long-term mortality rose for men and women, and the increase in short-term mortality was attributable to increasing patient age and prevalence of cirrhosis. Our evaluation of the most commonly used prognostic scores for predicting the mortality of patients with AH showed that all scores performed similarly, with Area under the Receiver Operator Characteristics curves giving values between 0.74 and 0.78 for 28-day mortality assessed on admission. Our study on causes of death showed that in the short-term (thesis provides novel warranted epidemiological information about AH that shows increasing incidence and mortality rates. Consequently, it reiterates the fact that AH is a life-threatening disease and suggests that AH is an

  18. Proteomic analysis reveals differential accumulation of small heat shock proteins and late embryogenesis abundant proteins between ABA-deficient mutant vp5 seeds and wild-type Vp5 seeds in maize

    Directory of Open Access Journals (Sweden)

    Xiaolin eWu

    2015-01-01

    Full Text Available ABA is a major plant hormone that plays important roles during many phases of plant life cycle, including seed development, maturity and dormancy, and especially the acquisition of desiccation tolerance. Understanding of the molecular basis of ABA-mediated plant response to stress is of interest not only in basic research on plant adaptation but also in applied research on plant productivity. Maize mutant viviparous-5 (vp5, deficient in ABA biosynthesis in seeds, is a useful material for studying ABA-mediated response in maize. Due to carotenoid deficiency, vp5 endosperm is white, compared to yellow Vp5 endosperm. However, the background difference at proteome level between vp5 and Vp5 seeds is unclear. This study aimed to characterize proteome alterations of maize vp5 seeds and to identify ABA-dependent proteins during seed maturation. We compared the embryo and endosperm proteomes of vp5 and Vp5 seeds by gel-based proteomics. Up to 46 protein spots, most in embryos, were found to be differentially accumulated between vp5 and Vp5. The identified proteins included small heat shock proteins (sHSPs, late embryogenesis abundant (LEA proteins, stress proteins, storage proteins and enzymes among others. However, EMB564, the most abundant LEA protein in maize embryo, accumulated in comparable levels between vp5 and Vp5 embryos, which contrasted to previously characterized, greatly lowered expression of emb564 mRNA in vp5 embryos. Moreover, LEA proteins and sHSPs displayed differential accumulations in vp5 embryos: six out of eight identified LEA proteins decreased while nine sHSPs increased in abundance. Finally, we discussed the possible causes of global proteome alterations, especially the observed differential accumulation of identified LEA proteins and sHSPs in vp5 embryos. The data derived from this study provides new insight into ABA-dependent proteins and ABA-mediated response during maize seed maturation.

  19. Pathogenesis of Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Irena Ciećko-Michalska

    2012-01-01

    Full Text Available Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.

  20. Pathogenesis of Hepatic Encephalopathy

    Science.gov (United States)

    Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

    2012-01-01

    Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

  1. Fulminant hepatic failure in children: Etiology, histopathology and MDCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Cakir, Banu [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: banutopcu@yahoo.com; Kirbas, Ismail [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: drismailk@yahoo.com; Demirhan, Beyhan [Baskent University Faculty of Medicine Department of Pathology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: beyhand@baskent-ank.edu.tr; Tarhan, Nefise Cagla [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: caglat@gmail.com; Bozkurt, Alper [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: abozkurt78@hotmail.com; Ozcay, Figen [Baskent University Faculty of Medicine Department of Pediatric Gastroenterology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: fozcay@baskent.edu.tr; Coskun, Mehmet [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: mcoskun@baskent-ank.edu.tr

    2009-11-15

    Introduction: The purpose of this study is to determine the etiologies, histopathology and MDCT findings of children with fulminant hepatic failure admitted to our institution. Materials and methods: Between June 2004 and November 2006, 15 children with fulminant hepatic failure who underwent MDCT were included retrospectively in this study. Twelve patients had liver biopsies. The patients were divided into three groups as hyperacute (Group I), acute (Group II) and subacute (Group III) depending on onset of hepatic encephalopathy. Results: Hepatitis A in 4 patients, non-A, non-E hepatitis in 4; mushroom poisoning in 3; fulminant Wilson's disease in 2; autoimmune hepatitis in 1; and both hepatitis B and toxic hepatitis (with leflunomide treatment) in 1 patient were detected. MDCT of all three groups revealed diffuse reduction in hepatic attenuation in 11 patients; ascites in 9; periportal edema in 6; edema of gallbladder wall in 6; splenomegaly in 6; heterogeneous hepatic parenchyma in 6; hepatomegaly in 3; irregular contours of liver in 2; multiple micronodules in 1 and necrotic areas and regeneration in liver parenchyma in 2 patients. Histopathologic evaluation of liver biopsies showed massive hepatic necrosis, inflammatory cell infiltration and ductular proliferation in 8 patients, periportal edema in 6, edema of gallbladder wall in 5, regenerating nodules and fibrous septa consistent with cirrhotic pattern in 2, and regenerating nodules and necrotic areas in 2 patients. Conclusion: The most common MDCT findings in fulminant hepatic failure were diffuse reduction in hepatic attenuation and ascites. Massive hepatic necrosis was the most common histopathologic finding.

  2. Disruption of redox homeostasis in liver function and activation of apoptosis on consumption of aspartame in folate deficient rat model

    Directory of Open Access Journals (Sweden)

    Ashok Iyaswamy

    2017-06-01

    Full Text Available This study assesses the effect of long-term intake of aspartame on liver function and apoptosis signaling pathway in the Wistar albino rats. Several reports have suggested that methanol is one of the major metabolites of Aspartame. Non-primate animals are usually resistant to methanol-induced metabolic acidosis due to high levels of hepatic folate content; hence a folate deficiency model was induced by treating animals with methotrexate (MTX prior to aspartame exposure. The aspartame treated MTX animals exhibited a marked significant increase in hepatic alanine transaminase (ALT, aspartate transaminase (AST, alkaline phosphatase (ALP and lactic acid dehydrogenase (LDH activity compared to controls. Aspartame treated MTX animals additionally exhibited down-regulation of genes namely B-cell lymphoma 2 (Bcl2 expression and up-regulation of Bcl-2-associated X protein (Bax, Fas-associated protein with death domain (FADD and Caspase 3, 9 genes and apoptotic protein expression, indicating the augmentation of hepatic apoptosis. Nuclear condensation, micro vacuole formation in the cytoplasm and necrosis were observed in the liver of the aspartame treated animals on histopathology evaluation. Additionally, Immunohistochemical analysis revealed a significant increase in positive cells expressing Fas, FADD, Bax and Caspase 9 protein, indicating an increase in apoptotic protein expression in the liver. Thus, Aspartame may act as a chemical stressor which alters the functional status of liver, leading to hepatotoxicity.

  3. Protozoal hepatitis in a western burrowing owl (Athene cunicularia hypugaea)

    Science.gov (United States)

    Franson, J. Christian

    2017-01-01

    A western burrowing owl (Athene cunicularia hypugaea) found dead in southern California had many light-colored lesions visible grossly on its liver, and histopathology revealed extensive necrosis throughout the hepatic parenchyma. Single-celled organisms were seen in clear spaces within the areas of necrosis. The owl was diagnosed with protozoal hepatitis.

  4. A Case of Typhoid Fever with Hepatic Granulomas and Enteritis

    Directory of Open Access Journals (Sweden)

    Shraddha Narechania

    2015-01-01

    Full Text Available The common histopathologic hepatic manifestations in patients infected with Salmonella include cloudy swelling and balloon degeneration with vacuolation of the hepatocytes and steatosis. Hepatic granulomas are a very rare finding, so far reported in very few cases. We report a 64-year-old patient with Salmonella enteritis who was found to have multiple 1.4 to 1.6 cm hypoechoic liver masses on ultrasound of the abdomen which on biopsy revealed hepatic granulomas. This case highlights the importance of keeping the differential diagnosis of Salmonella typhi (S. typhi in mind in a patient with hepatic granulomas.

  5. Occult hepatitis B infection: an evolutionary scenario

    Directory of Open Access Journals (Sweden)

    Lukashov Vladimir V

    2008-12-01

    Full Text Available Abstract Background Occult or latent hepatitis B virus (HBV infection is defined as infection with detectable HBV DNA and undetectable surface antigen (HBsAg in patients' blood. The cause of an overt HBV infection becoming an occult one is unknown. To gain insight into the mechanism of the development of occult infection, we compared the full-length HBV genome from a blood donor carrying an occult infection (d4 with global genotype D genomes. Results The phylogenetic analysis of polymerase, core and X protein sequences did not distinguish d4 from other genotype D strains. Yet, d4 surface protein formed the evolutionary outgroup relative to all other genotype D strains. Its evolutionary branch was the only one where accumulation of substitutions suggests positive selection (dN/dS = 1.3787. Many of these substitutiions accumulated specifically in regions encoding the core/surface protein interface, as revealed in a 3D-modeled protein complex. We identified a novel RNA splicing event (deleting nucleotides 2986-202 that abolishes surface protein gene expression without affecting polymerase, core and X-protein related functions. Genotype D strains differ in their ability to perform this 2986-202 splicing. Strains prone to 2986-202 splicing constitute a separate clade in a phylogenetic tree of genotype D HBVs. A single substitution (G173T that is associated with clade membership alters the local RNA secondary structure and is proposed to affect splicing efficiency at the 202 acceptor site. Conclusion We propose an evolutionary scenario for occult HBV infection, in which 2986-202 splicing generates intracellular virus particles devoid of surface protein, which subsequently accumulates mutations due to relaxation of coding constraints. Such viruses are deficient of autonomous propagation and cannot leave the host cell until it is lysed.

  6. The Dynamics of Incidence of Chronic Hepatitis B and C in the Population of Almaty city for 2001-2014

    Directory of Open Access Journals (Sweden)

    Maria N. Omarova

    2016-09-01

    Full Text Available The results of a retrospective epidemiological analysis revealed a sharp decline in the incidence of acute hepatitis B among the entire population of Almaty and the absence of acute hepatitis B, acute hepatitis C and chronic hepatitis C among children under 14 years of age. We found an increased incidence of chronic hepatitis B and chronic hepatitis C among the population of Almaty. Assessment of the hepatitis C incidence by the cumulative indices more objectively reflects the epidemiological situation for this disease.

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... increased need for iron during growth spurts. Older adults, especially those over age ... athletes. Athletes, especially young females, are at risk for iron deficiency. Endurance ...

  8. Iodine deficiency disorders

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S M [Pakistan Council for Science and Technology, Islamabad (Pakistan)

    1994-12-31

    Iodine deficiency (IDD) is one of the common problem in the diet. Iodine deficiency as prevalence of goiter in population occurs in the mountainous areas. There is consensus that 800 million people are at risk of IDD from living in iodine deficient area and 190 million from goiter. Very high prevalence of IDD in different parts of the world are striking. It has generally observed that in iodine-deficient areas about 50% are affected with goiter, 1-5% from cretinsim and 20% from impaired mental and/or mortor function. (A.B.).

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

  10. The transport of triglycerides through the secretory pathway of hepatocytes is impaired in apolipoprotein E deficient mice.

    NARCIS (Netherlands)

    Mensenkamp, A.R.; Luyn, M.J.A. van; Havinga, R.; Teusink, B.; Waterman, I.J.; Mann, C.J.; Elzinga, B.M.; Verkade, H.J.; Zammit, V.A.; Havekes, L.M.; Shoulders, C.C.; Kuipers, F.

    2004-01-01

    BACKGROUND/AIMS: Apolipoprotein E (apoE)-deficient mice develop hepatic steatosis and secrete reduced levels of VLDL-TG. METHODS AND RESULTS: We examined the effects of apoE-deficiency on intracellular lipid homeostasis and secretion of triglycerides (TG). We show that intracellular TG turnover and

  11. The transport of triglycerides through the secretory pathway of hepatocytes is impaired in apolipoprotein E deficient mice

    NARCIS (Netherlands)

    Mensenkamp, AR; van Luyn, MJA; Havinga, R; Teusink, B; Waterman, IJ; Mann, CJ; Elzinga, BM; Verkade, HJ; Zammit, VA; Havekes, LM; Shoulders, CC; Kuipers, F

    Background/Aims: Apolipoprotein E (apoE)-deficient mice develop hepatic steatosis and secrete reduced levels of VLDL-TG. Methods and results: We examined the effects of apoE-deficiency on intracellular lipid homeostasis and secretion of triglycerides (TG). We show that intracellular TG turnover and

  12. [Latest Treatment of Viral Hepatitis--Overcoming Hepatitis C and Reactivation of Hepatitis B].

    Science.gov (United States)

    Tanaka, Yasuhito

    2016-02-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV), discovered as causative viruses of post-transfusion hepatitis, become persistent infections, leading to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). For HCV, recent IFN-free direct-acting antiviral (DAA) therapies have increased sustained virological response (SVR) rates and reduced adverse events. IFN-based therapies, still the standard of care in Asian countries, are influenced by IL28B genetic variants and the liver fibrosis stage, but the DAA combinations obscure the influence of these factors. These new therapies can eradicate HCV and prevent HCC development. On the other hand, it is difficult to eradicate HBV completely. Although HBV infection can be prevented by vaccination, reactivation of HBV following anti-cancer chemotherapy and immunosuppressive therapy is a well-known complication. HBV reactivation has been reported to be associated with anti-CD20 monoclonal antibody rituximab-containing chemotherapy and TNF-α inhibitor-containing immunosuppressive therapy in HBV-resolved patients. Our prospective observational study revealed that monthly monitoring of HBV DNA was useful for preventing HBV reactivation-related hepatitis among B-cell non-Hodgkin lymphoma patients with resolved HBV infection following rituximab-steroid-chemo, suggesting that preemptive therapy guided by serial HBV DNA monitoring should be recommended. Recently, highly sensitive HBsAg detection by Lumipulse HBsAg-HQ may be useful for several clinical applications. The sensitivity of this assay (5 mIU/mL) was approximately 10-fold higher than Abbott ARCHITECT, but still lower than HBV-DNA assays. The convenient HBsAg-HQ may be useful for detecting occult HBV infection and HBV reactivation in relatively low-risk groups except for those receiving rituximab-steroid-chemo. [

  13. Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export

    DEFF Research Database (Denmark)

    Kjølby, Mads Fuglsang; Andersen, Olav Michael; Breiderhoff, Tilman

    2010-01-01

    of lipoproteins from the liver and ameliorates hypercholesterolemia and atherosclerotic lesion formation in LDL receptor-deficient animals. In contrast, sortilin overexpression stimulates hepatic release of lipoproteins and increases plasma LDL levels. Our data have uncovered a regulatory pathway in hepatic...... lipoprotein export and suggest a molecular explanation for the cardiovascular risk being associated with 1p13.3. Udgivelsesdato: september 8...

  14. Assessment of a novel VEGF targeted agent using patient-derived tumor tissue xenograft models of colon carcinoma with lymphatic and hepatic metastases.

    Directory of Open Access Journals (Sweden)

    Ketao Jin

    Full Text Available The lack of appropriate tumor models of primary tumors and corresponding metastases that can reliably predict for response to anticancer agents remains a major deficiency in the clinical practice of cancer therapy. It was the aim of our study to establish patient-derived tumor tissue (PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastases useful for testing of novel molecularly targeted agents. PDTT of primary colon carcinoma, lymphatic and hepatic metastases were used to create xenograft models. Hematoxylin and eosin staining, immunohistochemical staining, genome-wide gene expression analysis, pyrosequencing, qRT-PCR, and western blotting were used to determine the biological stability of the xenografts during serial transplantation compared with the original tumor tissues. Early passages of the PDTT xenograft models of primary colon carcinoma, lymphatic and hepatic metastases revealed a high degree of similarity with the original clinical tumor samples with regard to histology, immunohistochemistry, genes expression, and mutation status as well as mRNA expression. After we have ascertained that these xenografts models retained similar histopathological features and molecular signatures as the original tumors, drug sensitivities of the xenografts to a novel VEGF targeted agent, FP3 was evaluated. In this study, PDTT xenograft models of colon carcinoma with lymphatic and hepatic metastasis have been successfully established. They provide appropriate models for testing of novel molecularly targeted agents.

  15. Ultrasonographic classification of Atypical hepatic hemangiomas

    International Nuclear Information System (INIS)

    Bae, Sang Jin; Kim, Pyo Nyun; Ha, Hyun Kwon; Lee, Moon Gyu; Auh, Yong Ho; Yoon, Kwon Ha

    2000-01-01

    Cavernous hemangioma is the most common benign hepatic tumor. Typically, the most common features revealed by ultrasound (US) include its small size (4 cm or less in diameter), uniform hyperechogenicity, well defined margins, position in the subcapsular region of the right lobe of the liver, and some posterior echo enhancement. In addition, follow-up scanning may reveal changes in size, though this is rare. The US findings of hepatic hemangiomas may vary, however, especially when lesions are large and/or multiple. For that reason, differential diagnosis between this condition and hepatocellular carcinomas, metastatic lesions, lymphomas and other tumors is difficult. An understanding of the various sonographic findings of hepatic hemangioma can facilitate the early detection of the condition. (author)

  16. Hepatic encephalopathy. Imaging Findings

    International Nuclear Information System (INIS)

    Carrillo, Maria Claudia; Bermudez Munoz, Sonia; J Morillo, Anibal

    2007-01-01

    Hepatic encephalopathy occurs in patients with chronic hepatic insufficiency and can produce abnormalities in the central nervous system, which can be observed in MRI studies. Traditionally, these imaging findings include symmetrical hyper intensities in T1-weighted sequences in the basal ganglia (mainly globus pallidus), involving also the substantia nigra, mesencephalic tegmentum, frontal and occipital cortex. These areas appear of normal intensity in T2-weighted imaging sequences. Other entities that can lead to similar findings include manganese intoxication and type-1 neurofibromatosis. Currently, with the advent of MR spectroscopy, abnormalities in patients with clinical and subclinical hepatic encephalopathy have been described. After hepatic transplantation, hyper intensities of the basal ganglia and the MR spectroscopic findings may disappear within 3 months to 1 year, suggesting a functional, more than a structural damage. This article will demonstrate the MR findings of patients with hepatic encephalopathy due to chronic hepatic insufficiency.

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... exploring about iron-deficiency anemia. Read more New treatments for disorders that lead to iron-deficiency anemia. We are ... and other pathways. This could help develop new therapies for conditions that ... behavior, thinking, and mood during adolescence. Treating anemia in ...

  18. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... loss and lead to iron-deficiency anemia. Common causes of blood loss that lead to iron-deficiency anemia include: Bleeding in your GI tract, from an ulcer, colon cancer, or regular use of medicines such as aspirin ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia. Search the NIH Research Portfolio Online Reporting Tools (RePORT) to learn about research that ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blocks the intestine from taking up iron. Other medical conditions Other medical conditions that may lead to iron-deficiency anemia ... daily amount of iron. If you have other medical conditions that cause iron-deficiency anemia , such as ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Are you curious about how inflammation from chronic diseases can cause iron-deficiency anemia? Read more When there is ... DBDR) is a leader in research on the causes, prevention, and treatment of blood diseases, including iron-deficiency anemia. Search the NIH Research ...

  4. Nutritional iron deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.; Hurrell, R.F.

    2007-01-01

    Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Topics section only, or the News and Resources section. NHLBI Entire Site NHLBI Entire Site Health ... español Iron-deficiency anemia is a common type of anemia that occurs if you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron is too ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ... check the size of your liver and spleen. Blood tests Based on results from blood tests to screen ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children who do not consume the daily recommended amount of iron. Read less Participate in NHLBI Clinical Trials We lead or sponsor many studies related to iron-deficiency anemia. See if you ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... en español Iron-deficiency anemia is a common type of anemia that occurs if you do not ... iron-deficiency anemia and help rule out other types of anemia. Treatment will explain treatment-related complications ...

  11. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.

    2015-01-01

    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia. Return to Signs, Symptoms, and Complications to review signs and symptoms as well as complications from iron-deficiency ... NIH]) Heavy Menstrual Bleeding (Centers for Disease Control and ... Dietary Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library ...

  13. Iron deficiency anemia

    Science.gov (United States)

    Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, ... you are experiencing side effects such as a bad metallic taste, vomiting, diarrhea, constipation, or upset stomach. ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... how we are using current research and advancing research to prevent iron-deficiency anemia. Participate in NHLBI Clinical Trials will explain our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and Complications ...

  16. Hepatic folate metabolism in the chronic alcoholic monkey

    International Nuclear Information System (INIS)

    Tamura, T.; Romero, J.J.; Watson, J.E.; Gong, E.J.; Halsted, C.H.

    1981-01-01

    To assess the role of altered hepatic folate metabolism in the pathogenesis of the folate deficiency of chronic alcoholism, the hepatic metabolism of a tracer dose of 3 H-PteGlu was compared in monkeys given 50% of energy as ethanol for 2 years and in control monkeys. Long-term ethanol feeding resulted in mild hepatic injury, with a significant decrease in hepatic folate levels. Chromatographic studies of liver biopsies obtained after the tracer dose indicated that the processes of reduction, methylation, and formylation of reduced folate and the synthesis of polyglutamyl folates were not affected by long-term ethanol feeding. Hepatic tritium levels were significantly decreased in the ethanol-fed group. These studies suggest that the decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decrease in hepatic folate levels observed after long-term ethanol ingestion is due to a decreased ability to retain folates in the liver, whereas reduction and further metabolism of folates is not affected

  17. Hepatitis isquémica Ischemic hepatitis

    Directory of Open Access Journals (Sweden)

    Marcos Amuchástegui (h

    2006-10-01

    Full Text Available La hepatitis isquémica es una complicación sumamente infrecuente de cirugía cardiovascular. Las biopsias muestran necrosis centrolobulillar. El término de "hepatitis" fue propuesto debido al aumento de transaminasas similar a aquellas de origen infeccioso, e "isquémica" por falla en la perfusión hepática. Posteriormente se definió el término de hepatitis isquémica como cuadro de elevación aguda y reversible (dentro de las 72 horas de transaminasas de hasta 20 veces el valor normal, asociado a trastornos en la perfusión hepática, luego de haber excluido otras causas de hepatitis aguda o daño hepatocelular. Se describe el caso de un paciente de 53 años que consulta por dolor epigástrico de 12 h de evolución sin fiebre, náuseas ni vómitos, resistente a la medicación. Tenía antecedentes inmediatos de reemplazo de válvula aórtica, y estaba anticoagulado. Evolucionó con shock y fallo multiorgánico. El examen evidenció marcada ictericia y signos de taponamiento pericárdico, asociado a un aumento considerable de enzimas hepáticas. Un ecocardiograma informó signos de taponamiento cardíaco y ausencia de disección aórtica. Se decidió pericardiocentesis, extrayéndose 970 cc. de líquido sanguinolento, y hemodiálisis, con notable mejoría de su estado hemodinámico. Los valores enzimáticos disminuyeron. Los marcadores virales fueron negativos.Ischemic hepatitis is an uncommon cardiovascular surgery complication. Hepatic biopsies show centrolobulillar necrosis. The term "hepatitis" was proposed because of a raise in hepatic enzymes similar with infectious disease, and "ischemic" because of failure in hepatic perfusion. Ischemic hepatitis was then defined as an acute and reversible elevation of hepatic enzymes (within 72 h, associated with disturbance in hepatic perfusion after excluding other causes of acute hepatitis. A 53 year-old male presented complaining of a 12 h epigastric pain, without nausea or vomiting, resistant

  18. Hepatic artery infusion (HAI) for hepatic metastases in combination with hepatic resection and hepatic radiation

    International Nuclear Information System (INIS)

    Merrick, H.W.; Dobelbower, R.R.; Ringleint, J.F.; Skeel, R.T.

    1986-01-01

    Renewed interest in hepatic artery infusion has been stimulated by the development of a totally implantable pump which eliminates many of the problems encountered by the external pumps and catheters. As the potential benefit of hepatic artery infusion would be greater if either all gross disease were removed by prior resection, or alternatively, if non-resectable disease were irradiated in conjunction with hepatic artery infusion, the authors initiated a phase I-II trial to evaluate combined modality therapy

  19. Development of extrahepatic arterial blood supply to the liver during hepatic arterial infusion chemotherapy

    International Nuclear Information System (INIS)

    Seki, H.; Kimura, M.; Yoshimura, N.; Yamamoto, S.; Ozaki, T.; Sakai, K.

    1998-01-01

    The aim of this study was to evaluate the correlation of development of the collateral circulation to the liver during hepatic arterial infusion chemotherapy (HAIC) with the presence of hepatic tumours adjacent to the hepatic surface, and with pretreatment occlusion of aberrant hepatic arteries. In 102 patients with unresectable malignant hepatic tumours treated with HAIC using an implantable port system, development of collaterals to the liver was assessed with CT arteriography using the implantable port and pre- and postoperative angiography. Aberrant hepatic arteries, if present, were occluded prior to treatment for hepatic arterial redistribution. Collaterals to the liver were seen in 29 patients, who had 35 areas with collateral perfusion: 22 areas were in the right posterosuperior area, 6 in the left peripheral area and 7 in the right or left lobar area. Collaterals were revealed more frequently in patients with hepatic tumours adjacent to the hepatic surface than in those without hepatic tumours in peripheral areas in the liver (p < 0.0001). In addition, collaterals developed more frequently in patients with an aberrant hepatic arterial anatomy compared with those with conventional anatomy (p = 0.0007). Our results indicated that patients with hepatic tumours adjacent to the hepatic surface and with pretreatment occlusion of aberrant hepatic arteries had the potential to develop collaterals to the liver during HAIC. (orig.)

  20. Preventing hepatitis B or C

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000401.htm Preventing hepatitis B or C To use the sharing features on this page, please enable JavaScript. Hepatitis B and hepatitis C infections cause irritation and ...

  1. Hepatitis in the United States

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. John Ward, Director of CDC’s Division of Viral Hepatitis, discusses the different types of viral hepatitis and how they can be prevented. He also describes how hepatitis is transmitted and treated.

  2. Primary isolated hepatic tuberculosis

    International Nuclear Information System (INIS)

    Sheikh, A.S.F.; Qureshi, I.H.; Saba, K.; Bukhari, M.H.

    2013-01-01

    Isolated hepatic tuberculosis without pulmonary or bowel involvement is a diagnostic challenge and can cause considerable morbidity. A young lady from Lahore presented with fever, pain in right hypochondria, nausea and weight loss. CT scan of abdomen showed multiple small hypodense non-enhancing lesions and a heterogeneous texture of liver. Biopsy confirmed the diagnosis of hepatic tuberculosis. It was concluded a case of isolated hepatic tuberculosis without evidence of other primary sites involvement. It is important to consider tuberculosis in the differential diagnosis when suspecting lymphoproliferative or metastatic diseases in a patient with vague symptoms and abnormal hepatic texture on CT. (author)

  3. Hepatitis A virus antibody

    International Nuclear Information System (INIS)

    Novak, J.; Kselikova, M.; Urbankova, J.

    1980-01-01

    A description is presented of a radioimmunoassay designed to prove the presence of the antibody against the hepatitis A virus (HA Ab, anti-Ha) using an Abbott HAVAB set. This proof as well as the proof of the antibody against the nucleus of the hepatitis B virus is based on competition between a normal antibody against hepatitis A virus and a 125 I-labelled antibody for the binding sites of a specific antigen spread all over the surface of a tiny ball; this is then indirect proof of the antibody under investigation. The method is described of reading the results from the number of impulses per 60 seconds: the higher the titre of the antibody against the hepatitis A virus in the serum examined, the lower the activity of the specimen concerned. The rate is reported of incidence of the antibody against the hepatitis A virus in a total of 68 convalescents after hepatitis A; the antibody was found in 94.1%. The immunoglobulin made from the convalescents' plasma showed the presence of antibodies in dilutions as high as 1:250 000 while the comparable ratio for normal immunoglobulin Norga was only 1:2500. Differences are discussed in the time incidence of the antibodies against the hepatitis A virus, the antibodies against the surface antigen of hepatitis B, and the antibody against the nucleus of the hepatitis V virus. (author)

  4. Hepatic crown-like structure: a unique histological feature in non-alcoholic steatohepatitis in mice and humans.

    Directory of Open Access Journals (Sweden)

    Michiko Itoh

    Full Text Available Although macrophages are thought to be crucial for the pathogenesis of chronic inflammatory diseases, how they are involved in disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH is poorly understood. Here we report the unique histological structure termed "hepatic crown-like structures (hCLS" in the mouse model of human NASH; melanocortin-4 receptor deficient mice fed a Western diet. In hCLS, CD11c-positive macrophages aggregate to surround hepatocytes with large lipid droplets, which is similar to those described in obese adipose tissue. Histological analysis revealed that hCLS is closely associated with activated fibroblasts and collagen deposition. When treatment with clodronate liposomes effectively depletes macrophages scattered in the liver, with those in hCLS intact, hepatic expression of inflammatory and fibrogenic genes is unaffected, suggesting that hCLS is an important source of inflammation and fibrosis during the progression of NASH. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. We also observed increased number of hCLS in the liver of non-alcoholic fatty liver disease/NASH patients. Collectively, our data provide evidence that hCLS is involved in the development of hepatic inflammation and fibrosis, thereby suggesting its pathophysiologic role in disease progression from simple steatosis to NASH.

  5. CHRONIC HEPATITIS OR «DISGUISE» PAROXYSMAL NOCTURAL HEMOGLOBINURIA?

    Directory of Open Access Journals (Sweden)

    D. A. Dolgopolova

    2015-01-01

    Full Text Available Objective is description of a case of diagnostics of a paroxysmal nocturnal haemoglobinuria. Subjects and methods. The male patient of 50 years asked for medical care with complaints to emergence of yellowness a skin, urine darkening, not expressed general weakness. To the patient examination was conducted: clinical and biochemical blood tests, urine, miyelogramm, definition of an index of sphericity of erythrocytes, definition of free hemoglobin of plasma of blood, urine, gemosiderinuriya, flow citometry, immunological markers of rheumatic diseases, tool inspection, etc. Results. On the basis of complaints, a clinical picture of a disease, data of objective and tool inspections the final diagnosis is made: a paroxysmal nocturnal haemoglobinuria, a classical haemolytic form (on the International classification of diseases of the 10th revision – B 59.5. The comorbid diagnoses: anemia of heavy degree; transfusion dependence; thrombosis of a subclavial vein on the right (11.2011; cholelithiasis; chronic calculous cholecystitis in remission; chronic hepatitis of the mixed genesis (alcoholic, metabolic, moderate degree of activity. By the main diagnostic method which allowed to verify the diagnosis became flow citometry. According to an flow citometry erythrocytes I Tip (normal expression of CD59 – 87,0 %, II Type (partial deficiency of CD59 – 0,3 %, III Type (full deficiency of CD59 – 12,7 %; monocytes with deficiency of FLAER/CD14 – 93,3 %; granulocytes with deficiency of FLAER/CD24 – 97,7 %. Flow citometry was revealed by availability of APG-clone among erythrocytes, granulocytes and monocytes. Judging by the huge size of a clone (on granulocytes 97,7 %, it is possible to draw a conclusion that the patient was in the highest zone of risk of APG of crises. Conclusion. Practical interest of this supervision is caused by a rarity of this hematologic disease, the analysis of modern opportunities of diagnostics and complexity of a choice of

  6. Muscle phosphoglycerate mutase deficiency revisited

    DEFF Research Database (Denmark)

    Naini, Ali; Toscano, Antonio; Musumeci, Olimpia

    2009-01-01

    storage disease type X and novel mutations in the gene encoding the muscle subunit of PGAM (PGAM2). DESIGN: Clinical, pathological, biochemical, and molecular analyses. SETTING: Tertiary care university hospitals and academic institutions. Patients A 37-year-old Danish man of Pakistani origin who had...... PGAM deficiency, and molecular studies revealed 2 novel homozygous mutations, a nonsense mutation and a single nucleotide deletion. Pathological studies of muscle showed mild glycogen accumulation but prominent tubular aggregates in both patients. CONCLUSIONS: We found that glycogen storage disease...

  7. Acute metabolic decompensation due to influenza in a mouse model of ornithine transcarbamylase deficiency

    Directory of Open Access Journals (Sweden)

    Peter J. McGuire

    2014-02-01

    Full Text Available The urea cycle functions to incorporate ammonia, generated by normal metabolism, into urea. Urea cycle disorders (UCDs are caused by loss of function in any of the enzymes responsible for ureagenesis, and are characterized by life-threatening episodes of acute metabolic decompensation with hyperammonemia (HA. A prospective analysis of interim HA events in a cohort of individuals with ornithine transcarbamylase (OTC deficiency, the most common UCD, revealed that intercurrent infection was the most common precipitant of acute HA and was associated with markers of increased morbidity when compared with other precipitants. To further understand these clinical observations, we developed a model system of metabolic decompensation with HA triggered by viral infection (PR8 influenza using spf-ash mice, a model of OTC deficiency. Both wild-type (WT and spf-ash mice displayed similar cytokine profiles and lung viral titers in response to PR8 influenza infection. During infection, spf-ash mice displayed an increase in liver transaminases, suggesting a hepatic sensitivity to the inflammatory response and an altered hepatic immune response. Despite having no visible pathological changes by histology, WT and spf-ash mice had reduced CPS1 and OTC enzyme activities, and, unlike WT, spf-ash mice failed to increase ureagenesis. Depression of urea cycle function was seen in liver amino acid analysis, with reductions seen in aspartate, ornithine and arginine during infection. In conclusion, we developed a model system of acute metabolic decompensation due to infection in a mouse model of a UCD. In addition, we have identified metabolic perturbations during infection in the spf-ash mice, including a reduction of urea cycle intermediates. This model of acute metabolic decompensation with HA due to infection in UCD serves as a platform for exploring biochemical perturbations and the efficacy of treatments, and could be adapted to explore acute decompensation in other

  8. Impaired LDL receptor-related protein 1 translocation correlates with improved dyslipidemia and atherosclerosis in apoE-deficient mice.

    Directory of Open Access Journals (Sweden)

    Philip L S M Gordts

    Full Text Available OBJECTIVE: Determination of the in vivo significance of LDL receptor-related protein 1 (LRP1 dysfunction on lipid metabolism and atherosclerosis development in absence of its main ligand apoE. METHODS AND RESULTS: LRP1 knock-in mice carrying an inactivating mutation in the NPxYxxL motif were crossed with apoE-deficient mice. In the absence of apoE, relative to LRP1 wild-type animals, LRP1 mutated mice showed an increased clearance of postprandial lipids despite a compromised LRP1 endocytosis rate and inefficient insulin-mediated translocation of the receptor to the plasma membrane, likely due to inefficient slow recycling of the mutated receptor. Postprandial lipoprotein improvement was explained by increased hepatic clearance of triglyceride-rich remnant lipoproteins and accompanied by a compensatory 1.6-fold upregulation of LDLR expression in hepatocytes. One year-old apoE-deficient mice having the dysfunctional LRP1 revealed a 3-fold decrease in spontaneous atherosclerosis development and a 2-fold reduction in LDL-cholesterol levels. CONCLUSION: These findings demonstrate that the NPxYxxL motif in LRP1 is important for insulin-mediated translocation and slow perinuclear endosomal recycling. These LRP1 impairments correlated with reduced atherogenesis and cholesterol levels in apoE-deficient mice, likely via compensatory LDLR upregulation.

  9. Hepatic Rupture Induced by Spontaneous Intrahepatic Hematoma

    Directory of Open Access Journals (Sweden)

    Jin-bao Zhou

    2018-01-01

    Full Text Available The etiology of hepatic rupture is usually secondary to trauma, and hepatic rupture induced by spontaneous intrahepatic hematoma is clinically rare. We describe here a 61-year-old female patient who was transferred to our hospital with hepatic rupture induced by spontaneous intrahepatic hematoma. The patient had no history of trauma and had a history of systemic lupus erythematosus for five years, taking a daily dose of 5 mg prednisone for treatment. The patients experienced durative blunt acute right upper abdominal pain one day after satiation, which aggravated in two hours, accompanied by dizziness and sweating. Preoperative diagnosis was rupture of the liver mass. Laparotomy revealed 2500 mL fluid consisting of a mixture of blood and clot in the peritoneal cavity. A 3.5 cm × 2.5 cm rupture was discovered on the hepatic caudate lobe near the vena cava with active arterial bleeding, and a 5  × 6 cm hematoma was reached on the right posterior lobe of the liver. Abdominal computed tomography (CT and laparotomy revealed spontaneous rupture of intrahepatic hematoma with hemorrhagic shock. The patient was successfully managed by suturing the rupture of the hepatic caudate lobe and clearing part of the hematoma. The postoperative course was uneventful, and the patient was discharged after two weeks of hospitalization.

  10. Hepatic JAK2 protects against atherosclerosis through circulating IGF-1.

    Science.gov (United States)

    Sivasubramaniyam, Tharini; Schroer, Stephanie A; Li, Angela; Luk, Cynthia T; Shi, Sally Yu; Besla, Rickvinder; Dodington, David W; Metherel, Adam H; Kitson, Alex P; Brunt, Jara J; Lopes, Joshua; Wagner, Kay-Uwe; Bazinet, Richard P; Bendeck, Michelle P; Robbins, Clinton S; Woo, Minna

    2017-07-20

    Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown. We show here that hepatic Jak2 deficiency in atherosclerosis-prone mouse models exhibited accelerated atherosclerosis with increased plaque macrophages and decreased plaque smooth muscle cell content. JAK2's essential role in growth hormone signalling in liver that resulted in reduced IGF-1 with hepatic Jak2 deficiency played a causal role in exacerbating atherosclerosis. As such, restoring IGF-1 either pharmacologically or genetically attenuated atherosclerotic burden. Together, our data show hepatic Jak2 to play a protective role in atherogenesis through actions mediated by circulating IGF-1 and, to our knowledge, provide a novel liver-centric mechanism in atheroprotection.

  11. Cobalamin deficiency, hyperhomocysteinemia, and dementia

    Directory of Open Access Journals (Sweden)

    Steven F Werder

    2010-04-01

    Full Text Available Steven F Werder1,21Kansas University School of Medicine – Wichita, Wichita, KS, USA; 2Community Health Center of Southeast Kansas, Pittsburg, KS, USAIntroduction: Although consensus guidelines recommend checking serum B12 in patients with dementia, clinicians are often faced with various questions: (1 Which patients should be tested? (2 What test should be ordered? (3 How are inferences made from such testing? (4 In addition to serum B12, should other tests be ordered? (5 Is B12 deficiency compatible with dementia of the Alzheimer’s type? (6 What is to be expected from treatment? (7 How is B12 deficiency treated?Methods: On January 31st, 2009, a Medline search was performed revealing 1,627 citations related to cobalamin deficiency, hyperhomocysteinemia, and dementia. After limiting the search terms, all abstracts and/or articles and other references were categorized into six major groups (general, biochemistry, manifestations, associations and risks, evaluation, and treatment and then reviewed in answering the above questions.Results: The six major groups above are described in detail. Seventy-five key studies, series, and clinical trials were identified. Evidence-based suggestions for patient management were developed.Discussion: Evidence is convincing that hyperhomocysteinemia, with or without hypovitaminosis B12, is a risk factor for dementia. In the absence of hyperhomocysteinemia, evidence is less convincing that hypovitaminosis B12 is a risk factor for dementia. B12 deficiency manifestations are variable and include abnormal psychiatric, neurological, gastrointestinal, and hematological findings. Radiological images of individuals with hyperhomocysteinemia frequently demonstrate leukoaraiosis. Assessing serum B12 and treatment of B12 deficiency is crucial for those cases in which pernicious anemia is suspected and may be useful for mild cognitive impairment and mild to moderate dementia. The serum B12 level is the standard initial test

  12. Hepatitis E as a Zoonosis.

    Science.gov (United States)

    Widén, Frederik

    2016-01-01

    Hepatitis E (HE) virus infection is not limited to spread from human to human but also occurs between animals and more importantly as zoonotic spread from animals to humans. Genotyping of strains from hepatitis E virus-infected patients has revealed that these infections are not all caused by genotypes 1 or 2 but often by genotypes 3 or 4. Therefore, it is important to understand the striking difference between the spread of genotypes 1 and 2 in countries with poor sanitary standards and the spread of genotypes 3 and 4 in countries with good sanitary standards. The number of animal species known to be infected with HEV is expanding rapidly. The finding of HEV in new host species always raises the question regarding the zoonotic potential of these newfound strains. However, as new strains are found, the complexity increases.Certain genotypes are known to have the ability of zoonotic spread from certain animal species and these animals may even constitute an infection reservoir. Some animal species may contribute to zoonotic infections albeit on a smaller scale, while others are believed to be of minor or no importance at all. This chapter reviews possible sources of zoonotic hepatitis E virus infection.

  13. Hypercalcemia due to Primary Hepatic Lymphoma

    Directory of Open Access Journals (Sweden)

    Andrew Hsu

    2016-01-01

    Full Text Available A 65-year-old female with a history of mixed connective tissue disease and pulmonary fibrosis on azathioprine, hydroxychloroquine, and prednisone (osteoporosis on teriparatide presented with a 1-month history of hypercalcemia. After discontinuation of teriparatide, the patient’s hypercalcemia persisted. Further evaluation revealed primary hepatic lymphoma as the source of her hypercalcemia.

  14. Fine-needle aspirate cytology suggesting hepatic lipidosis in four cats with infiltrative hepatic disease.

    Science.gov (United States)

    Willard, M D; Weeks, B R; Johnson, M

    1999-12-01

    Four cats are reported in which cytology smears obtained by ultrasound-guided fine needle aspiration of the liver were interpreted as indicative of hepatic lipidosis. However, histopathology of hepatic tissue samples obtained with Tru-Cut-like needles or wedge biopsy revealed that the cats had inflammatory or neoplastic hepatic disease causing their clinical signs. Fine needle aspiration and cytology may not detect infiltrative lesions, particularly those that are nodular, multifocal, or localised around the portal regions. Fine needle aspirate cytology is a useful diagnostic procedure with many advantages, but care must be taken to avoid diagnosing hepatic lipidosis as the cause of illness when an infiltrative lesion is responsible. Copyright 1999 European Society of Feline Medicine.

  15. Vitamin B12 deficiency

    DEFF Research Database (Denmark)

    Green, Ralph; Allen, Lindsay H; Bjørke-Monsen, Anne-Lise

    2017-01-01

    , subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals. Infants, children, adolescents and women of reproductive age...... remain debated. Management depends on B12 supplementation, either via high-dose oral routes or via parenteral administration. This Primer describes the current knowledge surrounding B12 deficiency, and highlights improvements in diagnostic methods as well as shifting concepts about the prevalence, causes...

  16. Loss of miR-141/200c ameliorates hepatic steatosis and inflammation by reprogramming multiple signaling pathways in NASH

    Science.gov (United States)

    Tran, Melanie; Lee, Sang-Min; Shin, Dong-Ju

    2017-01-01

    Accumulation of lipid droplets and inflammatory cell infiltration is the hallmark of nonalcoholic steatohepatitis (NASH). The roles of noncoding RNAs in NASH are less known. We aim to elucidate the function of miR-141/200c in diet-induced NASH. WT and miR-141/200c–/– mice were fed a methionine and choline deficient (MCD) diet for 2 weeks to assess markers of steatosis, liver injury, and inflammation. Hepatic miR-141 and miR-200c RNA levels were highly induced in human patients with NASH fatty liver and in WT MCD mice. miR-141/200c–/– MCD mice had reduced liver weights and triglyceride (TG) levels, which was associated with increased microsomal TG transfer protein (MTTP) and PPARα but reduced SREBP1c and FAS expression. Inflammation was attenuated and F4/80 macrophage activation was suppressed in miR-141/200c–/– mice, as evidenced by decreased serum aminotransferases and IL-6 and reduced hepatic proinflammatory, neutrophil, and profibrotic genes. Treatment with LPS in BM-derived macrophages isolated from miR-200c/141–/– mice polarized macrophages toward the M2 antiinflammatory state by increasing Arg1 and IL-10 levels while decreasing the M1 marker iNOS. In addition, elevated phosphorylated AMPK (p-AMPK), p-AKT, and p-GSK3β and diminished TLR4 and p-mTOR/p-4EBP1 proteins were observed. Lipidomics and metabolomics revealed alterations of TG and phosphatidylcholine (PC) lipid species by miR-141/200c deficiency. In summary, miR-141/200c deficiency diminished NASH-associated hepatic steatosis and inflammation by reprogramming lipid and inflammation signaling pathways. PMID:29093267

  17. [Immunological status of patients with amebic hepatic abscess].

    Science.gov (United States)

    Canto Solís, A; Miranda Feria, A J; Medina Martinez, J; Teran Ortíz, L A; Suárez Sánchez, F

    1975-01-01

    The authors studied 10 cases of amoebic hepatic abscess documented by clinical evidence and confirmed by laboratory tests, liver scan and a good response to treatment. The immunological state of the patients was determined by protein electrophoresis, immunoelectrophoresis, counter-immunoelectrophoresis, radial immunodiffusion and roset formation for T and B lymphocytes. It is concluded that the alterations of cellular and humoral immunity is evident in cases of amoebic hepatic abscess; this alterations are more clear in the acute form of the illness and the immunological deficiency is more significant in the celular immunity.

  18. Diabetes and hepatitis C : A two-way association

    Directory of Open Access Journals (Sweden)

    Sara Salehi Hammerstad

    2015-09-01

    Full Text Available Diabetes and hepatitis C infection are both prevalent diseases worldwide, and are associated with increased morbidity and mortality. Most studies, but not all, have shown that patients with chronic hepatitis C are more prone to develop type 2 diabetes compared to healthy controls, as well as when compared to patients with other liver diseases including hepatitis B. Furthermore, epidemiological studies have revealed that patients with type 2 diabetes may also be at higher risk for worse outcomes of their hepatitis C infection, including reduced rate of sustained virologic response, progression to fibrosis and cirrhosis, and higher risk for development of hepatocellular carcinoma. Moreover, hepatitis C infection and mainly its treatment, interferon α, can trigger the development of type 1 diabetes. In this review we discuss the existing data on this two-way association between diabetes and hepatitis C infection with emphasis on possible mechanisms. It remains to be determined whether the new curative therapies for chronic hepatitis C will improve outcomes in diabetic hepatitis C patients, and conversely whether treatment with Metformin will reduce complications from HCV infection. We propose an algorithm for diabetes screening and follow-up in hepatitis C patients.

  19. An Adolescent Case of Citrin Deficiency With Severe Anorexia Mimicking Anorexia Nervosa.

    Science.gov (United States)

    Takeuchi, Satsuki; Yazaki, Masahide; Yamada, Shinji; Fukuyama, Tetsuhiro; Inui, Akio; Iwasaki, Yasushi; Ikeda, Shu-ichi

    2015-08-01

    We report a 12-year-old female citrin-deficient patient presenting with severe anorexia and body weight loss, mimicking the restricting type of anorexia nervosa (AN). She showed normal development until age 10 years when she started to play volleyball at school. She then became gradually anorexic, and her growth was stunted. At age 12, she was admitted to hospital because of severe anorexia and thinness. She was first thought to have AN, and drip infusion of glucose solution and high-calorie drinks were given, but her condition deteriorated further. She had a history of neonatal hepatitis and was therefore suspected to have citrin deficiency (CD). Genetic analysis of SLC25A13 revealed that she was compound heterozygous for 851del4 and IVS16ins3kb, and a diagnosis of CD was made. A low-carbohydrate diet with oral intake of arginine and ursodeoxycholic acid was started, and her condition gradually improved. The clinical features in our patient were similar to those of AN, and therefore AN may also be an important clinical sign in adolescent patients with CD. Copyright © 2015 by the American Academy of Pediatrics.

  20. The hepatic bridge.

    Science.gov (United States)

    Sugarbaker, Paul H

    2018-07-01

    The hepatic bridge forms a tunnel of liver parenchyma that may obscure peritoneal metastases associated with the round ligament. Visualization and then resection of nodules associated with this structure is necessary. The incidence of a hepatic bridge and the extent that it covered the round ligament was determined in consecutive patients. Extent of coverage of the round ligament by the hepatic bridge was determined: Class 1 indicates up to one-third of the round ligament obscured, Class 2 up to two-thirds and Class 3 more than two-thirds. In 102 patients in whom the round ligament of the liver could be completely visualized, 50 had a hepatic bridge. Class 1 was 22 (44%) of the bridges, Class 2 was 16 (32%) and Class 3 was 12 (24%). A hepatic bridge was more frequently present in 28 of 45 male patients (62%) vs. 22 of 57 female patients (38%). Approximately one-half of our patients having cytoreductive surgery for peritoneal metastases were observed to have a hepatic bridge. Up to 56% of these patients have Class 2 or 3 hepatic bridge and may require division of the hepatic bridge to completely visualize the contents of the tunnel created by this structure. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  1. Hepatitis C Test

    Science.gov (United States)

    ... and Prevention. Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945–1965. Prepared by ... Disease Control and Prevention. Vital Signs: Evaluation of Hepatitis C Virus Infection Testing and Reporting — Eight U.S. Sites, 2005–2011. ...

  2. Cytomegalovirus Hepatitis During Pregnancy

    Directory of Open Access Journals (Sweden)

    Ying Chan

    1995-01-01

    Full Text Available Background: Although cytomegalovirus (CMV is an uncommon cause of viral hepatitis during pregnancy, a definitive diagnosis is important because of the potential for congenital CMV. In the case reported here, a diagnosis of hepatitis caused by CMV was made after the more common viral pathogens had been ruled out.

  3. Hepatitis E og graviditet

    DEFF Research Database (Denmark)

    Mannheimer, Ebba Elisabeth; Harritshøj, Lene Holm; Katzenstein, Terese Lea

    2016-01-01

    Hepatitis E virus (HEV) infection among pregnant women is severe, often leading to fulminant hepatic failure and death, with mortality rates up to 15-25%. Studies suggest that differences in genotypes/subgenotypes, hormonal and immunological changes during pregnancy may contribute to the severe...

  4. Glucose-6-phosphate dehydrogenase deficiency in Singapore.

    Science.gov (United States)

    Quak, S H; Saha, N; Tay, J S

    1996-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) in man is an X-linked enzyme. The deficiency of this enzyme is one of the most common inherited metabolic disorders in man. In Singapore, three clinical syndromes associated with G6PD deficiency had been described: severe haemolysis in neonates with kernicterus, haemoglobinuria and "viral hepatitis"-like syndrome. The human G6PD monomer consists of 515 amino acids. Only the tetrameric or dimeric forms composed of a single type subunit are catylitically active. The complete amino acid sequence of G6PD had been elucidated in man and various other animals. The region of high homology among the enzymes of various animals is presumably functionally active. Among the Chinese in Singapore, three common molecular variants had been identified: Canton (nt 1376 G --> T), Kaiping (nt 1388 G --> A) and Mediterranean (nt 563 C --> T) in frequencies of 24%, 21% and 10% respectively. In addition, two common mutants (Gaozhou, nt 95 A --> G and Chinese 5, nt 1024 C --> T) have been detected in Singapore Chinese in low frequencies. In Malays, 6 different deficient variants are known in Singapore (3 new, 1 Mahidol, 1 Indonesian and 1 Mediterranean).

  5. Pentoxifylline for alcoholic hepatitis

    DEFF Research Database (Denmark)

    Whitfield, Kate; Rambaldi, Andrea; Wetterslev, Jørn

    2009-01-01

    BACKGROUND: Alcoholic hepatitis is a life-threatening disease, with an average mortality of approximately 40%. There is no widely accepted, effective treatment for alcoholic hepatitis. Pentoxifylline is used to treat alcoholic hepatitis, but there has been no systematic review to assess its effects....... OBJECTIVES: To assess the benefits and harms of pentoxifylline in alcoholic hepatitis. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, LILACS......, clinicaltrials.gov, and full text searches were conducted until August 2009. Manufacturers and authors were contacted. SELECTION CRITERIA: All randomised clinical trials of pentoxifylline in participants with alcoholic hepatitis compared to control were selected for inclusion. DATA COLLECTION AND ANALYSIS: Two...

  6. Serum Hepatitis C virus and hepatitis B surface antigenaemia in ...

    African Journals Online (AJOL)

    Acute hepatitis is common in Nigeria and hepatitis B virus (HBV) infection has been a major aetiological factor. However, the role of Hepatitis C virus (HCV) infection is yet undetermined. Forty-five consecutive Nigerian patients with acute Icteric hepatitis (AIH) attending the Medical Clinic of the University College Hospital, ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... body to absorb iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, you ... to iron-deficiency anemia include: Bleeding in your GI tract, from an ulcer, colon cancer, or regular ...

  8. Iron-Deficiency Anemia

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  10. Iron-Deficiency Anemia

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  11. Iron-Deficiency Anemia

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    Full Text Available ... our clinical trials . Are you a frequent blood donor living in New York City? This study is looking at how iron-deficiency anemia in blood donors affects the quality of donated red blood cells, ...

  12. Vitamin D Deficiency

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    ... to other diseases. In children, it can cause rickets. Rickets is a rare disease that causes the bones ... and children are at higher risk of getting rickets. In adults, severe vitamin D deficiency leads to ...

  13. Iron-Deficiency Anemia

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  17. Iron-Deficiency Anemia

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  18. Iron-Deficiency Anemia

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  19. Iron-Deficiency Anemia

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    Full Text Available ... red blood cells, called hemolysis . Hemolysis, in this case, is caused by strong muscle contractions and the ... to prevent iron-deficiency anemia. Participate in NHLBI Clinical Trials will explain our ongoing clinical studies that ...

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  1. Iron-Deficiency Anemia

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    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness ... If your doctor diagnoses you with iron-deficiency anemia, your treatment will depend on the cause and severity of the condition. Your ...

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    Full Text Available ... heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, such as ... iron-deficiency anemia may require intravenous (IV) iron therapy or a blood transfusion . Iron supplements Your doctor ...

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  11. Factor V deficiency

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    ... this page: //medlineplus.gov/ency/article/000550.htm Factor V deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  12. Factor II deficiency

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    ... this page: //medlineplus.gov/ency/article/000549.htm Factor II deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  13. Factor X deficiency

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    ... this page: //medlineplus.gov/ency/article/000553.htm Factor X deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  14. Iron-Deficiency Anemia

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  15. Iron-Deficiency Anemia

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  16. Iron-Deficiency Anemia

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  17. Iron-Deficiency Anemia

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  18. Iron-Deficiency Anemia

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  20. Iron-Deficiency Anemia

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    Full Text Available ... may recommend erythropoiesis stimulating agents (esa) . These medicines stimulate the bone marrow to make more red blood ... NHLBI is funding on iron-deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision ...