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Sample records for delta hepatitis molecular

  1. Delta hepatitis: molecular biology and clinical and epidemiological features.

    PubMed Central

    Polish, L B; Gallagher, M; Fields, H A; Hadler, S C

    1993-01-01

    Hepatitis delta virus, discovered in 1977, requires the help of hepatitis B virus to replicate in hepatocytes and is an important cause of acute, fulminant, and chronic liver disease in many regions of the world. Because of the helper function of hepatitis delta virus, infection with it occurs either as a coinfection with hepatitis B or as a superinfection of a carrier of hepatitis B surface antigen. Although the mechanisms of transmission are similar to those of hepatitis B virus, the patterns of transmission of delta virus vary widely around the world. In regions of the world in which hepatitis delta virus infection is not endemic, the disease is confined to groups at high risk of acquiring hepatitis B infection and high-risk hepatitis B carriers. Because of the propensity of this viral infection to cause fulminant as well as chronic liver disease, continued incursion of hepatitis delta virus into areas of the world where persistent hepatitis B infection is endemic will have serious implications. Prevention depends on the widespread use of hepatitis B vaccine. This review focuses on the molecular biology and the clinical and epidemiologic features of this important viral infection. PMID:8358704

  2. Delta agent (Hepatitis D)

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000216.htm Delta agent (Hepatitis D) To use the sharing features on this page, please enable JavaScript. Delta agent is a type of virus called hepatitis ...

  3. Delta hepatitis in Malaysia.

    PubMed

    Sinniah, M; Dimitrakakis, M; Tan, D S

    1986-06-01

    Sera from one hundred and fifty nine Malaysian individuals were screened for the prevalence of delta markers. These included 15 HBsAg positive homosexuals, 16 acute hepatitis B cases, 9 chronic hepatitis B patients, 13 healthy HBsAg carriers and 106 intravenous (i.v.) drug abusers, of whom 27 were positive for HBsAg only and the rest were anti-HBc IgG positive but HBsAg negative. The prevalence of delta markers in the homosexuals was found to be 6.7%, in the HBsAg positive drug abusers 17.8%, in acute hepatitis B cases 12.5%. No evidence of delta infection was detected in healthy HBsAg carriers, chronic hepatitis B cases and HBsAg negative i.v. drug abusers. With reference to i.v. drug abusers, the prevalence of delta markers was higher in Malays (23%) than in Chinese (7%) although the latter had a higher HBsAg carrier rate. Although the HBsAg carrier rate in the homosexuals was high, their delta prevalence rate was low as compared to drug abusers. In Malaysia, as in other non-endemic regions, hepatitis delta virus transmission appeared to occur mainly via the parenteral and sexual routes. This is the first time in Malaysia that a reservoir of delta infection has been demonstrated in certain groups of the population at high risk for hepatitis B.

  4. Epidemiological and molecular features of hepatitis B and hepatitis delta virus transmission in a remote rural community in central Africa.

    PubMed

    François-Souquière, Sandrine; Makuwa, Maria; Bisvigou, Ulrich; Kazanji, Mirdad

    2016-04-01

    Hepatitis B virus (HBV) and hepatitis delta virus (HDV) occur worldwide and are prevalent in both urban and remote rural communities. In a remote village in Gabon, central Africa, we observed a high prevalence of HBsAg carriage and HDV infection, particularly in children and adolescents. The prevalence of HBsAg differed significantly by gender and age, females being more likely than males to carry the HBsAg during the first 10 years of life, while the prevalence was higher among males than females aged 11-20 years. We also characterised HBV and HDV strains circulating in the village. The principal HBV strains belonged to genotype HBV-E and subgenotype QS-A3. Complete genome analysis revealed for the first time the presence of the HBV-D genotype in Gabon, in the form of an HBV-D/E recombinant. Molecular analysis of HDV strains and their complete genomic characterisation revealed two distinct groups within the dominant HDV clade 8. Molecular analysis of HBV and HDV strains did not reveal vertical transmission within the families studied but rather horizontal, intrafamilial transmission among children aged 0-10 years. Our findings indicate that HBV is transmitted in early childhood by body fluids rather than by sexual contact. Health education adapted to the different age groups might therefore help to reduce HBV transmission. Young children should be vaccinated to control HBV infection in areas of extremely high prevalence.

  5. Molecular epidemiology of hepatitis B and hepatitis delta viruses circulating in the Western Amazon region, North Brazil

    PubMed Central

    2014-01-01

    Background Hepatitis B virus (HBV) and hepatitis D virus (HDV) represent important public health problems in the Western Amazon region with reported cases of fulminant hepatitis. This cross sectional study describes HBV and HDV genotypes circulating in the Brazilian Amazon region. Methods HBsAg positive individuals (n = 224) were recruited in Manaus/Amazonas State (130 blood donors from the Hematology and Hemotherapy Foundation from Amazonas/HEMOAM; 60 subjects from outpatient clinic) and in Eirunepe city (n = 34) from 2003–2009. Most participants (n = 153) lived in Manaus, 63 were from 20 remote isolated municipalities, 8 lived outside Amazonas State. Genotyping was based on PCR products: HBV genotype A-F specific primers, restricted length polymorphism for HDV. HDV isolates were directly sequenced (delta antigen 405 nucleotide fragment) and phylogenetic analysis performed (MEGA; neighbor-joining, Kimura’s two parameter). Results Most participants were young adult males and HBV mono-infection predominated (70.5%, 158/224). Among blood donors, outpatient subjects and individuals from Eirunepe, HBV/A prevailed followed by HBV/D and F (p > 0.05). HBV/A was more frequent in blood donors (p < 0.05). HBV-HDV coinfection rate was 8.5% in blood donors (11/130), 65.0% (39/60) in outpatient subjects and 47.0% (16/34) in individuals from Eirunepe. Compared to blood donors, coinfection was higher in outpatient subjects (65.0% versus 8.5%; RR = 5.0; CI 3.4-7.9; p < 0.0001) and in subjects from Eirunepe (47.0% versus 8.5%; RR = 5.5; CI 3.0-9.9; p < 0.0001). HBV-HDV coinfection rates were higher in patients from highly endemic remote cities. Only HDV genotype 3 was detected, HBV/F-HDV/3 predominated (20/38; 52.7%), followed by HBV/A-HDV/3 (31.6%; 12/38) and HBV/D-HDV/3 (15.8%; 6/38). Conclusions The description of HBV and HDV genotypes circulating in the western Amazon can contribute to a better understanding of their relevance on the

  6. Whole-genome analysis of genetic recombination of hepatitis delta virus: molecular domain in delta antigen determining trans-activating efficiency.

    PubMed

    Chao, Mei; Lin, Chia-Chi; Lin, Feng-Ming; Li, Hsin-Pai; Iang, Shan-Bei

    2015-12-01

    Hepatitis delta virus (HDV) is the only animal RNA virus that has an unbranched rod-like genome with ribozyme activity and is replicated by host RNA polymerase. HDV RNA recombination was previously demonstrated in patients and in cultured cells by analysis of a region corresponding to the C terminus of the delta antigen (HDAg), the only viral-encoded protein. Here, a whole-genome recombination map of HDV was constructed using an experimental system in which two HDV-1 sequences were co-transfected into cultured cells and the recombinants were analysed by sequencing of cloned reverse transcription-PCR products. Fifty homologous recombinants with 60 crossovers mapping to 22 junctions were identified from 200 analysed clones. Small HDAg chimeras harbouring a junction newly detected in the recombination map were then constructed. The results further indicated that the genome-replication level of HDV was sensitive to the sixth amino acid within the N-terminal 22 aa of HDAg. Therefore, the recombination map established in this study provided a tool for not only understanding HDV RNA recombination, but also elucidating the related mechanisms, such as molecular elements responsible for the trans-activation levels of the small HDAg.

  7. Quantum Mechanical/Molecular Mechanical Free Energy Simulations of the Self-Cleavage Reaction in the Hepatitis Delta Virus Ribozyme

    PubMed Central

    2015-01-01

    The hepatitis delta virus (HDV) ribozyme catalyzes a self-cleavage reaction using a combination of nucleobase and metal ion catalysis. Both divalent and monovalent ions can catalyze this reaction, although the rate is slower with monovalent ions alone. Herein, we use quantum mechanical/molecular mechanical (QM/MM) free energy simulations to investigate the mechanism of this ribozyme and to elucidate the roles of the catalytic metal ion. With Mg2+ at the catalytic site, the self-cleavage mechanism is observed to be concerted with a phosphorane-like transition state and a free energy barrier of ∼13 kcal/mol, consistent with free energy barrier values extrapolated from experimental studies. With Na+ at the catalytic site, the mechanism is observed to be sequential, passing through a phosphorane intermediate, with free energy barriers of 2–4 kcal/mol for both steps; moreover, proton transfer from the exocyclic amine of protonated C75 to the nonbridging oxygen of the scissile phosphate occurs to stabilize the phosphorane intermediate in the sequential mechanism. To explain the slower rate observed experimentally with monovalent ions, we hypothesize that the activation of the O2′ nucleophile by deprotonation and orientation is less favorable with Na+ ions than with Mg2+ ions. To explore this hypothesis, we experimentally measure the pKa of O2′ by kinetic and NMR methods and find it to be lower in the presence of divalent ions rather than only monovalent ions. The combined theoretical and experimental results indicate that the catalytic Mg2+ ion may play three key roles: assisting in the activation of the O2′ nucleophile, acidifying the general acid C75, and stabilizing the nonbridging oxygen to prevent proton transfer to it. PMID:24383543

  8. Substitution rates in hepatitis delta virus.

    PubMed

    Krushkal, J; Li, W H

    1995-12-01

    Substitution rates were estimated for the coding and noncoding regions of the hepatitis delta virus (HDV). The estimated rates of synonymous substitution in HDV were lower than the rates of substitution at non-synonymous sites and in the noncoding region. HDV has lower synonymous substitution rates than the hepatitis C virus, though both are RNA viruses. The relatively low rate of synonymous substitution in HDV may be due to a strong preference of G and C nucleotides at third codon positions. Variation in substitution rate among HDV lineages may be correlated with the clinical development of the HDV-induced hepatitis. The phylogenetic tree inferred for 24 HDV strains reveals similarities between lineages isolated from the same geographic region.

  9. [A study of 158 cases of acute delta hepatitis].

    PubMed

    Castro, A; Buti, M; Esteban, R; Jardí, R; Allende, H; Roget, M; Rodríguez-Frías, F; Guardia, J

    1990-09-22

    We have prospectively studied 158 cases of acute hepatitis delta observed during the last 7 years in a general hospital. Among them 136 were male and 22 female. The mean age was 22.7 years with a range between 16 and 61 years. The epidemiologic factors were drug addiction by parenteral route in 145 cases (92%), sexual transmission in 5 (3%), post transfusional in 2 (1%) and unknown in 6 (4%). With respect to the delta type infection, 105 cases (66%) were coinfections with type B and delta, and 53 patients had a type delta superinfection (34%). The clinical course was a fulminant hepatitis in three cases (two cases of coinfection B and delta an one case of delta superinfection), and an acute benign hepatitis in 155 patients. The follow-up of 118 patients revealed that 96% of coinfections by type B and delta evolved to the chronicity showing findings of active chronic hepatitis or hepatic cirrhosis. It should be noted that in 4 cases of superinfection delta type (11%) the HBsAg was negative after several months of positivity. In these patients the level of transaminases normalized and the hepatic histology evidenced alterations of chronic active hepatitis (2 cases) and hepatic cirrhosis (2 cases) without identification of tissular delta antigen.

  10. High Prevalence and Predominance of Hepatitis Delta Virus Genotype 1 Infection in Cameroon▿

    PubMed Central

    Foupouapouognigni, Yacouba; Noah, Dominique Noah; Sartre, Michèle Tagni; Njouom, Richard

    2011-01-01

    Antibodies to the hepatitis delta virus (HDV) were found in 17.6% of 233 hepatitis B virus surface antigen-positive subjects in Cameroon. Phylogenetic analyses showed the presence of HDV-1, HDV-5, HDV-6, and HDV-7 genotypes. These results enrich the limited data on HDV prevalence and molecular diversity in Cameroon. PMID:21209162

  11. High prevalence and predominance of hepatitis delta virus genotype 1 infection in Cameroon.

    PubMed

    Foupouapouognigni, Yacouba; Noah, Dominique Noah; Sartre, Michèle Tagni; Njouom, Richard

    2011-03-01

    Antibodies to the hepatitis delta virus (HDV) were found in 17.6% of 233 hepatitis B virus surface antigen-positive subjects in Cameroon. Phylogenetic analyses showed the presence of HDV-1, HDV-5, HDV-6, and HDV-7 genotypes. These results enrich the limited data on HDV prevalence and molecular diversity in Cameroon.

  12. Hepatitis B and hepatitis delta virus infection in South America.

    PubMed Central

    Torres, J R

    1996-01-01

    About 100,000 cases of acute hepatitis B virus (HBV) infection occur annually in South America. The overall prevalence of HBV infection in low risk populations ranges from 6.7% to 41%, while hepatitis B surface antigen (HBsAg) rates range from 0.4% to 13%. In high endemicity aboriginal or rural populations, perinatal transmission may play a major part in the spread of HBV. In urban populations, however, horizontal transmission, probably by sexual contact, is the predominant mode of spread, with higher rates of HBV positivity in lower socioeconomic groups. High risk populations such as health care workers and haemodialysis patients show higher rates of HBV infection than comparable populations elsewhere. The risk of posttransfusion hepatitis B remains high in some areas. Concomitant HBV infection may accelerate the chronic liver disease seen in decompensated hepatosplenic schistosomiasis. In the north, the prevalence of hepatitis delta virus (HDV) infection ranks among the highest in the world. In the south, the problem appears negligible although it is increasing within high risk urban communities. HDV superinfection has been the cause of large outbreaks of fulminant hepatitis. The cost of comprehensive or mass vaccination programmes remains unaffordable for most South American countries. Less expensive alternatives such as low dose intradermal schedules of immunisation have been used with success in selected adult subjects. PMID:8786054

  13. Assessment of metal-assisted nucleophile activation in the hepatitis delta virus ribozyme from molecular simulation and 3D-RISM

    PubMed Central

    Radak, Brian K.; Lee, Tai-Sung; Harris, Michael E.

    2015-01-01

    The hepatitis delta virus ribozyme is an efficient catalyst of RNA 2′-O-transphosphorylation and has emerged as a key experimental system for identifying and characterizing fundamental features of RNA catalysis. Recent structural and biochemical data have led to a proposed mechanistic model whereby an active site Mg2+ ion facilitates deprotonation of the O2′ nucleophile, and a protonated cytosine residue (C75) acts as an acid to donate a proton to the O5′ leaving group as noted in a previous study. This model assumes that the active site Mg2+ ion forms an inner-sphere coordination with the O2′ nucleophile and a nonbridging oxygen of the scissile phosphate. These contacts, however, are not fully resolved in the crystal structure, and biochemical data are not able to unambiguously exclude other mechanistic models. In order to explore the feasibility of this model, we exhaustively mapped the free energy surfaces with different active site ion occupancies via quantum mechanical/molecular mechanical (QM/MM) simulations. We further incorporate a three-dimensional reference interaction site model for the solvated ion atmosphere that allows these calculations to consider not only the rate associated with the chemical steps, but also the probability of observing the system in the presumed active state with the Mg2+ ion bound. The QM/MM results predict that a pathway involving metal-assisted nucleophile activation is feasible based on the rate-controlling transition state barrier departing from the presumed metal-bound active state. However, QM/MM results for a similar pathway in the absence of Mg2+ are not consistent with experimental data, suggesting that a structural model in which the crystallographically determined Mg2+ is simply replaced with Na+ is likely incorrect. It should be emphasized, however, that these results hinge upon the assumption of the validity of the presumed Mg2+-bound starting state, which has not yet been definitively verified experimentally

  14. HDVDB: a data warehouse for hepatitis delta virus.

    PubMed

    Singh, Sarita; Gupta, Sunil Kumar; Nischal, Anuradha; Pant, Kamlesh Kumar; Seth, Prahlad Kishore

    2015-01-01

    Hepatitis Delta Virus (HDV) is an RNA virus and causes delta hepatitis in humans. Although a lot of data is available for HDV, but retrieval of information is a complicated task. Current web database 'HDVDB' provides a comprehensive web-resource for HDV. The database is basically concerned with basic information about HDV and disease caused by this virus, genome structure, pathogenesis, epidemiology, symptoms and prevention, etc. Database also supplies sequence data and bibliographic information about HDV. A tool 'siHDV Predict' to design the effective siRNA molecule to control the activity of HDV, is also integrated in database. It is a user friendly information system available at public domain and provides annotated information about HDV for research scholars, scientists, pharma industry people for further study.

  15. Estimation of the secondary attack rate for delta hepatitis coinfection among injection drug users

    PubMed Central

    Poulin, Christiane; Gyorkos, Theresa; Joseph, Lawrence

    1993-01-01

    The secondary attack rate for delta hepatitis coinfection was estimated among a cluster of injection drug users (IDUs). The infections occurred during an epidemic of hepatitis B in a rural area of Nova Scotia in 1988 and 1989. Six IDUs formed a cluster of delta hepatitis coinfections, representing the first reported outbreak of delta hepatitis in Canada. Contact-tracing was used to identify a cluster of 41 IDUs potentially exposed to delta hepatitis. The index case of delta hepatitis coinfection was presumed to have led to five secondary cases. The secondary attack rate was estimated to be 13.2% (95% confidence interval 0.044 to 0.281). The estimated secondary attack rate may be a useful predictor of disease due to delta hepatitis coinfection in similar IDU populations. PMID:22346420

  16. Management of hepatitis delta: Need for novel therapeutic options.

    PubMed

    Abbas, Zaigham; Abbas, Minaam

    2015-08-28

    Hepatitis D virus (HDV) is the smallest single stranded RNA virus infecting humans. The hepatitis B surface antigen envelope protein protects the HDV nucleocapsid antigen and provides a means for the virus to enter and exit the hepatocyte. Hepatitis B and D viruses exploit the human sodium taurocholate co-transporting polypeptide (NTCP), a receptor, for their entry into hepatocytes. Prenylation of the large delta antigen is a critical determinant of HDV particle assembly. Treatment with pegylated interferon results in sustained virological response six months post-treatment in one fourth of the patients. Nucleos(t)ide analogs (NAs) have been widely tested in hepatitis delta, but they appear to be ineffective. Combination treatment of NAs with interferon also proved to be disappointing so there is a need for novel therapeutic options. The receptor function of NTCP is blocked by Myrcludex B, a synthetic N-acylated preS1 lipopeptide that competes with infectious virions for receptor binding. There are already some approved drugs available, including irbesartan, ezetimibe, and ritonavir and cyclosporin A, with documented inhibitory effects on NTCP's metabolic function. These drugs may have a role in HDV treatment. Interference with host-mediated post-translational changes of proteins that are crucial to the HDV life cycle, such as prenylation may become an important tool to control HDV infection and prevent replication. Lonafarnib, a prenylation inhibitor significantly reduces virus levels in hepatitis delta patients. Antisense oligodeoxynucleotides which are complementary to genomic HDV ribozyme self-cleavage site and stem I regions can inhibit genomic HDV ribozyme activity.

  17. Increased serum IgE in acute type A, B and delta hepatitis.

    PubMed

    Gutiérrez, D; Guardia, P; Delgado, J; Gutiérrez, J; Monteseirin, F J; de la Calle, A; Lobatón, P; Senra, A; Conde, J

    1997-01-01

    Serum IgE levels have been documented in patients of acute type B hepatitis. There are very few studies on serum IgE in acute type A hepatitis and, to our knowledge, there are no data on serum IgE in acute delta hepatitis patients. The purpose of this study was to measure total IgE levels in 38 patients with acute A, B and delta hepatitis and in 181 controls in order to determine the possible existence of changes in this parameter in the course of these infections. Our results showed a relevant increase in IgE levels in the three groups (hepatitis A, B and delta) with respect to the control group. Moreover, the hepatitis B group showed increased total serum IgE levels with respect to the hepatitis delta group.

  18. Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia.

    PubMed

    Tsatsralt-Od, Bira; Takahashi, Masaharu; Endo, Kazunori; Buyankhuu, Osorjin; Baatarkhuu, Oidov; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2006-05-01

    One hundred ten consecutive patients (60 males and 50 females; age, mean +/- standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B + D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia.

  19. Packaging of hepatitis delta virus RNA via the RNA-binding domain of hepatitis delta antigens: different roles for the small and large delta antigens.

    PubMed Central

    Wang, H W; Chen, P J; Lee, C Z; Wu, H L; Chen, D S

    1994-01-01

    Hepatitis delta virus (HDV) is composed of four specific components. The first component is envelope protein which contains hepatitis B surface antigens. The second and third components are nucleocapsid proteins, referred to as small and large hepatitis delta antigens (HDAgs). The final component is a single-stranded circular RNA molecule known as the viral genome. In order to study the mechanism of HDV RNA packaging, a four-plasmid cotransfection system in which each viral component was provided by a separate plasmid was employed. Virus-like particles released from Huh-7 cells receiving such a cotransfection were found to contain HDV RNA along with three proteins. Therefore, the four-plasmid cotransfection system could lead to successful HDV RNA packaging in vitro. The system was then used to show that the large HDAg alone was able to achieve a low level of HDV RNA packaging. Analysis of a variety of large HDAg mutants revealed that the RNA-binding domain was essential for viral RNA packaging. By increasing the incorporation of small HDAg into virus-like particles, we found a three- to fourfold enhancement of HDV RNA packaging. This effect was probably through a direct binding of HDV RNA, independent from that of large HDAg, with the small HDAg. The subsequent RNA-protein complex was packaged into particles. The results provided insight into the roles and functional domains of small and large HDAgs in HDV RNA packaging. Images PMID:8083975

  20. A conformational switch controls hepatitis delta virus ribozyme catalysis.

    PubMed

    Ke, Ailong; Zhou, Kaihong; Ding, Fang; Cate, Jamie H D; Doudna, Jennifer A

    2004-05-13

    Ribozymes enhance chemical reaction rates using many of the same catalytic strategies as protein enzymes. In the hepatitis delta virus (HDV) ribozyme, site-specific self-cleavage of the viral RNA phosphodiester backbone requires both divalent cations and a cytidine nucleotide. General acid-base catalysis, substrate destabilization and global and local conformational changes have all been proposed to contribute to the ribozyme catalytic mechanism. Here we report ten crystal structures of the HDV ribozyme in its pre-cleaved state, showing that cytidine is positioned to activate the 2'-OH nucleophile in the precursor structure. This observation supports its proposed role as a general base in the reaction mechanism. Comparison of crystal structures of the ribozyme in the pre- and post-cleavage states reveals a significant conformational change in the RNA after cleavage and that a catalytically critical divalent metal ion from the active site is ejected. The HDV ribozyme has remarkable chemical similarity to protein ribonucleases and to zymogens for which conformational dynamics are integral to biological activity. This finding implies that RNA structural rearrangements control the reactivity of ribozymes and ribonucleoprotein enzymes.

  1. Prevalence of Hepatitis Delta Virus (HDV) Infection in Chronic Hepatitis B Patients with Unusual Clinical Pictures

    PubMed Central

    Ghamari, Shiva; Alavian, Seyed Moayed; Rizzetto, Mario; Olivero, Antonella; Smedile, Antonina; Khedive, Abulfazl; Alavian, Seyed Ehsan; Zolfaghari, Mohammad Reza; Jazayeri, Seyed Mohammad

    2013-01-01

    Background Probably 5% of the HBV carriers have HDV super infection. The risk of fulminant hepatitis, cirrhosis and hepatocellular carcinoma is higher in superinfection than the settings when HBV is alone. Objectives The aim of this study was to evaluate the prevalence of HDV in Iranian HBV isolates and to compare their clinical and virological pictures as well as their HDV genetic variations with other worldwide isolates. Patients and Methods 81 carriers with positive results for HBsAg with upper limit ranges of ALT and low or undetectable levels of HBV viral load who did not respond to HBV therapy were selected. After RT amplification of HDV Delta antigen, direct sequencing and phylogenetic study were performed to explore the genotype(s) and nucleotide/amino acid variations. Results 12 (14.8%) patients had positive results for both HDV RNA and anti-HDV. The mean ALT level was higher in HDV positive patients (75.9 U/ML) than HBV-mono-infected individuals; however, the mean HBV viral load was lower in coinfected patients than HBV-mono-infected patients. Phylogenetically, genotype I was the only detected genotype, and the most closely related isolates were of Turkish, Italian and Mongolian origin. Within the delta Ag, there were 326 nucleotide mutations, of which 111 and 215 were silent and missense, respectively. The total number of amino acid substitution was 148; most were located in known functional/epitopic domains. There was no correlation between the numbers of amino acid mutations, with clinical, virological status of the patients. Conclusions HDV should be suspected in HBV carriers with unusual clinical and virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish sequences proposed a common Caucasian origin for the distribution of HDV genotype I in this ethnic group. PMID:24098308

  2. Treatment of Delta Hepatitis: Today and in the Future - A review.

    PubMed

    Bahcecioglu, Ibrahim Halil; Sahin, Abdurrahman

    2017-04-01

    Hepatitis delta virus (HDV) is a defective satellite virus and propagates in the presence of Hepatitis B virus (HBV) surface antigen (HBsAg). Approximately 5% of the people who infected with HBV are also infected with HDV. Chronic hepatitis caused by delta is the most severe form of chronic viral hepatitis including accelerated fibrosis, liver decompensation and development of hepatocellular carcinoma. Interferon-based therapies still remain the only treatment option of the hepatitis delta. The beneficiary effects of the interferon-based therapies, however, stop frequently with termination of the given therapy and relapse rate is very high. Accordingly, the efficiency rate of this treatment does not exceed 30%. On the other hand, serious side effects of interferons are another troublesome leading to withdrawal of the therapy. The main goal of the current treatments is clearance of HBsAg. There is no available drug acting directly against the HDV. New therapies interacting with HDV life cycle are under investigation. While prenylation inhibitors act on merely HDV, viral entry inhibitors and HBsAg release inhibitors would be used in the treatment of both HBV and HDV. We hope that in the future, the use of novel therapies and HBV vaccination provide to clinicians to cope with this troublesome agent.

  3. Expression of the hepatitis delta virus large and small antigens in transgenic mice.

    PubMed Central

    Guilhot, S; Huang, S N; Xia, Y P; La Monica, N; Lai, M M; Chisari, F V

    1994-01-01

    Simultaneous infection with hepatitis delta virus (HDV) and hepatitis B virus (HBV) in humans is often associated with severe viral liver disease including fulminant hepatitis. Since HBV is thought to be noncytopathic to the hepatocyte, the enhanced disease severity observed during dual infection has been attributed to either simultaneous immune responses against the two viruses or direct cytotoxic effects of HDV products on the hepatocyte or both. To examine these alternate possibilities, we produced transgenic mice that express the small and large delta antigens (HDAg) in hepatocyte nuclei at levels equal to those observed during natural HDV infection. No biological or histopathological evidence of liver disease was detectable during 18 months of observation, suggesting that neither the large nor small form of HDAg is directly cytopathic to the hepatocyte in vivo. Images PMID:8289334

  4. Cloned hepatitis delta virus cDNA is infectious in the chimpanzee.

    PubMed Central

    Sureau, C; Taylor, J; Chao, M; Eichberg, J W; Lanford, R E

    1989-01-01

    A head-to-tail trimer of a full-length cDNA clone of the hepatitis delta virus (HDV) genome was examined for infectivity by direct inoculation into the liver of a chimpanzee that was already infected with hepatitis B virus. Five weeks after inoculation, a marked elevation of serum alanine aminotransferase activity was observed, followed by the appearance of high levels of HDV RNA and antigen in both liver and serum and a high level of viral particles in the serum. A transient suppression of hepatitis B virus replication was evident during the acute phase of HDV infection. Seroconversion for antibodies to delta antigen occurred 3 weeks after the onset of the disease. These results demonstrate that a typical HDV infection can be initiated by inoculation of a susceptible animal with recombinant HDV cDNA. Images PMID:2778877

  5. Diagnostic and prognostic significance of the IgM antibody to the Hepatitis delta virus

    SciTech Connect

    Farci, P.; Gerin, J.L.; Aragona, M.; Lindsey, I.; Crivelli, O.; Balestrieri, A.; Smedile, A.; Thomas, H.C.; Rizzetto, M.

    1986-03-21

    The IgM class antibody to the hepatitis delta virus (HDV) was determined in different clinical categories of hepatitis B surface antigen carriers infected by the HDV (positive in the test for total antibody to HDV). The IgM antibody was found at high titers in each 70 patients with inflammatory liver disease and at a low titer in one six patients with inactive cirrhosis; it was not found in eight carriers with normal liver histology. Testing for Igm antibody to HDV distinguishes hepatitis B surface antigen carriers who have underlying inflammatory HDV liver disease from those with past HDV infection and provides prognostic information on the course of chronic HDV hepatitis.

  6. [The molecular biology of hepatitis C virus].

    PubMed

    Koutsoudakis, George; Forns, Xavier; Pérez-Del-Pulgar, Sofía

    2013-04-01

    Since the discovery of the hepatitis C virus (HCV), a plethora of experimental models have evolved, allowing the virus's life cycle and the pathogenesis of associated liver diseases to be investigated. These models range from inoculation of cultured cells with serum from patients with hepatitis C to the use of surrogate models for the study of specific stages of the HCV life cycle: retroviral pseudoparticles for the study of HCV entry, replicons for the study of HCV replication, and the HCV cell culture model, which reproduces the entire life cycle (replication and production of infectious particles). The use of these tools has been and remains crucial to identify potential therapeutic targets in the different stages of the virus's life cycle and to screen new antiviral drugs. A clear example is the recent approval of two viral protease inhibitors (boceprevir and telaprevir) in combination with pegylated interferon and ribavirin for the treatment of chronic hepatitis C. This review analyzes the advances made in the molecular biology of HCV and highlights possible candidates as therapeutic targets for the treatment of HCV infection.

  7. Advanced Molecular Surveillance of Hepatitis C Virus

    PubMed Central

    Gonçalves Rossi, Livia Maria; Escobar-Gutierrez, Alejandro; Rahal, Paula

    2015-01-01

    Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted. PMID:25781918

  8. Advanced molecular surveillance of hepatitis C virus.

    PubMed

    Rossi, Livia Maria Gonçalves; Escobar-Gutierrez, Alejandro; Rahal, Paula

    2015-03-13

    Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted.

  9. Characterization of the nuclear localization signal of the hepatitis delta virus antigen

    SciTech Connect

    Alves, Carolina; Freitas, Natalia; Cunha, Celso

    2008-01-05

    The delta antigen (HDAg) is the only protein encoded by the hepatitis delta virus (HDV) RNA genome. The HDAg contains an RNA binding domain, a dimerization domain, and a nuclear localization signal (NLS). The nuclear import of HDV RNPs is thought to be one of the first tasks of the HDAg during the HDV replication cycle. Using c-myc-PK fusions with several regions of the HDAg in transfection assays in Huh7 cells, we found that the HDAg NLS consists of a single stretch of 10 amino acids, EGAPPAKRAR, located in positions 66-75. Deletion and mutation analysis of this region showed that both the acidic glutamic acid residue at position 66 and the basic arginine residue at position 75 are essential for promoting nuclear import.

  10. Molecular Pathophysiology of Hepatic Glucose Production

    PubMed Central

    Sharabi, Kfir; Tavares, Clint D. J.; Rines, Amy K.; Puigserver, Pere

    2015-01-01

    Maintaining blood glucose concentration within a relatively narrow range through periods of fasting or excess nutrient availability is essential to the survival of the organism. This is achieved through an intricate balance between glucose uptake and endogenous glucose production to maintain constant glucose concentrations. The liver plays a major role in maintaining normal whole body glucose levels by regulating the processes of de novo glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis), thus controlling the levels of hepatic glucose release. Aberrant regulation of hepatic glucose production (HGP) can result in deleterious clinical outcomes, and excessive HGP is a major contributor to the hyperglycemia observed in Type 2 diabetes mellitus (T2DM). Indeed, adjusting glycaemia as close as possible to a non-diabetic range is the foremost objective in the medical treatment of patients with T2DM and is currently achieved in the clinic primarily through suppression of HGP. Here, we review the molecular mechanisms controlling HGP in response to nutritional and hormonal signals and discuss how these signals are altered in T2DM. PMID:26549348

  11. Molecular pathophysiology of hepatic glucose production.

    PubMed

    Sharabi, Kfir; Tavares, Clint D J; Rines, Amy K; Puigserver, Pere

    2015-12-01

    Maintaining blood glucose concentration within a relatively narrow range through periods of fasting or excess nutrient availability is essential to the survival of the organism. This is achieved through an intricate balance between glucose uptake and endogenous glucose production to maintain constant glucose concentrations. The liver plays a major role in maintaining normal whole body glucose levels by regulating the processes of de novo glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis), thus controlling the levels of hepatic glucose release. Aberrant regulation of hepatic glucose production (HGP) can result in deleterious clinical outcomes, and excessive HGP is a major contributor to the hyperglycemia observed in Type 2 diabetes mellitus (T2DM). Indeed, adjusting glycemia as close as possible to a non-diabetic range is the foremost objective in the medical treatment of patients with T2DM and is currently achieved in the clinic primarily through suppression of HGP. Here, we review the molecular mechanisms controlling HGP in response to nutritional and hormonal signals and discuss how these signals are altered in T2DM.

  12. Protein-induced alterations in murine hepatic alpha-aminoadipate delta-semialdehyde synthase activity are mediated posttranslationally.

    PubMed

    Kiess, Aaron S; Cleveland, Beth M; Wilson, Matthew E; Klandorf, Hillar; Blemings, Kenneth P

    2008-12-01

    The molecular mechanisms responsible for alterations in lysine alpha-ketoglutarate reductase (LKR) activity are unknown. Therefore, the aim of these studies was to discern the mechanism(s) responsible for induction of hepatic LKR activity in rodents fed excess dietary protein. Four studies were conducted that used 84 mice. Mice were fed either a high-protein (50% casein) or adequate-protein (20% casein) diet in powder form in study 1 and a high-protein (46% casein) or adequate-protein (21% casein) diet in pellet form in the remaining studies. No significant differences in weight gain between the mice fed the different diets were detected. As expected, mice fed high-protein diets had a greater (P< .05) LKR activity in all 4 experiments. Mice fed high- and adequate-protein diets for 8 days showed no difference (P> .1) in alpha-aminoadipate delta-semialdehyde synthase (AASS) mRNA in experiment 1. However, after pooling the data from the remaining 3 experiments, mice receiving the high-protein diet had greater (P< .05) AASS mRNA compared to mice fed the adequate protein diet. In this investigation, no differences (P> .1) in AASS protein abundance were detected. The results are consistent with a mechanism in which posttranslational regulation is responsible for hepatic induction of LKR activity in mice fed high-protein diets.

  13. Analysis of a hepatitis delta virus isolate from the Central African Republic.

    PubMed

    Langon, T; Fillon, S; Pichoud, C; Hantz, O; Trépo, C; Kay, A

    1998-01-01

    Based on the analysis of HDV genomes from different areas of the world, three genotypes of HDV have been identified. Genotype I is the most prevalent and widespread. Genotype II is represented by two isolates from Japan and Taiwan. Genotype III has been found only in the Amazonian basin where it is associated with a history of severe disease, fulminant hepatitis with microvesicular steatosis (spongiocytosis). We report here the cloning and the analysis of the complete viral genome from woodchuck serum-derived HDV RNA after transmission from Central African Republic (RCA) patients with fulminant spongiocytic delta hepatitis. Two overlapping cDNA fragments, covering the entire HDV genome, were generated by RT-PCR and cloned. Three clones obtained from each fragment were fully sequenced. A complete consensus RCA HDV genome was reconstituted. The individual and the consensus nucleotide sequences were compared with those of 16 other fully sequenced isolates belonging to the three genotypes. Phylogenetic trees generated by the neighbour joining method firmly place our isolate in genotype I, and show that this RCA isolate differs significantly from the east African isolates previously analysed. Transfection experiments showed that the isolate is replication-competent, but less so than the control "wild-type" strain. Two novel mutations encountered in this work, one in the antigenomic ribozyme sequence and one affecting delta antigen, were studied.

  14. Computational design of d-peptide inhibitors of hepatitis delta antigen dimerization

    NASA Astrophysics Data System (ADS)

    Elkin, Carl D.; Zuccola, Harmon J.; Hogle, James M.; Joseph-McCarthy, Diane

    2000-11-01

    Hepatitis delta virus (HDV) encodes a single polypeptide called hepatitis delta antigen (DAg). Dimerization of DAg is required for viral replication. The structure of the dimerization region, residues 12 to 60, consists of an anti-parallel coiled coil [Zuccola et al., Structure, 6 (1998) 821]. Multiple Copy Simultaneous Searches (MCSS) of the hydrophobic core region formed by the bend in the helix of one monomer of this structure were carried out for many diverse functional groups. Six critical interaction sites were identified. The Protein Data Bank was searched for backbone templates to use in the subsequent design process by matching to these sites. A 14 residue helix expected to bind to the d-isomer of the target structure was selected as the template. Over 200 000 mutant sequences of this peptide were generated based on the MCSS results. A secondary structure prediction algorithm was used to screen all sequences, and in general only those that were predicted to be highly helical were retained. Approximately 100 of these 14-mers were model built as d-peptides and docked with the l-isomer of the target monomer. Based on calculated interaction energies, predicted helicity, and intrahelical salt bridge patterns, a small number of peptides were selected as the most promising candidates. The ligand design approach presented here is the computational analogue of mirror image phage display. The results have been used to characterize the interactions responsible for formation of this model anti-parallel coiled coil and to suggest potential ligands to disrupt it.

  15. Evidence of an Exponential Decay Pattern of the Hepatitis Delta Virus Evolution Rate and Fluctuations in Quasispecies Complexity in Long-Term Studies of Chronic Delta Infection

    PubMed Central

    Homs, Maria; Rodriguez-Frias, Francisco; Gregori, Josep; Ruiz, Alicia; Reimundo, Pilar; Casillas, Rosario; Tabernero, David; Godoy, Cristina; Barakat, Salma; Quer, Josep; Riveiro-Barciela, Mar; Roggendorf, Michael; Esteban, Rafael; Buti, Maria

    2016-01-01

    Chronic HDV infection can cause a severe form of viral hepatitis for which there is no specific treatment. Characterization of the hepatitis B or C viral quasispecies has provided insight into treatment failure and disease recurrence following liver transplantation, has proven useful to understand hepatitis B e antigen seroconversion, and has helped to predict whether hepatitis C infection will resolve or become chronic. It is likely that characterization of the hepatitis delta virus (HDV) quasispecies will ultimately have similar value for the management of this infection. This study sought to determine the RNA evolution rates in serum of chronic hepatitis delta (CHD) treatment-naïve patients, using next-generation sequencing methods. The region selected for study encompassed nucleotide positions 910 to 1270 of the genome and included the amber/W codon. Amber/W is a substrate of the editing process by the ADAR1 host enzyme and is essential for encoding the 2 delta antigens (HDAg). The amber codon encodes the small (unedited) HDAg form and the W codon the large (edited) HDAg form. The evolution rate was analyzed taking into account the time elapsed between samples, the percentage of unedited and edited genomes, and the complexity of the viral population. The longitudinal studies included 29 sequential samples from CHD patients followed up for a mean of 11.5 years. In total, 121,116 sequences were analyzed. The HDV evolution rate ranged from 9.5x10-3 to 1.2x10-3 substitutions/site/year and showed a negative correlation with the time elapsed between samples (p<0.05). An accumulation of transition-type changes was found to be responsible for higher evolution rates. The percentages of unedited and edited genomes and the quasispecies complexity showed no relationships with the evolution rate, but the fluctuations in the percentages of genomes and in complexity suggest continuous adaptation of HDV to the host conditions. PMID:27362848

  16. Evidence of an Exponential Decay Pattern of the Hepatitis Delta Virus Evolution Rate and Fluctuations in Quasispecies Complexity in Long-Term Studies of Chronic Delta Infection.

    PubMed

    Homs, Maria; Rodriguez-Frias, Francisco; Gregori, Josep; Ruiz, Alicia; Reimundo, Pilar; Casillas, Rosario; Tabernero, David; Godoy, Cristina; Barakat, Salma; Quer, Josep; Riveiro-Barciela, Mar; Roggendorf, Michael; Esteban, Rafael; Buti, Maria

    2016-01-01

    Chronic HDV infection can cause a severe form of viral hepatitis for which there is no specific treatment. Characterization of the hepatitis B or C viral quasispecies has provided insight into treatment failure and disease recurrence following liver transplantation, has proven useful to understand hepatitis B e antigen seroconversion, and has helped to predict whether hepatitis C infection will resolve or become chronic. It is likely that characterization of the hepatitis delta virus (HDV) quasispecies will ultimately have similar value for the management of this infection. This study sought to determine the RNA evolution rates in serum of chronic hepatitis delta (CHD) treatment-naïve patients, using next-generation sequencing methods. The region selected for study encompassed nucleotide positions 910 to 1270 of the genome and included the amber/W codon. Amber/W is a substrate of the editing process by the ADAR1 host enzyme and is essential for encoding the 2 delta antigens (HDAg). The amber codon encodes the small (unedited) HDAg form and the W codon the large (edited) HDAg form. The evolution rate was analyzed taking into account the time elapsed between samples, the percentage of unedited and edited genomes, and the complexity of the viral population. The longitudinal studies included 29 sequential samples from CHD patients followed up for a mean of 11.5 years. In total, 121,116 sequences were analyzed. The HDV evolution rate ranged from 9.5x10-3 to 1.2x10-3 substitutions/site/year and showed a negative correlation with the time elapsed between samples (p<0.05). An accumulation of transition-type changes was found to be responsible for higher evolution rates. The percentages of unedited and edited genomes and the quasispecies complexity showed no relationships with the evolution rate, but the fluctuations in the percentages of genomes and in complexity suggest continuous adaptation of HDV to the host conditions.

  17. Hepatitis Delta Virus Minimal Substrates Competent for Editing by ADAR1 and ADAR2

    PubMed Central

    Sato, Shuji; Wong, Swee Kee; Lazinski, David W.

    2001-01-01

    A host-mediated RNA-editing event allows hepatitis delta virus (HDV) to express two essential proteins, the small delta antigen (HDAg-S) and the large delta antigen (HDAg-L), from a single open reading frame. One or several members of the ADAR (adenosine deaminases that act on RNA) family are thought to convert the adenosine to an inosine (I) within the HDAg-S amber codon in antigenomic RNA. As a consequence of replication, the UIG codon is converted to a UGG (tryptophan [W]) codon in the resulting HDAg-L message. Here, we used a novel reporter system to monitor the editing of the HDV amber/W site in the absence of replication. In cultured cells, we observed that both human ADAR1 (hADAR1) and hADAR2 were capable of editing the amber/W site with comparable efficiencies. We also defined the minimal HDV substrate required for hADAR1- and hADAR2-mediated editing. Only 24 nucleotides from the amber/W site were sufficient to enable efficient editing by hADAR1. Hence, the HDV amber/W site represents the smallest ADAR substrate yet identified. In contrast, the minimal substrate competent for hADAR2-mediated editing contained 66 nucleotides. PMID:11507200

  18. The prevalence and impact of brucellosis in patients with hepatitis delta virus infection: inside the Brucella outbreak with cirrhosis

    PubMed Central

    Dulger, Ahmet Cumhur; Suvak, Ozlem; Yesilyurt, Aysun Özel; Gultepe, Bilge; Guducuoglu, Huseyin

    2017-01-01

    Introduction Hepatitis D virus (HDV) infection is a serious health problem leading to cirrhosis and hepatocellular carcinoma (HCC). Despite evidence that zoonotic infections are associated with end-stage liver disease, brucellosis in patients with delta hepatitis related to liver disease has not been well characterized. So, we examined this relationship using recent hospital-based data. Material and methods We analyzed data from 96 delta hepatitis patients (mean age: 52.5 ±12.8 years; 50 male; 52 cirrhotics) and 117 (mean age: 50.4 ±7 years; 60 male) control subjects who were selected from patients with splenomegaly. The Brucella Wright test in connection with blood culture was used to detect active Brucella infection. Demographic features, laboratory data, results of ultrasonographic examination of the abdomen and Wright agglutination titers were compared between groups. Results There were 9 (9%) patients with active brucellosis in delta hepatitis patients. Compared to the control group, there was a statistically significant difference between groups in terms of having active brucellosis (9 vs. 2 patients; p < 0.001). Higher MELD scores were also associated with active Brucella infection (p < 0.005). Conclusions Patients with chronic hepatitis D related cirrhosis (CHD-C) were at risk of developing brucellosis requiring hospitalization. Higher Wright titers among patients with more advanced liver disease may reflect a unique phenomenon that requires further investigation to determine underlying causative factors. PMID:28261291

  19. Adoptive transfer of unresponsiveness to allogeneic skin grafts with hepatic gamma delta + T cells.

    PubMed Central

    Gorczynski, R M

    1994-01-01

    C3H/HEJ mice injected with irradiated multiple minor incompatible B10.BR lymphoid cells via the portal vein showed delayed rejection of subsequent B10.BR skin grafts. Similar delayed rejection was produced by lateral tail vein injection of B10.BR hepatic mononuclear cells or H-2k cells pulsed in vivo with B10 minor histocompatibility antigens. Inhibition of C3H anti-B10.BR immunity in vivo (assessed by delayed graft rejection) and in vitro (assessed by B10.BR-induced lymphokine production) can be transferred by radioresistant, plastic-adherent F4/80+33D1-CD4-CD8-alpha beta TcR-gamma delta TcR- mononuclear hepatic cells from (C3H/HEJ x C3H.SW)F1 mice injected 36 hr earlier with 100 x 10(6) irradiated spleen cells. By 10 days post-injection, cells transferring delayed rejection are radiosensitive, plastic non-adherent, F4/80-33D1-CD4-CD8- alpha beta Tc+- gamma delta TcR+ cells. Injection of interleukin-2 (IL-2) in vivo into mice receiving pretreatment with B10.BR cells via the portal vein, or adoptive transfer into such mice of immune anti-B10.BR lymphoid cells, abolished delayed rejection on subsequent skin grafting. Delayed rejection or modulation of lymphokine production was associated in all cases with suppression of IL-2 production and preferential retention of IL-4 production from cells stimulated in vitro. PMID:8132216

  20. Prominent polypurine and polypyrimidine tracts in plant viroids and in RNA of the human hepatitis delta agent.

    PubMed Central

    Branch, A D; Lee, S E; Neel, O D; Robertson, H D

    1993-01-01

    To seek patterns of nucleotide usage in the three types of circular subviral RNA pathogens, trimer frequencies and nearest-neighbor biases were studied in 12 plant viroid sequences; five sequences of circular plant viral satellite RNAs; and the sequence of RNA from the human hepatitis delta agent. The viroids and RNA of the delta agent contain tracts of polypurines and polypyrimidines which make up substantial portions of their genomes. Such tracts are not common in the virusoids or in the satellite RNA of tobacco ringspot virus. Viroids, the delta hepatitis agent, and the circular satellite RNAs of certain plant viruses have several features in common: all have circular genomic RNA and replicate through an RNA to RNA rolling circle replication cycle. However, virusoids and related satellite RNAs are directly or indirectly dependent on their helper viruses for replication, while the delta agent and viroids are not. The difference in the pattern of nucleotide usage between the plant viral satellite RNAs on the one hand, and viroids and delta RNA on the other, may relate to this difference in replication strategy. PMID:7688455

  1. Molecular Pathology of Hepatic Neoplasms: Classification and Clinical Significance

    PubMed Central

    Walther, Zenta; Jain, Dhanpat

    2011-01-01

    Recent technological advances have enabled investigators to characterize the molecular genetics and genomics of hepatic neoplasia in remarkable detail. From these studies, an increasing number of molecular markers are being identified that correlate with clinically important tumor phenotypes. This paper discusses current knowledge relevant to the molecular classification of epithelial primary hepatic tumors that arise in adults, including focal nodular hyperplasia (FNH), hepatocellular adenoma (HCA), hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC. Genetic analysis has defined molecular subtypes of HCA that are clinicopathologically distinct and can be distinguished through immunohistochemistry. Gene expression studies have identified molecular signatures of progression from dysplastic nodules (DNs) to early HCC in cirrhosis. Analyses of the mutational spectra, chromosomal aberrations and instability, transcriptomics, and microRNA profiles of HCC have revealed the existence of biologically distinct subtypes of this common malignancy, with prognostic implications. Molecular characterization of biliary and hepatic progenitor cell phenotypes in liver cancer has shed new light on the histogenesis of these tumors and has focused attention on novel therapeutic targets. In coming years, the molecular classification of hepatic neoplasms will be increasingly valuable for guiding patient care, as targeted therapies for liver cancer are developed and brought into clinical practice. PMID:21559202

  2. [Hepatitis E: molecular virology, epidemiology and pathogenesis].

    PubMed

    Rodríguez-Frias, Francisco; Jardi, Rosendo; Buti, María

    2012-12-01

    Hepatitis E represents a significant proportion of enteric transmitted liver diseases and poses a major public health problem, mainly associated with epidemics due to contamination of water supplies, especially in developing countries. Hepatitis E virus (HEV) is responsible for self-limiting acute liver oral-faecal infections. In industrialised countries, acute hepatitis E is sporadic, detected in travellers from endemic areas but also in sporadic cases with no risk factors. HEV is a non-enveloped virus with a single-stranded RNA genome classified into 4 genotypes and a single serotype. Genotypes 1 and 2 only infect humans, and are predominant in the developing countries, while 3 and 4 are predominant in industrialised countries, and also infect other species of mammals, especially pigs, and multiple evidence classifies HEV as a zoonotic agent. Some HEV chronic infections have recently been reported in kidney and liver transplant patients. The mortality rate of HEV infection is greater than hepatitis A. In addition to faecal-oral transmission, parenteral transmission of HEV has also been reported. Several vaccines are currently in development. The severity of this infection in some groups of patients, especially pregnant women, and the occurrence of chronic hepatitis, even with progression to cirrhosis, have raised interest in the application of interferon and/or ribavirin therapy.

  3. An outbreak of fulminant hepatitis delta in the Waorani, an indigenous people of the Amazon basin of Ecuador.

    PubMed

    Manock, S R; Kelley, P M; Hyams, K C; Douce, R; Smalligan, R D; Watts, D M; Sharp, T W; Casey, J L; Gerin, J L; Engle, R; Alava-Alprecht, A; Martínez, C M; Bravo, N B; Guevara, A G; Russell, K L; Mendoza, W; Vimos, C

    2000-01-01

    An outbreak of delta hepatitis occurred during 1998 among the Waorani of the Amazon basin of Ecuador. Among 58 people identified with jaundice, 79% lived in four of 22 Waorani communities. Serum hepatitis B surface antigen (HBsAg) was found in the sera of 54% of the jaundiced persons, and 14% of asymptomatic persons. Ninety-five percent of 105 asymptomatic Waorani had hepatitis B core (HBc) IgG antibody, versus 98% of 51 with jaundice. These data confirm that hepatitis B virus (HBV) infection is highly endemic among the Waorani. Sixteen of 23 (70%) HBsAg carriers identified at the onset of the epidemic had serologic markers for hepatitis D virus (HDV) infection. All 16 were jaundiced, where as only two of seven (29%) with negative HDV serology were jaundiced (P = .0006). The delta cases clustered in families, 69% were children and most involved superinfection of people chronically infected with HBV. The data suggest that HDV spread rapidly by a horizontal mode of transmission other than by the sexual route.

  4. DELTAE

    SciTech Connect

    Ward, W.C. ); Swift, G.W. )

    1993-11-01

    In thermoacoustic engines and refrigerators, and in many simple acoustic systems, a one dimensional wave equation determines the spatial dependence of the acoustic pressure and velocity. DELTAE numerically integrates such wave equations in the acoustic approximation, in gases or liquids, in user-defined geometries. Boundary conditions can include conventional acoustic boundary conditions of geometry and impedance, as well as temperature and thermal power in thermoacoustic systems. DELTAE can be used easily for apparatus ranging from simple duct networks and resonators to thermoacoustic engines refrigerators and combinations thereof. It can predict how a given apparatus will perform, or can allow the user to design an apparatus to achieve desired performance. DELTAE views systems as a series of segments; twenty segment types are supported. The purely acoustic segments include ducts and cones, and lumped impedances including compliances, series impedances, and endcaps. Electroacoustics tranducer segments can be defined using either frequency-independent coefficients or the conventional parameters of loudspeaker-style drivers: mass, spring constant, magnetic field strength, etc. Tranducers can be current driven, voltage driven, or connected to an electrical load impedance. Thermoacoustic segment geometries include parallel plates, circular and rectangular pores, and pin arrays. Side branches can be defined with fixed impedances, frequency-dependent radiation impedances, or as an auxiliary series of segments of any types. The user can select working fluids from among air, helium, neon, argon, hydrogen, deuterium, carbon dioxide, nitrogen, helium-argon mixtures, helium-xenon mixtures, liquid sodium, and eutectic sodium-potassium. Additional fluids and solids can be defined by the user.

  5. Delta opioid receptor analgesia: recent contributions from pharmacology and molecular approaches

    PubMed Central

    Gavériaux-Ruff, Claire; Kieffer, Brigitte Lina

    2012-01-01

    Delta opioid receptors represent a promising target for the development of novel analgesics. A number of tools have been developed recently that have significantly improved our knowledge of delta receptor function in pain control. These include several novel delta agonists with potent analgesic properties, as well as genetic mouse models with targeted mutations in the delta opioid receptor gene. Also, recent findings have further documented the regulation of delta receptor function at cellular level, which impacts on the pain-reducing activity of the receptor. These regulatory mechanisms occur at transcriptional and post-translational levels, along agonist-induced receptor activation, signaling and trafficking, or in interaction with other receptors and neuromodulatory systems. All these tools for in vivo research, as well as proposed mechanisms at molecular level, have tremendously increased our understanding of delta receptor physiology, and contribute to designing innovative strategies for the treatment of chronic pain and other diseases such as mood disorders. PMID:21836459

  6. Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B

    PubMed Central

    Fattovich, G; Giustina, G; Christensen, E; Pantalena, M; Zagni, I; Realdi, G; Schalm, S

    2000-01-01

    BACKGROUND—The effect of hepatitis delta virus (HDV) infection on the clinical course of cirrhosis type B is poorly defined.
AIMS—To investigate the impact of HDV status on morbidity and mortality in cirrhosis type B.
PATIENTS/METHODS—Retrospective cohort study of 200 Western European patients with compensated cirrhosis type B followed for a median period of 6.6 years.
RESULTS—At diagnosis, 20% of patients had antibodies to HDV (anti-HDV); median age was lower in anti-HDV positive cirrhotics (34 v 48 years respectively). Kaplan-Meier five year probability of hepatocellular carcinoma (HCC) was 6, 10, and 9% in anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 22, 16, and 19% and for survival they were 92, 89, and 83% respectively. Cox regression analysis identified age, albumin concentration, γ-globulin concentration, and HDV status as significant independent prognostic variables. After adjustment for clinical and serological differences at baseline, the risk (95% confidence interval) for HCC, decompensation, and mortality was increased by a factor of 3.2 (1.0 to 10), 2.2 (0.8 to 5.7), and 2.0 (0.7 to 5.7) respectively in anti-HDV positive relative to HDV negative cirrhotic patients. The adjusted estimated five year risk for HCC was 13, 4, and 2% for anti-HDV positive/HBeAg negative, anti-HDV negative/HBeAg negative, and anti-HDV negative/HBeAg positive cirrhotics respectively; the corresponding figures for decompensation were 18, 8, and 14% and for survival 90, 95, and 93% respectively.
CONCLUSIONS—HDV infection increases the risk for HCC threefold and for mortality twofold in patients with cirrhosis type B.


Keywords: delta hepatitis; prognosis; hepatocellular carcinoma; decompensation; survival PMID:10673308

  7. Prokaryotic Expression, Purification and Immunogenicity in Rabbits of the Small Antigen of Hepatitis Delta Virus.

    PubMed

    Tunitskaya, Vera L; Eliseeva, Olesja V; Valuev-Elliston, Vladimir T; Tyurina, Daria A; Zakirova, Natalia F; Khomich, Olga A; Kalis, Martins; Latyshev, Oleg E; Starodubova, Elizaveta S; Ivanova, Olga N; Kochetkov, Sergey N; Isaguliants, Maria G; Ivanov, Alexander V

    2016-10-20

    Hepatitis delta virus (HDV) is a viroid-like blood-borne human pathogen that accompanies hepatitis B virus infection in 5% patients. HDV has been studied for four decades; however, the knowledge on its life-cycle and pathogenesis is still sparse. The studies are hampered by the absence of the commercially-available HDV-specific antibodies. Here, we describe a set of reproducible methods for the expression in E. coli of His-tagged small antigen of HDV (S-HDAg), its purification, and production of polyclonal anti-S-HDAg antibodies in rabbits. S-HDAg was cloned into a commercial vector guiding expression of the recombinant proteins with the C-terminal His-tag. We optimized S-HDAg protein purification procedure circumventing a low affinity of the His-tagged S-HDAg to the Ni-nitrilotriacetyl agarose (Ni-NTA-agarose) resin. Optimization allowed us to obtain S-HDAg with >90% purity. S-HDAg was used to immunize Shinchilla grey rabbits which received 80 μg of S-HDAg in two subcutaneous primes in the complete, followed by four 40 μg boosts in incomplete Freunds adjuvant. Rabbits were bled two weeks post each boost. Antibody titers determined by indirect ELISA exceeded 10⁷. Anti-S-HDAg antibodies detected the antigen on Western blots in the amounts of up-to 100 pg. They were also successfully used to characterize the expression of S-HDAg in the eukaryotic cells by immunofluorescent staining/confocal microscopy.

  8. Epidemiological update of hepatitis B, C and delta in Latin America.

    PubMed

    Alvarado-Mora, Mónica V; Pinho, João R Rebello

    2013-01-01

    Viral hepatitis B, C and delta still remain a serious problem in Latin America. Data from the 1980s indicated that HBV and HDV infection are the main causes of chronic hepatitis. However, the spread of HBV infection could be controlled through the implementation of immunization programmes. Different countries from Mexico to Argentina display marked differences in terms of HBV genotype distribution. HBV genotype F has been identified as the most frequent in most Latin America countries, except for Mexico and Brazil, where genotypes H and A are the most frequent, respectively. In Latin America, the overall prevalence of HCV antibody is estimated to be 1.5%. Latin American countries have been very proactive in screening their blood supplies, thus minimizing risk of HCV transmission through transfusion. The number of diagnosed and treated patients is still low, thereby increasing the burden of complications such as liver cirrhosis or hepatocellular carcinoma. The most prevalent HCV genotype is 1, which is the genotype with the greatest worldwide spread, but it is a different genotype from other regions like Africa and Asia. HDV is present worldwide but its distribution pattern is not uniform. HDV was recently detected in novel geographic regions, reinforcing that it is a very serious health threat in under-developed countries. The main prevalence areas are the Mediterranean basin, the Middle East, central and northern Asia, western and central Africa, the Amazonian basin (Brazil, Peru, Venezuela and Colombia) and the Pacific islands. Novel strategies to increase HBV immunization in the Latin American population are needed to warrant thorough coverage in the rural areas.

  9. Prokaryotic Expression, Purification and Immunogenicity in Rabbits of the Small Antigen of Hepatitis Delta Virus

    PubMed Central

    Tunitskaya, Vera L.; Eliseeva, Olesja V.; Valuev-Elliston, Vladimir T.; Tyurina, Daria A.; Zakirova, Natalia F.; Khomich, Olga A.; Kalis, Martins; Latyshev, Oleg E.; Starodubova, Elizaveta S.; Ivanova, Olga N.; Kochetkov, Sergey N.; Isaguliants, Maria G.; Ivanov, Alexander V.

    2016-01-01

    Hepatitis delta virus (HDV) is a viroid-like blood-borne human pathogen that accompanies hepatitis B virus infection in 5% patients. HDV has been studied for four decades; however, the knowledge on its life-cycle and pathogenesis is still sparse. The studies are hampered by the absence of the commercially-available HDV-specific antibodies. Here, we describe a set of reproducible methods for the expression in E. coli of His-tagged small antigen of HDV (S-HDAg), its purification, and production of polyclonal anti-S-HDAg antibodies in rabbits. S-HDAg was cloned into a commercial vector guiding expression of the recombinant proteins with the C-terminal His-tag. We optimized S-HDAg protein purification procedure circumventing a low affinity of the His-tagged S-HDAg to the Ni-nitrilotriacetyl agarose (Ni-NTA-agarose) resin. Optimization allowed us to obtain S-HDAg with >90% purity. S-HDAg was used to immunize Shinchilla grey rabbits which received 80 μg of S-HDAg in two subcutaneous primes in the complete, followed by four 40 μg boosts in incomplete Freunds adjuvant. Rabbits were bled two weeks post each boost. Antibody titers determined by indirect ELISA exceeded 107. Anti-S-HDAg antibodies detected the antigen on Western blots in the amounts of up-to 100 pg. They were also successfully used to characterize the expression of S-HDAg in the eukaryotic cells by immunofluorescent staining/confocal microscopy. PMID:27775592

  10. Adult Living with Hepatitis B

    MedlinePlus

    ... Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS Coinfection Prevention & ... Institute Education & Training Hep B United Coalition Hepatitis Delta Connect 2017 International HBV Meeting National Patient Advocacy ...

  11. Reduced genetic distance and high replication levels increase the RNA recombination rate of hepatitis delta virus.

    PubMed

    Lin, Chia-Chi; Yang, Zhi-Wei; Iang, Shan-Bei; Chao, Mei

    2015-01-02

    Hepatitis delta virus (HDV) replication is carried out by host RNA polymerases. Since homologous inter-genotypic RNA recombination is known to occur in HDV, possibly via a replication-dependent process, we hypothesized that the degree of sequence homology and the replication level should be related to the recombination frequency in cells co-expressing two HDV sequences. To confirm this, we separately co-transfected cells with three different pairs of HDV genomic RNAs and analyzed the obtained recombinants by RT-PCR followed by restriction fragment length polymorphism and sequencing analyses. The sequence divergence between the clones ranged from 24% to less than 0.1%, and the difference in replication levels was as high as 100-fold. As expected, significant differences were observed in the recombination frequencies, which ranged from 0.5% to 47.5%. Furthermore, varying the relative amounts of parental RNA altered the dominant recombinant species produced, suggesting that template switching occurs frequently during the synthesis of genomic HDV RNA. Taken together, these data suggest that during the host RNA polymerase-driven RNA recombination of HDV, both inter- and intra-genotypic recombination events are important in shaping the genetic diversity of HDV.

  12. [Hepatitis B and delta: the prevalence of seroepidemiological markers in volunteer blood donors and their families].

    PubMed

    Alvarez-Muñoz, M T; Bustamante-Calvillo, M E; Guiscafré-Gallardo, J P; Muñoz, O

    1991-01-01

    41 volunteer blood donors and his relatives were studied in order to know about the prevalence of hepatitis B and D virus infections in selected groups. Frequency of HBsAg+ carriers was 0.34 per cent in the Centro Nacional de la Transfusión Sanguínea and 0.15 per cent in the Banco Central de Sangre, IMSS. Most of the HBsAg+ blood donors were 21 to 40 years old (87.8%); 21.9 per cent had IgM antibodies against HBc and just 2.4 per cent were HBeAg positive. Forty one (26.9%) of 152 relatives had one or more of the HBV markers, 3.9 per cent were HBsAg carriers and 1.3 per cent were HBeAg positive. In the infected relatives group 36.6 per cent were ancestory or brothers and just 14.6 per cent of wives were infected. None of the HBsAg+ blood donors or his relatives had antibodies against delta agent. These results support the fact that the frequency of asymptomatic carriers of HBsAg in the volunteer blood donors group is similar to he frequency in the general population and identifies the group of relatives as those with the highest risk to acquire HBV infection.

  13. Diagnosis of Hepatitis A Virus Infection: a Molecular Approach

    PubMed Central

    Nainan, Omana V.; Xia, Guoliang; Vaughan, Gilberto; Margolis, Harold S.

    2006-01-01

    Current serologic tests provide the foundation for diagnosis of hepatitis A and hepatitis A virus (HAV) infection. Recent advances in methods to identify and characterize nucleic acid markers of viral infections have provided the foundation for the field of molecular epidemiology and increased our knowledge of the molecular biology and epidemiology of HAV. Although HAV is primarily shed in feces, there is a strong viremic phase during infection which has allowed easy access to virus isolates and the use of molecular markers to determine their genetic relatedness. Molecular epidemiologic studies have provided new information on the types and extent of HAV infection and transmission in the United States. In addition, these new diagnostic methods have provided tools for the rapid detection of food-borne HAV transmission and identification of the potential source of the food contamination. PMID:16418523

  14. Influence of delta virus infection on the virologic status in Egyptian patients with chronic hepatitis B virus genotype D.

    PubMed

    Fouad, Rabab; Abdo, Mahmoud; Eldeen, Hadeel Gamal; Sabry, Dina; Atef, Mira; Ahmed, Rasha; Zayed, Naglaa

    2016-05-01

    Hepatitis delta virus (HDV) usually have an unfavorable clinical outcome in chronic hepatitis B virus (HBV) patients. In Egypt, data about epidemiology, the spectrum of disease, and impact of HDV on HBV infection are rare. To assess the prevalence, clinical and virological characteristics of HDV infection among Egyptian patients with chronic HBV. Adult patients with Hepatitis B surface antigen (HBsAg)-positive were evaluated for the presence of HDV using anti HDV-IgG and HDV RNA by RT-PCR. Routine laboratory investigations, genotypes and subtypes for both HBV and HDV, abdominal sonography, and transient elastography (TE) were done. Liver biopsy was performed only in whenever indicated. One hundred and twenty-one treatment-naïve chronic HBV patients were included. Wild HBV genotype-D2 was found in 98.2% and 81.9% were HBeAg negative. Prevalence of HDV was 8.3% by anti-HDV IgG and 9.9% by RT-PCR. Wild HDV genotype-IIb was reported in 83.3%. HDV infection was more common in males, 90.9% of delta patients were HBeAg negative. Compared to the mono-infected HBV, concomitant HBV/HDV infection was not associated with more derangment in ALT nor advanced stage of fibrosis. 66.7% of HDV patients had significantly lower HBV-DNA level compared to the non-delta patients (P < 0.001). HDV is not uncommon in Egypt. HBV genotype-D was associated with HDV genotype-IIb. Delta infection was associated with negative HBeAg status, reduction of HBV replication, but neither influenced the clinical course nor increased significant liver damage risk.

  15. Molecular biology and inhibitors of hepatitis A virus.

    PubMed

    Debing, Yannick; Neyts, Johan; Thibaut, Hendrik Jan

    2014-09-01

    Hepatitis A virus (HAV) is a faeco-orally transmitted picornavirus and is one of the main causes of acute hepatitis worldwide. An overview of the molecular biology of HAV is presented with an emphasis on recent findings. Immune evasion strategies and a possible correlation between HAV and atopy are discussed as well. Despite the availability of efficient vaccines, antiviral drugs targeting HAV are required to treat severe cases of fulminant hepatitis, contain outbreaks, and halt the potential spread of vaccine-escape variants. Additionally, such drugs could be used to shorten the period of illness and decrease associated economical costs. Several known inhibitors of HAV with various mechanisms of action will be discussed. Since none of these molecules is readily useable in the clinic and since the availability of an anti-HAV drug would be of clinical importance, increased efforts should be targeted toward discovery and development of such antivirals.

  16. Hepatitis B (HBV), Hepatitis C (HCV) and Hepatitis Delta (HDV) Viruses in the Colombian Population—How Is the Epidemiological Situation?

    PubMed Central

    Alvarado-Mora, Mónica Viviana; Gutierrez Fernandez, María Fernanda; Gomes-Gouvêa, Michele Soares; de Azevedo Neto, Raymundo Soares; Carrilho, Flair José; Pinho, João Renato Rebello

    2011-01-01

    Background Viral hepatitis B, C and delta still remain a serious problem worldwide. In Colombia, data from 1980s described that HBV and HDV infection are important causes of hepatitis, but little is known about HCV infection. The aim of this study was to determine the currently frequency of HBV, HCV and HDV in four different Colombian regions. Methodology/Principal Findings This study was conducted in 697 habitants from 4 Colombian departments: Amazonas, Chocó, Magdalena and San Andres Islands. Epidemiological data were obtained from an interview applied to each individual aiming to evaluate risk factors related to HBV, HCV or HDV infections. All samples were tested for HBsAg, anti-HBc, anti-HBs and anti-HCV markers. Samples that were positive to HBsAg and/or anti-HBc were tested to anti-HDV. Concerning the geographical origin of the samples, the three HBV markers showed a statistically significant difference: HBsAg (p = 0.033) and anti-HBc (p<0.001) were more frequent in Amazonas and Magdalena departments. Isolated anti-HBs (a marker of previous vaccination) frequencies were: Chocó (53.26%), Amazonas (32.88%), Magdalena (17.0%) and San Andrés (15.33%) - p<0.001. Prevalence of anti-HBc increased with age; HBsAg varied from 1.97 to 8.39% (p = 0.033). Amazonas department showed the highest frequency for anti-HCV marker (5.68%), while the lowest frequency was found in San Andrés Island (0.66%). Anti-HDV was found in 9 (5.20%) out of 173 anti-HBc and/or HBsAg positive samples, 8 of them from the Amazonas region and 1 from them Magdalena department. Conclusions/Significance In conclusion, HBV, HCV and HDV infections are detected throughout Colombia in frequency levels that would place some areas as hyperendemic for HBV, especially those found in Amazonas and Magdalena departments. Novel strategies to increase HBV immunization in the rural population and to strengthen HCV surveillance are reinforced by these results. PMID:21559488

  17. Hepatitis B virus molecular biology and pathogenesis

    PubMed Central

    Lamontagne, R. Jason; Bagga, Sumedha; Bouchard, Michael J.

    2016-01-01

    As obligate intracellular parasites, viruses need a host cell to provide a milieu favorable to viral replication. Consequently, viruses often adopt mechanisms to subvert host cellular signaling processes. While beneficial for the viral replication cycle, virus-induced deregulation of host cellular signaling processes can be detrimental to host cell physiology and can lead to virus-associated pathogenesis, including, for oncogenic viruses, cell transformation and cancer progression. Included among these oncogenic viruses is the hepatitis B virus (HBV). Despite the availability of an HBV vaccine, 350–500 million people worldwide are chronically infected with HBV, and a significant number of these chronically infected individuals will develop hepatocellular carcinoma (HCC). Epidemiological studies indicate that chronic infection with HBV is the leading risk factor for the development of HCC. Globally, HCC is the second highest cause of cancer-associated deaths, underscoring the need for understanding mechanisms that regulate HBV replication and the development of HBV-associated HCC. HBV is the prototype member of the Hepadnaviridae family; members of this family of viruses have a narrow host range and predominately infect hepatocytes in their respective hosts. The extremely small and compact hepadnaviral genome, the unique arrangement of open reading frames, and a replication strategy utilizing reverse transcription of an RNA intermediate to generate the DNA genome are distinguishing features of the Hepadnaviridae. In this review, we provide a comprehensive description of HBV biology, summarize the model systems used for studying HBV infections, and highlight potential mechanisms that link a chronic HBV-infection to the development of HCC. For example, the HBV X protein (HBx), a key regulatory HBV protein that is important for HBV replication, is thought to play a cofactor role in the development of HBV-induced HCC, and we highlight the functions of HBx that may

  18. Hepatitis B virus (HBV) and dual HBV-hepatitis delta virus (HDV) infection in apparently healthy persons.

    PubMed

    Brehar-Cioflec, D; Claici, C; Roşiu, N; Negrea, D A; Moldovan, R; Coşniţă, M

    1998-01-01

    The main aims of the present study were to evaluate the transfusional risk concerning HBV and HBV-HDV infections and the prevalence of viral serum markers in apparently healthy persons. Our study included 226 apparently healthy persons in whom we performed tests for HBV (HBsAg, HBsAb, HBcAb) and HDV (Delta Ab) serum markers, using the enzyme immunoassay. In 45 (19.9%) subjects we detected serum HBsAg. In the 181 HBsAg-negative apparently healthy persons, our tests detected HBsAb (31 subjects) and HBcAb (49 subjects). Thus, 125 (55.3%) of the 226 apparently healthy persons had serologic evidence of past HBV infections. Delta Ab were detected in 3 (1.3%) of our subjects. We must state that one of the three Delta Ab-positive apparently healthy persons tested negative for both HBsAg and HBcAb.

  19. Liver Cancer and Hepatitis B

    MedlinePlus

    ... Our Accomplishments Annual Reports Our Videos 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 ...

  20. Molecular Biology and Infection of Hepatitis E Virus

    PubMed Central

    Nan, Yuchen; Zhang, Yan-Jin

    2016-01-01

    Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus. PMID:27656178

  1. Molecular alterations in hepatocellular carcinoma associated with hepatitis B and hepatitis C infections

    PubMed Central

    Izzo, Francesco; Buonaguro, Franco M.

    2016-01-01

    Chronic infections with hepatitis B (HBV) and hepatitis C viruses (HCV) are the leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. Both viruses encode multifunctional regulatory proteins activating several oncogenic pathways, which induce accumulation of multiple genetic alterations in the infected hepatocytes. Gene mutations in HBV- and HCV-induced HCCs frequently impair the TP53, Wnt/b-catenin, RAS/RAF/MAPK kinase and AKT/mTOR pathways, which represent important anti-cancer targets. In this review, we highlight the molecular mechanisms underlying the pathogenesis of primary liver cancer, with particular emphasis on the host genetic variations identified by high-throughput technologies. In addition, we discuss the importance of genetic alterations, such as mutations in the telomerase reverse transcriptase (TERT) promoter, for the diagnosis, prognosis, and tumor stratification for development of more effective treatment approaches. PMID:26943571

  2. Cellular Nuclear Export Factors TAP and Aly Are Required for HDAg-L-mediated Assembly of Hepatitis Delta Virus.

    PubMed

    Huang, Hsiu-Chen; Lee, Chung-Pei; Liu, Hui-Kang; Chang, Ming-Fu; Lai, Yu-Heng; Lee, Yu-Ching; Huang, Cheng

    2016-12-09

    Hepatitis delta virus (HDV) is a satellite virus of hepatitis B virus (HBV). HDV genome encodes two forms of hepatitis delta antigen (HDAg), small HDAg (HDAg-S), which is required for viral replication, and large HDAg (HDAg-L), which is essential for viral assembly. HDAg-L is identical to HDAg-S except that it bears a 19-amino acid extension at the C terminus. Both HDAgs contain a nuclear localization signal (NLS), but only HDAg-L contains a CRM1-independent nuclear export signal at its C terminus. The nuclear export activity of HDAg-L is important for HDV particle formation. However, the mechanisms of HDAg-L-mediated nuclear export of HDV ribonucleoprotein are not clear. In this study, the host cellular RNA export complex TAP-Aly was found to form a complex with HDAg-L, but not with an export-defective HDAg-L mutant, in which Pro(205) was replaced by Ala. HDAg-L was found to colocalize with TAP and Aly in the nucleus. The C-terminal domain of HDAg-L was shown to directly interact with the N terminus of TAP, whereas an HDAg-L mutant lacking the NLS failed to interact with full-length TAP. In addition, small hairpin RNA-mediated down-regulation of TAP or Aly reduced nuclear export of HDAg-L and assembly of HDV virions. Furthermore, a peptide, TAT-HDAg-L(198-210), containing the 10-amino acid TAT peptide and HDAg-L(198-210), inhibited the interaction between HDAg-L and TAP and blocked HDV virion assembly and secretion. These data demonstrate that formation and release of HDV particles are mediated by TAP and Aly.

  3. The application of hepatic P450 reductase null gpt delta mice in studying the role of hepatic P450 in genotoxic carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced mutagenesis.

    PubMed

    Luan, Yang; Xing, Guozhen; Qi, Xinming; Wu, Mengjun; Li, Chenggang; Yao, Jun; Gong, Likun; Nohmi, Takehiko; Gu, Jun; Zhou, Wanhong; Zheng, Saijing; Ren, Jin

    2012-11-01

    The cytochrome P450 (P450 or CYP) is involved in both detoxification and metabolic activation of many carcinogens. In order to identify the role of hepatic P450 in the mutagenesis of genotoxic carcinogens, we generated a novel hepatic P450 reductase null (HRN) gpt delta mouse model, which lacks functional hepatic P450 on a gpt delta mouse background. In this study, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was used to treat HRN gpt delta mice and control littermates. Gene mutations in the liver and lungs were detected, and mutation spectra were analyzed. Pharmacokinetic analyses were performed, and tissue levels of NNK and metabolite were determined. NNK-induced mutant frequencies (MFs) were equivalent to spontaneous MFs in the liver, but increased more than 3 times in the lungs of HRN gpt delta mice compared to control mice. NNK-induced mutation spectra showed no difference between HRN gpt delta mice and control littermates. Toxicokinetic studies revealed reduced clearance of NNK with elevated tissue concentrations in HRN gpt delta mice. To our knowledge, these are the first data demonstrating that NNK cannot induce mutagenesis in the liver without P450 metabolic activation, but can induce mutagenesis in lungs by a hepatic P450-independent mechanism. Moreover, our data show that hepatic P450 plays a major role in the systemic clearance of NNK, thereby protecting the lungs against NNK-induced mutagenesis. Our model will be useful in establishing the role of hepatic versus extrahepatic P450-mediated mutagenesis, and the relative contributions of P450 compared to other biotransformation enzymes in the genotoxic carcinogens' activation.

  4. Hepatitis A virus: host interactions, molecular epidemiology and evolution.

    PubMed

    Vaughan, Gilberto; Goncalves Rossi, Livia Maria; Forbi, Joseph C; de Paula, Vanessa S; Purdy, Michael A; Xia, Guoliang; Khudyakov, Yury E

    2014-01-01

    Infection with hepatitis A virus (HAV) is the commonest viral cause of liver disease and presents an important public health problem worldwide. Several unique HAV properties and molecular mechanisms of its interaction with host were recently discovered and should aid in clarifying the pathogenesis of hepatitis A. Genetic characterization of HAV strains have resulted in the identification of different genotypes and subtypes, which exhibit a characteristic worldwide distribution. Shifts in HAV endemicity occurring in different parts of the world, introduction of genetically diverse strains from geographically distant regions, genotype displacement observed in some countries and population expansion detected in the last decades of the 20th century using phylogenetic analysis are important factors contributing to the complex dynamics of HAV infections worldwide. Strong selection pressures, some of which, like usage of deoptimized codons, are unique to HAV, limit genetic variability of the virus. Analysis of subgenomic regions has been proven useful for outbreak investigations. However, sharing short sequences among epidemiologically unrelated strains indicates that specific identification of HAV strains for molecular surveillance can be achieved only using whole-genome sequences. Here, we present up-to-date information on the HAV molecular epidemiology and evolution, and highlight the most relevant features of the HAV-host interactions.

  5. Recent advances in molecular diagnostics of hepatitis B virus.

    PubMed

    Datta, Sibnarayan; Chatterjee, Soumya; Veer, Vijay

    2014-10-28

    Hepatitis B virus (HBV) is one of the important global health problems today. Infection with HBV can lead to a variety of clinical manifestations including severe hepatic complications like liver cirrhosis and hepatocellular carcinoma. Presently, routine HBV screening and diagnosis is primarily based on the immuno-detection of HBV surface antigen (HBsAg). However, identification of HBV DNA positive cases, who do not have detectable HBsAg has greatly encouraged the use of nucleic acid amplification based assays, that are highly sensitive, specific and are to some extent tolerant to sequence variation. In the last few years, the field of HBV molecular diagnostics has evolved rapidly with advancements in the molecular biology tools, such as polymerase chain reaction (PCR) and real-time PCR. Recently, apart of PCR based amplification methods, a number of isothermal amplification assays, such as loop mediated isothermal amplification, transcription mediated amplification, ligase chain reaction, and rolling circle amplification have been utilized for HBV diagnosis. These assays also offer options for real time detection and integration into biosensing devices. In this manuscript, we review the molecular technologies that are presently available for HBV diagnostics, with special emphasis on isothermal amplification based technologies. We have also included the recent trends in the development of biosensors and use of next generation sequencing technologies for HBV.

  6. Architecture of coatomer: molecular characterization of delta-COP and protein interactions within the complex

    PubMed Central

    1996-01-01

    Coatomer is a cytosolic protein complex that forms the coat of COP I- coated transport vesicles. In our attempt to analyze the physical and functional interactions between its seven subunits (coat proteins, [COPs] alpha-zeta), we engaged in a program to clone and characterize the individual coatomer subunits. We have now cloned, sequenced, and overexpressed bovine alpha-COP, the 135-kD subunit of coatomer as well as delta-COP, the 57-kD subunit and have identified a yeast homolog of delta-COP by cDNA sequence comparison and by NH2-terminal peptide sequencing. delta-COP shows homologies to subunits of the clathrin adaptor complexes AP1 and AP2. We show that in Golgi-enriched membrane fractions, the protein is predominantly found in COP I-coated transport vesicles and in the budding regions of the Golgi membranes. A knock-out of the delta-COP gene in yeast is lethal. Immunoprecipitation, as well as analysis exploiting the two-hybrid system in a complete COP screen, showed physical interactions between alpha- and epsilon-COPs and between beta- and delta-COPs. Moreover, the two-hybrid system indicates interactions between gamma- and zeta-COPs as well as between alpha- and beta' COPs. We propose that these interactions reflect in vivo associations of those subunits and thus play a functional role in the assembly of coatomer and/or serve to maintain the molecular architecture of the complex. PMID:8858162

  7. The human RNA polymerase II interacts with the terminal stem-loop regions of the hepatitis delta virus RNA genome

    SciTech Connect

    Greco-Stewart, Valerie S.; Miron, Paul; Abrahem, Abrahem; Pelchat, Martin . E-mail: mpelchat@uottawa.ca

    2007-01-05

    The hepatitis delta virus (HDV) is an RNA virus that depends on DNA-dependent RNA polymerase (RNAP) for its transcription and replication. While it is generally accepted that RNAP II is involved in HDV replication, its interaction with HDV RNA requires confirmation. A monoclonal antibody specific to the carboxy terminal domain of the largest subunit of RNAP II was used to establish the association of RNAP II with both polarities of HDV RNA in HeLa cells. Co-immunoprecipitations using HeLa nuclear extract revealed that RNAP II interacts with HDV-derived RNAs at sites located within the terminal stem-loop domains of both polarities of HDV RNA. Analysis of these regions revealed a strong selection to maintain a rod-like conformation and demonstrated several conserved features. These results provide the first direct evidence of an association between human RNAP II and HDV RNA and suggest two transcription start sites on both polarities of HDV RNA.

  8. Hepatitis

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Hepatitis KidsHealth > For Teens > Hepatitis Print A A A ... to a liver condition called hepatitis . What Is Hepatitis? The liver is one of the body's powerhouses. ...

  9. Hepatitis

    MedlinePlus

    ... de los dientes Video: Getting an X-ray Hepatitis KidsHealth > For Kids > Hepatitis Print A A A ... an important digestive liquid called bile . What Is Hepatitis? Hepatitis is an inflammation (say: in-fluh-MAY- ...

  10. delta-Aminolevulinate dehydratase inhibition by ascorbic acid is mediated by an oxidation system existing in the hepatic supernatant.

    PubMed

    Beber, F A; Wollmeister, J; Brigo, M J; Silva, M C; Pereira, C N; Rocha, J B

    1998-01-01

    The effect of ascorbic acid (AA) on hepatic delta-aminolevulinic acid dehydratase (ALA-D) activity was studied. AA decreased enzyme activity by reducing maximum velocity and tended to increase the Michaelis constant. ALA-D inactivation by AA occurred similarly both in air and argonium atmosphere incubation. DTT reduced considerably the inhibitory effect of AA on ALA-D, but glutathione was ineffective in reversing inactivation. These data indicate that inhibition occurs mainly due to an acceleration of the oxidation rate mediated by the hepatic supernatant utilizing AA in sulfhydryl groups of cysteine residues present at the ALA-D active site. AA probably acts on cysteine from the ALA-D B site since cucumber and radish leaves ALA-D was not inhibited by AA (up to 16 mM). The addition of free radical scavengers to the medium did not alter ALA-D inactivation caused by AA, indicating that active oxygen species formed during AA oxidation were not directly related to -SH oxidation. The chelation of zinc ions from the enzyme by EDTA turned ALA-D more susceptible to the inhibitory effect of AA. This effect seems to involve mainly ZnB, which is known to bind to four cysteines. The present data suggest that AA may participate in the regulation of the heme biosynthesis pathway by promoting a reversible inactivation of ALA-D.

  11. Efficient Hepatitis Delta Virus RNA Replication in Avian Cells Requires a Permissive Factor(s) from Mammalian Cells

    PubMed Central

    Liu, Yu-Tsueng; Brazas, Rob; Ganem, Don

    2001-01-01

    Hepatitis delta virus (HDV) is a highly pathogenic human RNA virus whose genome is structurally related to those of plant viroids. Although its spread from cell to cell requires helper functions supplied by hepatitis B virus (HBV), intracellular HDV RNA replication can proceed in the absence of HBV proteins. As HDV encodes no RNA-dependent RNA polymerase, the identity of the (presumably cellular) enzyme responsible for this reaction remains unknown. Here we show that, in contrast to mammalian cells, avian cells do not support efficient HDV RNA replication and that this defect cannot be rescued by provision of HDV gene products in trans. Contrary to earlier assertions, this defect is not due to enhanced apoptosis triggered in avian cells by HDV. Fusion of avian cells to mammalian cells rescues HDV replication in avian nuclei, indicating that the nonpermissive phenotype of avian cells is not due to the presence of dominantly acting inhibitors of replication. Rather, avian cells lack one or more essential permissive factors present in mammalian cells. These results set the stage for the identification of such factors and also explain the failure of earlier efforts to transmit HDV infection to avian hosts harboring indigenous hepadnaviruses. PMID:11462021

  12. Molecular epidemiology of hepatitis A virus infection in Northeast India.

    PubMed

    Bose, Moumita; Bose, Sujoy; Saikia, Anjan; Medhi, Subhash; Deka, Manab

    2015-07-01

    The present study was undertaken to screen the molecular epidemiology of Hepatitis A virus (HAV) in Northeast India (NEI) who are ethnically distinct, tribal dominated and of lower socio-economic status with almost no information available from NEI on these aspects. Briefly, 3 ml blood was collected from 324 random liver disease cases with jaundice, receiving care at Central Hospital, N.F. Railway, Guwahati, Assam with informed consent. The patients detected with HAV-IgM positive status were included and were stratified as acute viral hepatitis (AVH) and fulminant hepatitis (FHF) based on clinical profile. Viral RNA was isolated and HAV-RNA was detected by Real-time PCR using primers for the VP3-VP1 region. HAV genotyping was studied by PCR-direct sequencing-phylogenetic analysis approach using the VP1/2A region of HAV isolates. Statistical analysis was performed using SPSS13.0 software. A total of 69 cases were HAV infected with two HBV co-infected cases (n = 69 + 2 = 71), 62 cases and two co-infected cases were AVH and others were FHF cases. HAV infection was predominant in especially in the young and adult age group. HAV-RNA was detected in 28 cases, out of which 19 cases could be genotyped (12 AVH, 7 FHF); which showed the prevalence of genotype IIIA or IA only. Although HAV genotype IIIA was the major genotype in both the AVH (10/12, 83.33%) and FHF (5/7, 71.43%) group, but the difference in distribution of genotypes in AVH and FHF cases was statistically non-significant (P = 0.550). HAV genotype IIIA is associated with the majority of HAV infected cases and severity in NEI.

  13. [Molecular basis of obesity-related hepatic steatosis].

    PubMed

    Buqué, X; Aspichueta, P; Ochoa, B

    2008-09-01

    Non-alcoholic fatty liver disease is a chronic inflammation liver condition that is currently highly relevant because of its strong association with increasingly incident diseases such as obesity and type-2 diabetes mellitus. The primary purpose of this paper is to discuss the best part of current knowledge on the molecular mechanisms involved in hepatic steatosis development, the condition s initial stage, and on progression to steatohepatitis. Special attention has been paid to clinical and experimental obesity-related fatty liver. In the latter, the fa/fa rat is assessed, which constitutes an animal model for obesity with phenotype features similar to human obesity, including insulin resistance and dyslipemia. Hepatic steatosis is a complex, mainly metabolic condition where apparently non-compatible metabolic processes concur, in addition to oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and decreased expression of survival genes. Extrahepatic signals underlie the disorder, such as those arising from peripheral insulin resistance associated with an increase in adipose mass and systemic free fatty acids, together with intrahepatic signals leading to derangement of liver glycostatic and lipidostatic functions, as well as to greater vulnerability to other aggressions.

  14. Molecular mechanisms of hepatitis C virus-induced hepatocellular carcinoma.

    PubMed

    Vescovo, T; Refolo, G; Vitagliano, G; Fimia, G M; Piacentini, M

    2016-10-01

    Hepatitis C virus (HCV) is a major leading cause of hepatocellular carcinoma (HCC). HCV-induced hepatocarcinogenesis is a multistep process resulting from a combination of pathway alterations that are either caused directly by viral factors or immune mediated as a consequence of a chronic state of inflammation. Host genetic variation is now emerging as an additional element that contribute to increase the risk of developing HCC. The advent of direct-acting antiviral agents foresees a rapid decline of HCC rate in HCV patients. However, a full understanding of the HCV-mediated tumourigenic process is required to elucidate if pro-oncogenic signatures may persist after virus clearance, and to identify novel tools for HCC prevention and therapy. In this review, we summarize the current knowledge of the molecular mechanisms responsible for HCV-induced hepatocarcinogenesis.

  15. Hepatitis B Foundation Newsletter: B Informed

    MedlinePlus

    ... Our Accomplishments Annual Reports Our Videos 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 ...

  16. Hepatitis

    MedlinePlus

    ... clotting problems or chronic liver disease. previous continue Hepatitis B and Hepatitis C Although hep A is a ... does — through direct contact with infected body fluids. Hepatitis B and C are even more easily passed in ...

  17. Hepatitis

    MedlinePlus

    ... A if they've been vaccinated against it. Hepatitis B Hepatitis B is a more serious infection. It may lead ... of which cause severe illness and even death. Hepatitis B virus (HBV) is transmitted from person to person ...

  18. Hepatitis

    MedlinePlus

    ... Issues Listen Español Text Size Email Print Share Hepatitis Page Content Article Body Hepatitis means “inflammation of ... it has been associated with drinking contaminated water. Hepatitis Viruses Type Transmission Prognosis A Fecal-oral (stool ...

  19. Continuous expression and replication of the hepatitis delta virus genome in Hep G2 hepatoblastoma cells transfected with cloned viral DNA.

    PubMed Central

    Chen, P J; Kuo, M Y; Chen, M L; Tu, S J; Chiu, M N; Wu, H L; Hsu, H C; Chen, D S

    1990-01-01

    To establish stable cell clones allowing continuous replication of hepatitis delta virus (HDV), Hep G2, a hepatoblastoma cell line containing no hepatitis B virus (HBV) DNA sequences, was transfected with a recombinant plasmid containing a tandem trimer of HDV cDNA (driven by the simian virus 40 late promoter) and a neomycin-resistance gene. After selection with the neomycin analogue G418, at least two of the resistant clones were shown to have intact delta antigen by specific immunoblotting, and the delta antigen was located in the cell nucleus by immunofluorescence. Transfected cloned viral DNAs were found to be integrated into cell chromosomes. Replication of the HDV genome was demonstrated by the presence of not only genomic and antigenomic HDV RNAs but also HDV RNAs in multimeric and circular forms. In addition, a 0.8-kilobase antigenomic RNA containing a poly(A) tail and encoding the delta-antigen open reading frame was documented. Continuous replication and transcription of the HDV genome was thus achieved in these transfected cell lines. The results confirmed that replication of HDV was unassisted by HBV. Stable passage of such cell lines strongly suggests that HDV lacks direct cytopathicity in hepatocytes. These clones should be useful in studying the details of the HDV life cycle and the relationship between HDV and its helper virus, HBV. Images PMID:2164671

  20. Molecular Testing in the Diagnosis and Management of Chronic Hepatitis B

    PubMed Central

    Valsamakis, Alexandra

    2007-01-01

    Hepatitis B virus (HBV) is an enveloped virus with a small (3.2-kb) partially double-stranded DNA genome that causes acute and chronic infections. The impact of these infections on public health worldwide is enormous, with an estimated prevalence of 2 billion acute infections and 360 million chronic infections globally. This review focuses on chronic hepatitis B and the molecular assays used in its diagnosis and management. Background information, including that about features of the hepatitis B virion, viral replication, and epidemiology of infection, that is important for understanding chronic hepatitis B and molecular diagnostic tests for HBV is provided. To facilitate an understanding of the utility of molecular testing for chronic hepatitis B, the four stages of chronic hepatitis B infection that are currently recognized, as well as an additional entity, occult hepatitis B, that can be diagnosed only by sensitive nucleic acid amplification methods, are reviewed in detail, including available therapeutic agents. The molecular diagnostic content focuses on tests for HBV DNA quantification, genotyping, and mutation detection (including precore/core promoter and antiviral resistance mutations). The discussion of these tests encompasses their current utility and performance characteristics, drawing from current clinical guidelines and other studies from the literature. In recognition of the continual evolution of this field, the final section describes emerging molecular markers with future diagnostic potential. PMID:17630333

  1. Binding of the polypyrimidine tract-binding protein-associated splicing factor (PSF) to the hepatitis delta virus RNA

    SciTech Connect

    Greco-Stewart, Valerie S.; Thibault, Catherine St-Laurent; Pelchat, Martin . E-mail: mpelchat@uottawa.ca

    2006-12-20

    The hepatitis delta virus (HDV) has a very limited protein coding capacity and must rely on host proteins for its replication. A ribonucleoprotein complex was detected following UV cross-linking between HeLa nuclear proteins and an RNA corresponding to the right terminal stem-loop domain of HDV genomic RNA. Mass spectrometric analysis of the complex revealed the polypyrimidine tract-binding protein-associated splicing factor (PSF) as a novel HDV RNA-interacting protein. Co-immunoprecipitation demonstrated the interaction between HDV RNA and PSF both in vitro in HeLa nuclear extract and in vivo within HeLa cells containing both polarities of the HDV genome. Analysis of the binding of various HDV-derived RNAs to purified, recombinant PSF further confirmed the specificity of the interaction and revealed that PSF directly binds to the terminal stem-loop domains of both polarities of HDV RNA. Our findings provide evidence of the involvement of a host mRNA processing protein in the HDV life cycle.

  2. Inverse Thio Effects in the Hepatitis Delta Virus Ribozyme Reveal that the Reaction Pathway Is Controlled by Metal Ion Charge Density

    PubMed Central

    2015-01-01

    The hepatitis delta virus (HDV) ribozyme self-cleaves in the presence of a wide range of monovalent and divalent ions. Prior theoretical studies provided evidence that self-cleavage proceeds via a concerted or stepwise pathway, with the outcome dictated by the valency of the metal ion. In the present study, we measure stereospecific thio effects at the nonbridging oxygens of the scissile phosphate under a wide range of experimental conditions, including varying concentrations of diverse monovalent and divalent ions, and combine these with quantum mechanical/molecular mechanical (QM/MM) free energy simulations on the stereospecific thio substrates. The RP substrate gives large normal thio effects in the presence of all monovalent ions. The SP substrate also gives normal or no thio effects, but only for smaller monovalent and divalent cations, such as Li+, Mg2+, Ca2+, and Sr2+; in contrast, sizable inverse thio effects are found for larger monovalent and divalent cations, including Na+, K+, NH4+, and Ba2+. Proton inventories are found to be unity in the presence of the larger monovalent and divalent ions, but two in the presence of Mg2+. Additionally, rate–pH profiles are inverted for the low charge density ions, and only imidazole plus ammonium ions rescue an inactive C75Δ variant in the absence of Mg2+. Results from the thio effect experiments, rate–pH profiles, proton inventories, and ammonium/imidazole rescue experiments, combined with QM/MM free energy simulations, support a change in the mechanism of HDV ribozyme self-cleavage from concerted and metal ion-stabilized to stepwise and proton transfer-stabilized as the charge density of the metal ion decreases. PMID:25799319

  3. General Base Catalysis for Cleavage by the Active-Site Cytosine of the Hepatitis Delta Virus Ribozyme: QM/MM Calculations Establish Chemical Feasibility

    PubMed Central

    Banáš, Pavel; Rulíšek, Lubomír; Hánošová, Veronika; Svozil, Daniel; Walter, Nils G.

    2008-01-01

    The hepatitis delta virus (HDV) ribozyme is an RNA motif embedded in human pathogenic HDV RNA. Previous experimental studies have established that the active-site nucleotide C75 is essential for self-cleavage of the ribozyme, although its exact catalytic role in the process remains debated. Structural data from X-ray crystallography generally indicate that C75 acts as the general base that initiates catalysis by deprotonating the 2′-OH nucleophile at the cleavage site, while a hydrated magnesium ion likely protonates the 5′-oxygen leaving group. In contrast, some mechanistic studies support the role of C75 acting as general acid and thus being protonated before the reaction. We report combined quantum chemical/molecular mechanical calculations for the C75 general base pathway, utilizing the available structural data for the wild type HDV genomic ribozyme as a starting point. Several starting configurations differing in magnesium ion placement were considered and both one-dimensional and two-dimensional potential energy surface scans were used to explore plausible reaction paths. Our calculations show that C75 is readily capable of acting as the general base, in concert with the hydrated magnesium ion as the general acid. We identify a most likely position for the magnesium ion, which also suggests it acts as a Lewis acid. The calculated energy barrier of the proposed mechanism, ~20 kcal/mol, would lower the reaction barrier by ~15 kcal/mol compared to the uncatalyzed reaction and is in good agreement with experimental data. PMID:18686993

  4. Molecular epidemiology of hepatitis B virus in Misiones, Argentina.

    PubMed

    Mojsiejczuk, Laura Noelia; Torres, Carolina; Sevic, Ina; Badano, Inés; Malan, Richard; Flichman, Diego Martin; Liotta, Domingo Javier; Campos, Rodolfo Hector

    2016-10-01

    Hepatitis B virus (HBV) infection is a major public health problem worldwide. The aims of this study were to describe the molecular epidemiology of HBV in the Province of Misiones, Argentina and estimate the phylodynamic of the main groups in a Bayesian coalescent framework. To this end, partial or complete genome sequences were obtained from 52 blood donor candidates. The phylogenetic analysis based on partial sequences of S/P region showed a predominance of genotype D (65.4%), followed by genotype F (30.8%) and genotype A as a minority (3.8%). At subgenotype level, the circulation of subgenotypes D3 (42.3%), D2 (13.5%), F1b (11.5%) and F4 (9.6%) was mainly identified. The Bayesian coalescent analysis of 29 complete genome sequences for the main groups revealed that the subgenotypes D2 and D3 had several introductions to the region, with ancestors dating back from 1921 to 1969 and diversification events until the late '70s. The genotype F in Misiones has a more recent history; subgenotype F4 isolates were intermixed with sequences from Argentina and neighboring countries and only one significant cluster dated back in 1994 was observed. Subgenotype F1b isolates exhibited low genetic distance and formed a closely related monophyletic cluster, suggesting a very recent introduction. In conclusion, the phylogenetic and coalescent analyses showed that the European genotype D has a higher circulation, a longer history of diversification and may be responsible for the largest proportion of chronic HBV infections in the Province of Misiones. Genotype F, especially subgenotype F1b, had a more recent introduction and its diversification in the last 20years might be related to its involvement in new transmission events.

  5. Molecular Biology of the Hepatitis B Virus for Clinicians

    PubMed Central

    Datta, Sibnarayan; Chatterjee, Soumya; Veer, Vijay; Chakravarty, Runu

    2012-01-01

    Hepatitis B virus (HBV) infection is one of the major global health problems, especially in economically under-developed or developing countries. HBV infection can lead to a number of clinical outcomes including chronic infection, cirrhosis and liver cancer. It ranks among the top 10 causes of death, being responsible for around 1 million deaths every year. Despite the availability of a highly efficient vaccine and potent antiviral agents, HBV infection still remains a significant clinical problem, particularly in those high endemicity areas where vaccination of large populations has not been possible due to economic reasons. Although HBV is among the smallest viruses in terms of virion and genome size, it has numerous unique features that make it completely distinct from other DNA viruses. It has a partially double stranded DNA with highly complex genome organization, life cycle and natural history. Remarkably distinct from other DNA viruses, it uses an RNA intermediate called pregenomic RNA (pgRNA) and reverse transcriptase for its genome replication. Genome replication is accomplished by a complex mechanism of primer shifting facilitated by direct repeat sequences encoded in the genome. Further, the genome has evolved in such a manner that every single nucleotide of the genome is used for either coding viral proteins or used as regulatory regions or both. Moreover, it utilizes internal in-frame translation initiation codons, as well as different reading frames from the same RNA to generate different proteins with diverse functions. HBV also shows considerable genetic variability which has been related with clinical outcomes, replication potential, therapeutic response etc. This review aims at reviewing fundamental events of the viral life cycle including viral replication, transcription and translation, from the molecular standpoint, as well as, highlights the clinical relevance of genetic variability of HBV. PMID:25755457

  6. Molecular and morphological characterization of myxozoan actinospore types from a commercial catfish pond in the Mississippi Delta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The actinospore diversity of infected Dero digitata was surveyed (May, 2011) from a channel catfish production pond in the Mississippi Delta region for the elucidation of unknown myxozoan life cycles. Only two myxozoan life cycles have been molecularly confirmed in channel catfish (Ictalurus puncta...

  7. Pharmacophore modeling, in silico screening, molecular docking and molecular dynamics approaches for potential alpha-delta bungarotoxin-4 inhibitors discovery

    PubMed Central

    Kumar, R. Barani; Suresh, M. Xavier; Priya, B. Shanmuga

    2015-01-01

    Background: The alpha-delta bungartoxin-4 (α-δ-Bgt-4) is a potent neurotoxin produced by highly venomous snake species, Bungarus caeruleus, mainly targeting neuronal acetylcholine receptors (nAchRs) and producing adverse biological malfunctions leading to respiratory paralysis and mortality. Objective: In this study, we predicted the three-dimensional structure of α-δ-Bgt-4 using homology modeling and investigated the conformational changes and the key residues responsible for nAchRs inhibiting activity. Materials and Methods: From the selected plants, which are traditionally used for snake bites, the active compounds are taken and performed molecular interaction studies and also used for modern techniques like pharmacophore modeling and mapping and absorption, distribution, metabolism, elimination and toxicity analysis which may increase the possibility of success. Results: Moreover, 100's of drug-like compounds were retrieved and analyzed through computational virtual screening and allowed for pharmacokinetic profiling, molecular docking and dynamics simulation. Conclusion: Finally the top five drug-like compounds having competing level of inhibition toward α-δ-Bgt-4 toxin were suggested based on their interaction with α-δ-Bgt-4 toxin. PMID:26109766

  8. Comparative Investigation of Normal Modes and Molecular Dynamics of Hepatitis C NS5B Protein

    NASA Astrophysics Data System (ADS)

    Asafi, M. S.; Yildirim, A.; Tekpinar, M.

    2016-04-01

    Understanding dynamics of proteins has many practical implications in terms of finding a cure for many protein related diseases. Normal mode analysis and molecular dynamics methods are widely used physics-based computational methods for investigating dynamics of proteins. In this work, we studied dynamics of Hepatitis C NS5B protein with molecular dynamics and normal mode analysis. Principal components obtained from a 100 nanoseconds molecular dynamics simulation show good overlaps with normal modes calculated with a coarse-grained elastic network model. Coarse-grained normal mode analysis takes at least an order of magnitude shorter time. Encouraged by this good overlaps and short computation times, we analyzed further low frequency normal modes of Hepatitis C NS5B. Motion directions and average spatial fluctuations have been analyzed in detail. Finally, biological implications of these motions in drug design efforts against Hepatitis C infections have been elaborated.

  9. DEVELOPMENT OF A MOLECULAR METHOD TO IDENTIFY HEPATITIS E VIRUS

    EPA Science Inventory

    Hepatitis E virus (HEV) is a waterborne emerging pathogen that causes significant illness in the developing world. Thus far, an HEV outbreak has not been reported in the U.S., although a swine variant of the virus is common in Midwestern hogs. Because viruses isolated from two ...

  10. Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to mediate the CRM1-independent nuclear export of large hepatitis delta antigen.

    PubMed

    Huang, Cheng; Jiang, Jia-Yin; Chang, Shin C; Tsay, Yeou-Guang; Chen, Mei-Ru; Chang, Ming-Fu

    2013-02-01

    Nuclear export is an important process that not only regulates the functions of cellular factors but also facilitates the assembly of viral nucleoprotein complexes. Chromosome region maintenance 1 (CRM1) that mediates the transport of proteins bearing the classical leucine-rich nuclear export signal (NES) is the best-characterized nuclear export receptor. Recently, several CRM1-independent nuclear export pathways were also identified. The nuclear export of the large form of hepatitis delta antigen (HDAg-L), a nucleocapsid protein of hepatitis delta virus (HDV), which contains a CRM1-independent proline-rich NES, is mediated by the host NES-interacting protein (NESI). The mechanism of the NESI protein in mediating nuclear export is still unknown. In this study, NESI was characterized as a highly glycosylated membrane protein. It interacted and colocalized well in the nuclear envelope with lamin A/C and nucleoporins. Importantly, HDAg-L could be coimmunoprecipitated with lamin A/C and nucleoporins. In addition, binding of the cargo HDAg-L to the C terminus of NESI was detected for the wild-type protein but not for the nuclear export-defective HDAg-L carrying a P205A mutation [HDAg-L(P205A)]. Knockdown of lamin A/C effectively reduced the nuclear export of HDAg-L and the assembly of HDV. These data indicate that by forming complexes with lamin A/C and nucleoporins, NESI facilitates the CRM1-independent nuclear export of HDAg-L.

  11. Crystallization and X-ray diffraction analysis of the Trp/amber editing site of hepatitis delta virus (+)RNA: a case of rational design

    SciTech Connect

    MacElrevey, Celeste; Wedekind, Joseph E.

    2005-12-01

    Well diffracting decamer crystals of the hepatitis delta virus RNA-editing site were prepared, but exhibited merohedral twinning and base averaging owing to duplex symmetry. A longer asymmetric construct that includes additional flanking RNA sequences has been crystallized that does not appear to exhibit these defects. RNA editing by mammalian ADAR1 (Adenosine Deaminase Acting on RNA) is required for the life cycle of the hepatitis delta virus (HDV). Editing extends the single viral open reading frame to yield two protein products of alternate length. ADARs are believed to recognize double-stranded RNA substrates via a ‘structure-based’ readout mechanism. Crystals of 10-mer duplexes representing the HDV RNA-editing site diffracted to 1.35 Å resolution, but suffered from merohedral twinning and averaging of the base registry. Expansion of the construct to include two flanking 3 × 1 internal loops yielded crystals in the primitive tetragonal space group P4{sub 1}2{sub 1}2 or P4{sub 3}2{sub 1}2. X-ray diffraction data were collected to 2.8 Å resolution, revealing a unit cell with parameters a = 62.5, c = 63.5 Å. The crystallization and X-ray analysis of multiple forms of the HDV RNA-editing substrate, encounters with common RNA crystal-growth defects and a strategy to overcome these problems are reported.

  12. Molecular characterization of hepatitis E virus in patients with acute hepatitis in Venezuela.

    PubMed

    García, Cristina Gutiérrez; Sánchez, Doneyla; Villalba, Maria Caridad Montalvo; Pujol, Flor Helene; de Los Ángeles Rodríguez Lay, Licel; Pinto, Belquis; Chacón, Elsa Patricia; Guzmán, Maria Guadalupe

    2012-07-01

    Hepatitis E virus (HEV) causes a common infection in developing countries. HEV infection occurs as outbreaks, as sporadic clinical cases and as large epidemics in endemic areas. The objective of this study was to determine the presence of HEV infection in patients with clinical suspicion of hepatitis A virus (HAV) infection, referred to the Instituto Nacional de Higiene "Rafael Rangel" in Venezuela. Seventy-four sera were tested for anti-HAV and anti-HEV IgM antibodies. HEV-RNA was amplified from anti-HEV IgM positive sera using nested reverse transcription polymerase chain reaction for ORF1 (RNA dependent RNA polymerase region) and the amplicons sequenced for phylogenetic analysis. The frequency of anti-HEV IgM was 22/74 (30%) in the samples tested. Dual infection with HAV and HEV was found in 31% (12/39) of anti-HAV IgM positive patients. Viremia was detected in 3/22 (14%) of sera positive for anti-HEV IgM. Two HEV strains were classified as genotype 1 and one as genotype 3, which were closely related to Yam 67 (north of India) and US1 isolates from the USA, respectively. These findings suggest that HEV is an important cause of acute viral hepatitis in Venezuela as a single infection or co-infection with HAV, with high morbidity in children and young adults suggesting that this infection is endemic in Venezuela.

  13. Association of heterocellular HPFH, beta(+)-thalassaemia, and delta beta(0)-thalassaemia: haematological and molecular aspects.

    PubMed Central

    Cianetti, L; Care, A; Sposi, N M; Giampaolo, A; Calandrini, M; Petrini, M; Massa, A; Marinucci, M; Mavilio, F; Ceccanti, M

    1984-01-01

    An Italian family in which heterocellular hereditary persistence of fetal haemoglobin (HPFH) interacts with both beta(+)- and delta beta-thalassaemia is described. The index case was an 8 year old girl who was presumed to inherit both heterocellular HPFH and beta (+)-thalassaemia from her mother and delta beta-thalassaemia from her father. She was healthy and never needed blood transfusions. The possible contribution of heterocellular HPFH to the less severe expression of the compound delta beta/beta(+)-thalassaemia heterozygosity is discussed. By DNA analysis the specific delta beta-thalassaemia defect on the gamma delta beta globin gene region has been established. In addition, a previously unreported association of a polymorphic restriction site haplotype with a beta (+)-thalassaemia mutation has been observed. PMID:6208362

  14. Molecular Epidemiology of Hepatitis B Virus Variants in Nonhuman Primates

    PubMed Central

    Grethe, Stefanie; Heckel, Jens-Ove; Rietschel, Wolfram; Hufert, Frank T.

    2000-01-01

    We characterized hepatitis B virus (HBV) isolates from sera of 21 hepatitis B virus surface antigen-positive apes, members of the families Pongidae and Hylobatidae (19 gibbon spp., 1 chimpanzee, and 1 gorilla). Sera originate from German, French, Thai, and Vietnamese primate-keeping institutions. To estimate the phylogenetic relationships, we sequenced two genomic regions, one located within the pre-S1/pre-S2 region and one including parts of the polymerase and the X protein open reading frames. By comparison with published human and ape HBV isolates, the sequences could be classified into six genomic groups. Four of these represented new genomic groups of gibbon HBV variants. The gorilla HBV isolate was distantly related to the chimpanzee isolate described previously. To confirm these findings, the complete HBV genome from representatives of each genomic group was sequenced. The HBV isolates from gibbons living in different regions of Thailand and Vietnam could be classified into four different phylogenetically distinct genomic groups. The same genomic groups were found in animals from European zoos. Therefore, the HBV infections of these apes might have been introduced into European primate-keeping facilities by direct import of already infected animals from different regions in Thailand. Taken together, our data suggest that HBV infections are indigenous in the different apes. One event involving transmission between human and nonhuman primates in the Old World of a common ancestor of human HBV genotypes A to E and the ape HBV variants might have occurred. PMID:10799618

  15. Molecular mechanisms of hepatic fibrosis in non-alcoholic steatohepatitis.

    PubMed

    Rombouts, Krista; Marra, Fabio

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in Western countries. The more severe form of this condition, non-alcoholic steatohepatitis (NASH), may progress to cirrhosis and its complications. Fibrosis and cirrhosis are the final outcomes of all chronic liver diseases; however, some morphological and biological differences distinguish fibrosis due to NASH from the forms secondary to other causes of liver damage. Fibrosis due to NASH develops primarily in the pericentral areas, surrounding groups of hepatocytes and thickening the space of Disse. This pericellular fibrosis eventually forms septa isolating regenerating nodules. The main cell type responsible for extracellular matrix deposition is represented by hepatic stellate cells that undergo activation in conditions of liver injury enabling them to participate in the liver wound healing process. Although the profibrogenic mechanisms operating in NASH are partly in common with those observed in other chronic liver diseases, the altered pattern of circulating adipokines, oxidative stress generation and the hormonal profile associated with the metabolic syndrome might have a specific role for the induction of fibrogenesis in this condition. In this paper, we review recent developments regarding the basic mechanisms of NASH and the involvement of hepatic stellate cells in this disease.

  16. Delta-like 1 homolog in Capra hircus: molecular characteristics, expression pattern and phylogeny.

    PubMed

    Hu, Jiangtao; Zhao, Wei; Zhan, Siyuan; Xiao, Ping; Zhou, Jingxuan; Wang, Linjie; Li, Li; Zhang, Hongping; Niu, Lili; Zhong, Tao

    2016-06-01

    To research the molecular characteristics, expression pattern and phylogeny of the Delta-like 1 homolog gene (Dlk1) in goats. Dlk1 transcripts were identified in the Jianyang Da'er goats by reverse-transcription polymerase chain reaction (RT-PCR). Phylogenetic trees were constructed by Bayesian inference and neighbor-joining methods. Quantitative real-time PCR (qPCR), western blotting and in situ hybridization were performed to analyze the expression pattern of Dlk1. Five alternatively transcripts were identified in different tissues and designated as Dlk1-AS1, 2, 3, 4 and 5. Compared with the normal transcript Dlk1-AS1, Dlk1-AS4 and Dlk1-AS5 retained the identical open reading frame (ORF) and encoded proteins with truncated epidermal-growth-factor like repeats of 121 and 83 amino acids, respectively. Using the Bayesian inference method, the consensus phylogenetic tree indicated that caprine Dlk1 had a closer relationship with bovine Dlk1 than with Dlk1 from pigs, humans and mice. qPCR revealed high expression levels of Dlk1 in the kidney (P < 0.01). However, mRNA and protein levels presented an inconsistent correlation, possibly because of post-transcriptional regulation. RNA in situ hybridization indicated that Dlk1 mRNA was localized in the interlobular bile duct and alongside the hepatocyte nuclei, in the epithelial cells of proximal and distal convoluted tubules and in the connective region between the mesothelium and myocardium in the heart. The Dlk1 gene in goats produces alternatively spliced transcripts, with specific expression and cellular localization patterns. These findings would lay the foundation for further study.

  17. Application of mass spectrometry to molecular surveillance of hepatitis B and C viral infections.

    PubMed

    Ganova-Raeva, Lilia M; Dimitrova, Zoya E; Campo, David S; Khudyakov, Yury

    2012-01-01

    Detection of genotypes and drug resistance mutations are important molecular tools assisting in clinical management of patients with chronic hepatitis B and C. Together with methods for assessment of genetic heterogeneity and relatedness of viral strains, they form the foundation of molecular surveillance. Currently, all these methods are based mainly on DNA sequencing followed by phylogenetic analysis. Mass spectrometry (MS) emerged recently as a rapid, cost-effective, reproducible and accurate alternative approach. MS-based molecular assays are highly amenable to automation and provide a suitable platform for routine application to the surveillance of HBV and HCV infections.

  18. Molecular characterization of hepatitis B virus X gene in chronic hepatitis B patients

    PubMed Central

    2012-01-01

    Background HBV-X protein is associated with the pathogenesis of HBV related diseases, specially in hepatocellular carcinomas of chronic patients. Genetic variability of the X gene includes genotypic specific variations and mutations emerging during chronic infection. Its coding sequence overlaps important regions for virus replication, including the basal core promoter. Differences in the X gene may have implications in biological functions of the protein and thus, affect the evolution of the disease. There are controversial results about the consequences of mutations in this region and their relationship with pathogenesis. The purpose of this work was to describe the diversity of HBV-X gene in chronic hepatitis patients infected with different genotypes, according to liver disease. Methods HBV-X gene was sequenced from chronic hepatitis B patient samples, analyzed by phylogeny and genotyped. Nucleotide and aminoacid diversity was determined calculating intragenetic distances. Mutations at 127, 130 and 131 aminoacids were considered in relation to liver disease. Results The most prevalent genotype detected in this cohort was F (F1 and F4), followed by D and A. Most of the samples corresponding to genotypes A and F1 were HBeAg(+) and for genotypes D and F4, HBeAg(−) samples were represented in a higher percentage. Intragenetic distance values were higher in HBeAg(−) than in positive samples for all genotypes, and lower in overlapped regions, compared to single codification ones. Nucleotide and aminoacid diversities were higher in HBeAg(−), than in HBeAg(+) samples. Conclusions Independently of the infecting genotypes, mutations at any of 127, 130 and/or 131 aminoacid positions and HBeAg(−) status were associated with mild liver disease in this cohort. PMID:22769058

  19. Characterization of Si volume- and delta-doped InGaAs grown by molecular beam epitaxy

    SciTech Connect

    Fedoryshyn, Y.; Kaspar, P.; Jaeckel, H.; Beck, M.

    2010-05-15

    Bulk InGaAs layers were grown at 400 deg. C lattice-matched to InP semi-insulating substrates by molecular beam epitaxy. Si doping of the layers was performed by applying volume- and delta-doping techniques. The samples were characterized by capacitance-voltage, van der Pauw-Hall, secondary ion mass spectroscopy and photoluminescence measurements. Good agreement in terms of dependence of mobility and Burstein-Moss shift shift on doping concentration in samples doped by the two different techniques was obtained. Amphoteric behavior of Si was observed at doping concentrations higher than {approx}2.9x10{sup 19} cm{sup -3} in both delta- and volume-doped samples. Degradation of InGaAs crystalline quality occurred in samples with Si concentrations higher than {approx}4x10{sup 19} cm{sup -3}.

  20. Paleo-Reconstruction of Carbon Cycling in Large-River Delta-Front Estuaries: Use of Molecular Biomarkers

    NASA Astrophysics Data System (ADS)

    Bianchi, T. S.

    2014-12-01

    The burial of organic carbon (OC) in river deltas and continental margins worldwide account for approximately 90% of the carbon burial in the ocean. In particular, sediments in large-river delta-front estuaries have been shown to be repositories and integrators of land-use change across expansive watersheds that drain the continents to the ocean. Thus, separating natural and human-driven changes in the transport of terrestrial organic carbon (TOC) to ocean is important in understanding the effects of climate change on TOC fluxes. Molecular biomarkers of TOC (e.g., lignin phenols, fatty acids, sterols) in LDE sediments have been used extensively to reconstruct of carbon cycling changes that are reflective of land-use change in the watersheds. However, due to the highly variable hydrologic regimes across continents, continental margins (e.g., active versus passive), and coastal dynamics in LDEs, the fate and transport of these molecular biomarkers varies considerably. Here I will discuss some of the key molecular biomarkers that have been used to date in such historical reconstruction exercises in LDEs (e.g., Mississippi/Atchafalaya, Yangtze, Yellow, Ganges-Brahmaputra, Colville Rivers), and explore how margin-type, residence time of transport, redox, and molecular stability, to name a few, impact the utility of using different biomarkers in paleo-reconstruction studies.

  1. TRIB1 downregulates hepatic lipogenesis and glycogenesis via multiple molecular interactions.

    PubMed

    Ishizuka, Yuumi; Nakayama, Kazuhiro; Ogawa, Ayumi; Makishima, Saho; Boonvisut, Supichaya; Hirao, Atsushi; Iwasaki, Yusaku; Yada, Toshihiko; Yanagisawa, Yoshiko; Miyashita, Hiroshi; Takahashi, Masafumi; Iwamoto, Sadahiko

    2014-04-01

    Mammalian tribbles homolog 1 (TRIB1) regulates hepatic lipogenesis and is genetically associated with plasma triglyceride (TG) levels and cholesterol, but the molecular mechanisms remain obscure. We explored these mechanisms in mouse livers transfected with a TRIB1 overexpression, a shRNA template or a control (LacZ) adenovirus vector. The overexpression of TRIB1 reduced, whereas induction of the shRNA template increased, plasma glucose, TG, and cholesterol and simultaneously hepatic TG and glycogen levels. The involvement of TRIB1 in hepatic lipid accumulation was supported by the findings of a human SNP association study. A TRIB1 SNP, rs6982502, was identified in an enhancer sequence, modulated enhancer activity in reporter gene assays, and was significantly (P=9.39 × 10(-7)) associated with ultrasonographically diagnosed non-alcoholic fatty liver disease in a population of 5570 individuals. Transcriptome analyses of mouse livers revealed significant modulation of the gene sets involved in glycogenolysis and lipogenesis. Enforced TRIB1 expression abolished CCAAT/enhancer binding protein A (CEBPA), CEBPB, and MLXIPL proteins, whereas knockdown increased the protein level. Levels of TRIB1 expression simultaneously affected MKK4 (MAP2K4), MEK1 (MAP2K1), and ERK1/2 (MAPK1/3) protein levels and the phosphorylation of JNK, but not of ERK1/2. Pull-down and mammalian two-hybrid analyses revealed novel molecular interaction between TRIB1 and a hepatic lipogenic master regulator, MLXIPL. Co-expression of TRIB1 and CEBPA or MLXIPL reduced their protein levels and proteasome inhibitors attenuated the reduction. These data suggested that the modulation of TRIB1 expression affects hepatic lipogenesis and glycogenesis through multiple molecular interactions.

  2. Molecular analysis of hepatitis A virus strains obtained from patients with acute hepatitis A in Mongolia, 2004-2013.

    PubMed

    Tsatsralt-Od, Bira; Baasanjav, Nachin; Nyamkhuu, Dulmaa; Ohnishi, Hiroshi; Takahashi, Masaharu; Kobayashi, Tominari; Nagashima, Shigeo; Nishizawa, Tsutomu; Okamoto, Hiroaki

    2016-04-01

    Despite the high endemicity of hepatitis A virus (HAV) in Mongolia, the genetic information on those HAV strains is limited. Serum samples obtained from 935 patients with acute hepatitis in Ulaanbaatar, Mongolia during 2004-2013 were tested for the presence of HAV RNA using reverse transcription-PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 180 patients (19.3%) had detectable HAV RNA. These 180 isolates shared 94.6-100% identity and formed four phylogenetic clusters within subgenotype IA. One or three representative HAV isolates from each cluster exhibited 2.6-3.9% difference between clusters over the entire genome. Cluster 1 accounted for 65.0% of the total, followed by Cluster 2 (30.6%), Cluster 3 (3.3%), and Cluster 4 (1.1%). Clusters 1 and 2 were predominant throughout the observation period, whereas Cluster 3 was undetectable in 2009 and 2013 and Cluster 4 became undetectable after 2009. The Mongolian HAV isolates were closest to those of Chinese or Japanese origin (97.7-98.5% identities over the entire genome), suggesting the evolution from a common ancestor with those circulating in China and Japan. Further molecular epidemiological analyses of HAV infection are necessary to investigate the factors underlying the spread of HAV and to implement appropriate prevention measures in Mongolia.

  3. Molecular tracing of Japan-indigenous hepatitis E viruses.

    PubMed

    Tanaka, Yasuhito; Takahashi, Kazuaki; Orito, Etsuro; Karino, Yoshiyasu; Kang, Jong-Hon; Suzuki, Kazuyuki; Matsui, Atsushi; Hori, Akiko; Matsuda, Hiroyuki; Sakugawa, Hiroshi; Asahina, Yasuhiro; Kitamura, Tsuneo; Mizokami, Masashi; Mishiro, Shunji

    2006-04-01

    The ancestor(s) of apparently Japan-indigenous strains of Hepatitis E virus (HEV) was probably of foreign origin, but it remains unclear when and from where it made inroads. In this study, 24 genotype 3 and 24 genotype 4 HEV strains recovered in Japan each showed a significant cluster, clearly distinct from those of foreign strains, in the phylogenetic tree constructed from an 821 nt RNA polymerase gene fragment. The evolutionary rate, approximately 0.8 x 10(-3) nucleotide substitutions per site per year, enabled tracing of the demographic history of HEV and suggested that the ancestors of Japan-indigenous HEV had made inroads around 1900, when several kinds of Yorkshire pig were imported from the UK to Japan. Interestingly, the evolutionary growth of genotype 3 in Japan has been slow since the 1920s, whereas genotype 4 has spread rapidly since the 1980s. In conclusion, these data suggest that the indigenization and spread of HEV in Japan were associated with the popularization of eating pork.

  4. Molecular diagnosis and treatment of drug-resistant hepatitis B virus.

    PubMed

    Kim, Jeong Han; Park, Yong Kwang; Park, Eun-Sook; Kim, Kyun-Hwan

    2014-05-21

    Oral antiviral agents have been developed in the last two decades for the treatment of chronic hepatitis B (CHB). However, antiviral resistance remains an important challenge for long-term CHB therapy. All of the clinically available oral antiviral agents are nucleoside or nucleotide analogues that target the activity of viral reverse transcriptase (RT), and all are reported to have resistant mutations. Since the hepatitis B virus (HBV) RT, like other viral polymerases, lacks proofreading activity, the emergence of drug-resistance occurs readily under selective pressure from the administration of antiviral agents. The molecular diagnosis of drug-resistant HBV is based on sequence variations, and current diagnostic methods include sequencing, restriction fragment polymorphism analysis, and hybridization. Here, we will discuss the currently available molecular diagnosis tools, in vitro phenotypic assays for validation of drug-resistant HBV, and treatment options for drug-resistant HBV.

  5. [Molecular characteristic of duck hepatitis A virus type 1 causing pancreatitis ].

    PubMed

    Fu, Guanghua; Huang, Yu; Fu, Qiuling; Cheng, Longfei; Wan, Chunhe; Shi, Shaohua; Chen, Hongmei; Lin, Jiansheng; Lin, Fang

    2014-09-04

    [OBJECTIVE] We studied the molecular characteristics of the full-length genome of duck hepatitis A virus type 1 causing pancreatitis in Muscovy ducklings. [METHODS] We determined the entire genomic sequence of duck hepatitis A virus type 1 strain MPZJ1206 using reverse transcription polymerase chain reaction assay and analyzed the bioinformatics of the viral genome sequence. [ RESULTS] The genome length of strain MPZJ1206 comprised 7703 bases, with a G + C content of 43.05%. The genome of MPZJ1206 contains a single, long open reading frame encoding a polypeptide of 2249 amino acids, with a genomic orgariization similar to those of other isolates of duck hepatitis A virus type 1. MPZJ1206 is identical with previously isolates by 93. 5% - 99. 6% in nucleotide sequence and 97. 9% - 99. 6% in amino acid sequence and shares genetic distance no more than 7%. Phylogenetic analysis based on genome sequence indicates that MPZJ1206 shares a close genetic relationship with two strains isolated in 2011. [CONCLUSION] Although pathotype caused by MPZJ1206 strain is significantly distinct from those induced by classical isolates of duck hepatitis A virus type 1, the genome of MPZJ1206 shares high homology with those of previous isolates. The change of pathotype may result from an alteration in viral tissue tropism of MPZJ1206.

  6. Two years' experience of implementing molecular screening of hepatitis B virus, hepatitis C virus and human immunodeficiency virus 1, 2 in Riyadh blood donors.

    PubMed

    Mohamud, Hanat S; Mohamed, Deqa H; Alqahtani, Farjah H; Almajid, Fahad M; Alswat, Khalid; Somily, Ali M

    2016-04-01

    Molecular screening technologies have improved blood safety by reducing the number of window-period transmissions relative to serological screening. In the two years following the introduction of molecular testing in King Khalid University Hospital, Saudi Arabia, 25,920 donor samples were screened in parallel by both serological and molecular techniques for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). No HCV or HIV NAT yields were detected. However, molecular screening enabled the interdiction of two confirmed HBV NAT yields. This is only the second report of confirmed HBV NAT yield in the Kingdom of Saudi Arabia, and amongst the few reports in the wider Middle East and North Africa region.

  7. Hepatic nuclear receptor PPARalpha in the koala (Phascolarctos cinereus): cloning and molecular characterisation.

    PubMed

    Ngo, Suong Ngoc Thi; McKinnon, Ross Allan; Stupans, Ieva

    2007-09-01

    Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear/steroid receptor gene superfamily that plays an essential role in fatty acid metabolism. PPARalpha modulates the expression of genes encoding peroxisomal fatty acid beta-oxidation enzymes and microsomal fatty acid hydroxylases CYP4As. We have previously reported that the obligate Eucalyptus feeder koala (Phascolarctos cinereus) exhibits a higher hepatic CYP4A activity and an absence of peroxisomal palmitoyl-CoA oxidation as compared to non-Eucalyptus feeders human, rat or wallaby. Here we describe the cloning, expression and molecular characterisation of koala hepatic PPARalpha. A full-length PPARalpha cDNA of size 1515 bp was cloned by reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The koala PPARalpha cDNA encodes a protein of 468 amino acids. Transfection of the koala PPARalpha cDNA into Cos-7 cells resulted in the expression of a protein recognised by a rabbit anti-human PPARalpha polyclonal antibody. PPARalpha immunoreactive bands of the same molecular mass were detected in nuclear extracts of koala livers. The results of this study demonstrate the presence of koala hepatic PPARalpha which shares several common features with other published PPARalphas; however, it exhibits important differences in both the DNA and ligand binding domains.

  8. The gene controlling marijuana psychoactivity: molecular cloning and heterologous expression of Delta1-tetrahydrocannabinolic acid synthase from Cannabis sativa L.

    PubMed

    Sirikantaramas, Supaart; Morimoto, Satoshi; Shoyama, Yoshinari; Ishikawa, Yu; Wada, Yoshiko; Shoyama, Yukihiro; Taura, Futoshi

    2004-09-17

    Delta(1)-tetrahydrocannabinolic acid (THCA) synthase is the enzyme that catalyzes oxidative cyclization of cannabigerolic acid into THCA, the precursor of Delta(1)-tetrahydrocannabinol. We cloned a novel cDNA (GenBank trade mark accession number AB057805) encoding THCA synthase by reverse transcription and polymerase chain reactions from rapidly expanding leaves of Cannabis sativa. This gene consists of a 1635-nucleotide open reading frame, encoding a 545-amino acid polypeptide of which the first 28 amino acid residues constitute the signal peptide. The predicted molecular weight of the 517-amino acid mature polypeptide is 58,597 Da. Interestingly, the deduced amino acid sequence exhibited high homology to berberine bridge enzyme from Eschscholtzia californica, which is involved in alkaloid biosynthesis. The liquid culture of transgenic tobacco hairy roots harboring the cDNA produced THCA upon feeding of cannabigerolic acid, demonstrating unequivocally that this gene encodes an active THCA synthase. Overexpression of the recombinant THCA synthase was achieved using a baculovirus-insect expression system. The purified recombinant enzyme contained covalently attached FAD cofactor at a molar ratio of FAD to protein of 1:1. The mutant enzyme constructed by changing His-114 of the wild-type enzyme to Ala-114 exhibited neither absorption characteristics of flavoproteins nor THCA synthase activity. Thus, we concluded that the FAD binding residue is His-114 and that the THCA synthase reaction is FAD-dependent. This is the first report on molecular characterization of an enzyme specific to cannabinoid biosynthesis.

  9. Identification of a natural intergenotypic recombinant hepatitis delta virus genotype 1 and 2 in Vietnamese HBsAg-positive patients.

    PubMed

    Sy, B T; Nguyen, H M; Toan, N L; Song, L H; Tong, H V; Wolboldt, C; Binh, V Q; Kremsner, P G; Velavan, T P; Bock, C-T

    2015-01-01

    Hepatitis D virus (HDV) infection is acquired as a co- /superinfection of Hepatitis B virus (HBV) and can modulate the pathophysiology of chronic hepatitis B and related liver diseases including hepatocellular carcinoma. Among the eight distinct HDV genotypes reported, relatively few studies have attempted to investigate the prevalence of HDV mixed genotypes and RNA recombination of HDV. With a recorded prevalence of 10-20% HBV infection in Vietnam, this study investigated the HDV variability, HDV genotypes and HDV recombination among twenty-one HDV isolates in Vietnamese HBsAg-positive patients. HDV subgenomic and full-length genome sequences were obtained using newly established HDV-specific RT-PCR techniques. The nucleotide homology was observed from 74.6% to 99.4% among the investigated full-length genome of the HDV isolates. We observed HDV genotype 1 and HDV genotype 2 in the investigated Vietnamese patients. Although no HDV genotype mixtures were observed, we report here a newly identified recombinant of HDV genotypes (HDV 1 and HDV 2). The identified recombinant HDV isolate C03 revealed sequence homology to both HDV genotype 1 (nt1 to nt907) and HDV genotype 2 (nt908 to nt1675; HDAg coding region) with a breakpoint at nt908. Our findings demonstrate the prevalence of intergenotypic recombination between HDV genotypes 1 and 2 in a Vietnamese HBsAg-positive patient. Extended investigation on the distribution and prevalence of HDV, HDV mixed genotypes and recombinant HDV genotypes in a larger Vietnamese population offers vital insights into understanding of the micro-epidemiology of HDV and subsequent pathophysiology in chronic HBV- /HDV-related liver diseases.

  10. The Delta 32 mutation of the chemokine-receptor 5 gene neither is correlated with chronic hepatitis C nor does it predict response to therapy with interferon-alpha and ribavirin.

    PubMed

    Glas, J; Török, H P; Simperl, C; König, A; Martin, K; Schmidt, F; Schaefer, M; Schiemann, U; Folwaczny, C

    2003-07-01

    Unlike in HIV, homozygosity for a 32-bp deletion (Delta 32) of the chemokine receptor 5 (CCR5) gene was recently described in increased frequency in patients with chronic hepatitis C (HCV). Thus, it was speculated that this mutation might be relevant for disease susceptibility and influence the response to antiviral therapy. The present study sought to confirm the association between HCV and the Delta 32 mutation of the CCR5 gene and to correlate it with the response to therapy with interferon-alpha-2a and ribavirin. Sixty-two patients with HCV and 119 healthy unrelated controls were genotyped for the Delta 32 mutation. For the correlation between the Delta 32 mutation and response to therapy, only patients (n = 59) who completed 6 months of combination therapy as part of a prospective study were evaluated. The Delta 32 mutation was not observed in increased frequency in HCV. Furthermore, a significant difference of the HCV load or aminotransferase concentrations was not observed in carriers versus noncarriers of the Delta 32 mutation. After stratification for potentially confounding factors such as gender or HCV genotype, a significant difference was also not detected with respect to treatment outcome. These observations argue strongly against a role of CCR5 for susceptibility to HCV infection or response to combination therapy.

  11. Prevalence and predictors for compensated Advanced Chronic Liver Disease (c-ACLD) in patients with chronic Hepatitis Delta Virus (HDV) infection

    PubMed Central

    Couto, Ingrid; Victoria, Marilu; Veloso, Valdiléa G.; Rodrigues, Lorena; Grinsztejn, Beatriz; Lacerda, Marcus; Victoria, Flamir; Perazzo, Hugo

    2017-01-01

    Objective The study aimed to evaluate the prevalence and predictor factors for compensated advanced chronic liver disease (c-ACLD) in patients with hepatitis Delta virus (HDV) infection. Methods This cross-sectional study included consecutive HDV-infected patients defined by positive anti-HDV. Patients with hepatitis C coinfection, liver transplantation or presence of conditions that limit liver (LSM) or spleen stiffness measurement (SSM) were excluded. Blood tests, abdominal ultrasound, SSM and LSM by transient elastography (FibroScan®) were performed at the same day. Alcohol consumption was quantified using the AUDIT score and c-ACLD was defined by LSM ≥ 15 kPa performed by an experimented operator blinded for clinical and laboratory data. Results 101 patients were eligible and few patients were excluded due to negative anti-HDV (n = 7), hepatitis C coinfection (n = 2), liver transplantation (n = 10) and limitation for LSM or SSM (n = 5). Therefore, 77 patients [61% male, age = 43 (IQR,36–52) years] were included. The prevalence of c-ACLD was 57% (n = 44/77). Patients with c-ACLD had a higher rate of detectable HBV viral load (p = 0.039), higher levels of transaminases, GGT, alkaline phosphatases, total bilirubin and INR (p<0.001 for all), as well as lower platelet count and albumin levels (p>0.001 for both) compared to those without c-ACLD. Patients with c-ACLD had higher SSM [65.2 (IQR,33.8–75.0) vs 21.8 (16.5–32.0) kPa; p<0.001] and higher splenic volume [475 (IQR,311–746) vs 154 (112–283) cm3; p<0.001] compared to those without. Detectable HBV viral load (>10 UI/ml), alkaline phosphatase (per IU/L) and GGT levels (per IU/L) were independently associated with c-ACLD in all multivariate models. Splenic volume [per cm3,OR = 1.01 (95%CI,1.01–1.02);p = 0.002], SSM [per kPa, OR = 1.04 (1.01–1.07);p = 0.012] and splenomegaly [yes vs no,OR = 28.45 (4.42–182.95);p<0.001] were independently associated with c-ACLD. Conclusions The prevalence of c

  12. Processing and Translation Initiation of Non-long Terminal Repeat Retrotransposons by Hepatitis Delta Virus (HDV)-like Self-cleaving Ribozymes*

    PubMed Central

    Ruminski, Dana J.; Webb, Chiu-Ho T.; Riccitelli, Nathan J.; Lupták, Andrej

    2011-01-01

    Many non-long terminal repeat (non-LTR) retrotransposons lack internal promoters and are co-transcribed with their host genes. These transcripts need to be liberated before inserting into new loci. Using structure-based bioinformatics, we show that several classes of retrotransposons in phyla-spanning arthropods, nematodes, and chordates utilize self-cleaving ribozymes of the hepatitis delta virus (HDV) family for processing their 5′ termini. Ribozyme-terminated retrotransposons include rDNA-specific R2, R4, and R6, telomere-specific SART, and Baggins and RTE. The self-scission of the R2 ribozyme is strongly modulated by the insertion site sequence in the rDNA, with the most common insertion sequences promoting faster processing. The ribozymes also promote translation initiation of downstream open reading frames in vitro and in vivo. In some organisms HDV-like and hammerhead ribozymes appear to be dedicated to processing long and short interspersed elements, respectively. HDV-like ribozymes serve several distinct functions in non-LTR retrotransposition, including 5′ processing, translation initiation, and potentially trans-templating. PMID:21994949

  13. Unraveling the complexity of hepatitis B virus: from molecular understanding to therapeutic strategy in 50 years.

    PubMed

    Liu, Bo; Wen, Xin; Huang, Canhua; Wei, Yuquan

    2013-09-01

    Hepatitis B virus (HBV) is a well-known hepadnavirus with a double-stranded circular DNA genome. Although HBV was first described approximately 50 years ago, the precise mechanisms of HBV infection and effective therapeutic strategies remain unclear. Here, we focus on summarizing the complicated mechanisms of HBV replication and infection, as well as genomic factors and epigenetic regulation. Additionally, we discuss in vivo models of HBV, as well as diagnosis, prevention and therapeutic drugs for HBV. Together, the data in this 50-year review may provide new clues to elucidate molecular mechanisms of HBV pathogenesis and shed new light on the future HBV therapies.

  14. Morphologic and molecular identifications of digenetic trematodes in double-crested cormorants (Phalacrocorax auritus) from the Mississippi Delta, USA.

    PubMed

    O'Hear, Mary; Pote, Linda; Yost, Marlena; Doffitt, Cynthia; King, Tommy; Panuska, Carla

    2014-01-01

    Increasing numbers of Double-crested Cormorants (Phalacrocorax auritus) in the Mississippi River Delta, USA, have been observed over the past few decades. This piscivorous bird is a definitive host for numerous digenetic trematodes, some of which may cause pathology in a fish host. We conducted a 2-yr survey of intestinal trematodes in 35 Double-crested Cormorants collected in the Mississippi Delta. We counted gastrointestinal trematodes, identified them to species using morphometric and molecular techniques, and sequenced the 18S and cytochrome oxidase I (COI) genes. We collected 4,909 trematodes, representing five digenetic species: Drepanocephalus spathans, Hysteromorpha triloba, Pseudopsilostoma varium, Austrodiplostomum ostrowskiae, and Ascocotyle longa. The most prevalent trematode of the Double-crested Cormorants was D. spathans (91%), followed by H. triloba (78%), P. varium (74%), A. ostrowskiae (57%), and A. longa (29%). Among these, the life cycles are only known for H. triloba and A. longa. Novel DNA sequences of the COI gene were obtained for D. spathans, A. ostrowskiae, P. varium, and A. longa adults. Using these DNA sequences, the identification and confirmation of the larval stages of these parasites in the fish and snail hosts will be possible.

  15. Serological Patterns and Molecular Characterization of Occult Hepatitis B Virus Infection among Blood Donors

    PubMed Central

    Lin, Hong; Zhao, Hong; Tang, Xinyi; Hu, Wenjia; Jiang, Nizheng; Zhu, Shaowen; Huang, Chengyin

    2016-01-01

    Background Hepatitis B infections, characterized by the presence of a viral genome without detectable hepatitis B surface antigen (HBsAg; Occult hepatitis B infection [OBI]), have been reported recently. Objectives We performed serological and molecular characterization of OBI among blood donors at Jiangsu province blood center during years 2013 and 2014. Methods All donor samples were routinely screened by double enzyme-linked immunosorbent assay (ELISA) for hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), Treponema pallidum (TP), and alanine aminotransferase (ALT). Single-reactive, nonreactive, and ALT-elevated samples were pooled or resolved by nucleic acid testing (NAT). Seromarkers were examined in HBsAg-/DNA+ samples. After 1 to 12 months of follow up, seromarkers were screened again to verify OBI samples. Results We studied 157119 samples from blood donors. A total of 154397 ELISA nonreactive donor samples were identified, and HBV DNA was detected in 81 samples; no samples were positive for HIV or HCV RNA. Hepatitis B virus viral loads in most donors were less than 20 - 200 IU/mL. There was only one HBsAg-positive sample. Eighty HBsAg-/DNA+ samples were evaluated further. Of these samples, 85% (68/80) were reactive for anti-HBc and 36.2% (29/800) were reactive for anti-HBc and anti-HBs; 11.3% (9/80) did not have any detectable serological markers. Twenty-nine donors were followed up. One was HBsAg ELISA positive, and of six seronegative donors, all had anti-HBc and anti-HBs, but were negative for DNA. Samples were HBV genotypes B, C and D. Mutations in the S region of HBV DNA included S114T, G119R, P120S, T125M, C139Y, T140I, C147W, T148A, A159V/G, E164D, V168A, and R169C. Conclusions Overall, we found that OBI was rare, but that the prevalence of OBI was slightly higher in Jiangsu than in other areas of China. PMID:27882070

  16. Preliminary molecular epidemiological investigation of hepatitis E virus sequences from Québec, Canada.

    PubMed

    Wilhelm, Barbara; Muellner, Petra; Pearl, David L; Rajić, Andrijana; Houde, Alain; McEwen, Scott A

    2015-03-01

    Our study objective was to describe the Canadian Hepatitis E virus (HEV) sequences currently cataloged in GenBank from three populations: commercially raised pigs, retail pork, and locally acquired Hepatitis E cases, and to interpret the molecular evidence they provide. We searched the GenBank for any/all Canadian HEV sequences from these populations, and identified highly similar matches using the Basic Local Alignment Search Tool (BLAST) algorithm, studying sequences of the partial ORF2 gene. We validated the findings made using Multiple Sequence Comparison by Log-Expectation (MUSCLE) and Clustal 2 programs for multiple sequence alignments, as inputs to estimate dendrograms using both neighbour-joining and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) methods. The GenBank search yielded 47 sequences collected from pigs: 32 sequences from two to four month old commercial pigs in Québec, one from three to four month old pigs at a research station in Ontario, one from two month old pigs in a commercial Saskatchewan herd, and 13 collected from finisher pigs in a national survey. Additionally, 14 sequences were collected from a national survey of Canadian retail pork livers, and seven sequences from two Canadian pediatric patients with locally acquired Hepatitis E, both from the province of Québec. All sequences belonged to genotype 3. Eight of the 14 sequences from retail pork livers had human-derived sequences in their top ten BLAST matches; six did not. Those eight sequences having close human BLAST matches clustered within a dendrogram, as did those with no close human BLAST matches. Human sequences with close matches to the eight retail sequences included both of the Québec Hepatitis E cases, as well as sequences from Japanese Hepatitis E cases, and Japanese blood donors. Seven of the eight HEV sequences from retail liver with close human BLAST matches originated in Québec. Kulldorff's spatial scan statistic showed a significant (P<0.05) spatial

  17. Subpicomolar sensing of delta-opioid receptor ligands by molecular-imprinted polymers using plasmon-waveguide resonance spectroscopy.

    PubMed

    Devanathan, Savitha; Salamon, Zdzislaw; Nagar, Anoop; Narang, Subhash; Schleich, Donald; Darman, Paul; Hruby, Victor; Tollin, Gordon

    2005-04-15

    Here we report, for the first time, the formation of a biomimetic covalently imprinted polymeric sensor for a target ligand, the delta-opioid G-protein coupled receptor agonist DPDPE, which reproducibly exhibits subpicomolar binding affinity in an aqueous environment. In addition to having a well-defined and homogeneous binding site, the imprinted polymer template is quite stable to storage in both the dry and wet states and has at least 6 orders of magnitude higher affinities than exhibited by similar peptide-based molecular-imprinted polymers (MIPs) thus far. A highly sensitive optical detection methodology, plasmon-waveguide resonance spectroscopy, was employed, capable of measuring binding in real time and discriminating between ligand molecules, without requiring labeling protocols (fluorophores or radioisotopes). The DPDPE-imprinted polymer showed a broad structure-activity relationship profile, not unlike that found for protein receptors. Such sensitivity and robustness of MIPs suggests potential applications ranging from biowarfare agent detection to pharmaceutical screening.

  18. Molecular and morphological characterization of myxozoan actinospore types from a commercial catfish pond in the Mississippi delta.

    PubMed

    Rosser, Thomas G; Griffin, Matt J; Quiniou, Sylvie M A; Greenway, Terrence E; Khoo, Lester H; Wise, David J; Pote, Linda M

    2014-12-01

    The actinospore diversity of infected Dero digitata was surveyed (May 2011) from a channel catfish (Ictalurus punctatus) production pond in the Mississippi Delta region for the elucidation of unknown myxozoan life cycles. At present, only 2 myxozoan life cycles have been molecularly confirmed in channel catfish, linking the actinospore stage from an aquatic oligochaete (D. digitata ) and the myxospore stage from the catfish. In this study D. digitata (n = 2,592) were isolated from oligochaetes collected from the bottom sediment of a channel catfish production pond. After 1 wk of daily observation, a total of 6 genetically different actinospore types were observed. The collective groups were classified as 2 aurantiactinomyxons, 2 helioactinomyxons, 1 raabeia, and 1 triactinomyxon. Overall prevalence of myxozoan infections in the isolated oligochaetes was 4.4%. Actinospores were photographed and measured for morphological characterization. Four previously undescribed actinospore types were identified and characterized molecularly and morphologically. Phylogenetic analysis revealed the raabeia and one of the helioactinomyxon (type 1) actinospores were closely related to the group of myxozoans known to parasitize ictalurids in North America. To date, no myxospores have been linked to the newly sequenced actinospores reported in this survey. The morphological and molecular data generated from this study will assist in the identification of myxospore counterparts for these actinospore stages and aid in the elucidation of unknown myxozoan life cycles in closed production systems.

  19. Molecular sequence data of hepatitis B virus and genetic diversity after vaccination.

    PubMed

    van Ballegooijen, W Marijn; van Houdt, Robin; Bruisten, Sylvia M; Boot, Hein J; Coutinho, Roel A; Wallinga, Jacco

    2009-12-15

    The effect of vaccination programs on transmission of infectious disease is usually assessed by monitoring programs that rely on notifications of symptomatic illness. For monitoring of infectious diseases with a high proportion of asymptomatic cases or a low reporting rate, molecular sequence data combined with modern coalescent-based techniques offer a complementary tool to assess transmission. Here, the authors investigate the added value of using viral sequence data to monitor a vaccination program that was started in 1998 and was targeted against hepatitis B virus in men who have sex with men in Amsterdam, the Netherlands. The incidence in this target group, as estimated from the notifications of acute infections with hepatitis B virus, was low; therefore, there was insufficient power to show a significant change in incidence. In contrast, the genetic diversity, as estimated from the viral sequence collected from the target group, revealed a marked decrease after vaccination was introduced. Taken together, the findings suggest that introduction of vaccination coincided with a change in the target group toward behavior with a higher risk of infection. The authors argue that molecular sequence data provide a powerful additional monitoring instrument, next to conventional case registration, for assessing the impact of vaccination.

  20. Molecular evolution in court: analysis of a large hepatitis C virus outbreak from an evolving source

    PubMed Central

    2013-01-01

    Background Molecular phylogenetic analyses are used increasingly in the epidemiological investigation of outbreaks and transmission cases involving rapidly evolving RNA viruses. Here, we present the results of such an analysis that contributed to the conviction of an anesthetist as being responsible for the infection of 275 of his patients with hepatitis C virus. Results We obtained sequences of the NS5B and E1-E2 regions in the viral genome for 322 patients suspected to have been infected by the doctor, and for 44 local, unrelated controls. The analysis of 4,184 cloned sequences of the E1-E2 region allowed us to exclude 47 patients from the outbreak. A subset of patients had known dates of infection. We used these data to calibrate a relaxed molecular clock and to determine a rough estimate of the time of infection for each patient. A similar analysis led to an estimate for the time of infection of the source. The date turned out to be 10 years before the detection of the outbreak. The number of patients infected was small at first, but it increased substantially in the months before the detection of the outbreak. Conclusions We have developed a procedure to integrate molecular phylogenetic reconstructions of rapidly evolving viral populations into a forensic setting adequate for molecular epidemiological analysis of outbreaks and transmission events. We applied this procedure to a large outbreak of hepatitis C virus caused by a single source and the results obtained played a key role in the trial that led to the conviction of the suspected source. PMID:23870105

  1. DEVELOPMENT OF A MOLECULAR METHOD TO IDENTIFY THE MERGING PATHOGEN HEPATITIS E IN WATER SAMPLES

    EPA Science Inventory

    Hepatitis E virus (HEV) is an emerging pathogen that causes significant illness in the developing world. Like the hepatitis A virus, it is transmitted via the fecal-oral route and can cause short-term, acute hepatitis. In addition, hepatitis E has been found to cause a signific...

  2. DEVELOPMENT OF A MOLECULAR METHOD TO IDENTIFY THE EMERGING PATHOGEN HEPATITIS E IN WATER SAMPLES

    EPA Science Inventory

    Hepatitis E virus (HEV) is an emerging pathogen that causes significant illness in the developing world. Like the hepatitis A virus, it is transmitted via the fecal-oral route and can cause short-term, acute hepatitis. In addition, hepatitis E has been found to cause a signific...

  3. Molecular detection and typing of duck hepatitis A virus directly from clinical specimens.

    PubMed

    Fu, Yu; Pan, Meng; Wang, Xiaoyan; Xu, Yongliang; Yang, Hanchun; Zhang, Dabing

    2008-10-15

    To develop a new approach for the detection and typing of duck hepatitis A virus (DHAV), a pair of non-degenerate primers was designed to amplify a approximately 250-bp genomic region in the 5'UTR. 3 reference strains and 6 duck embryo-derived isolates from various regions in China, involving 2 serotypes, were successfully amplified with the primer set. By determining the nucleotide sequence of the amplicon, a molecular typing method was developed. If isolate sequences were compared to DHAV 5'UTR sequences available in public databases, nucleotide identity was > or =94% with homologous serotype and < or =73% with heterologous serotypes. Phylogenetic analysis revealed monophyletic clustering of 5'UTR sequences of a homologous serotype, confirming the new classification of DHAV (serotype 1 and the two new serotypes recently described in Taiwan and South Korea, respectively) into three genotypes (A, B and C) defined by the capsid coding region. Analysis of the results showed that the primer pair should aid in the detection of DHAV, and that the amplicon sequence contains type-specific information and can be used for effective and rapid molecular typing. The molecular methods proved their utility through the detection and typing of DHAV directly from 28 liver specimens collected from dead ducklings during duck viral hepatitis outbreaks in different regions of China between 2001 and 2007. The results confirmed the presence of DHAV in all of the 28 samples and demonstrated that genotypes A (13/28) and C (15/28) of DHAV are co-circulating in China.

  4. V{delta}1 T cell receptor binds specifically to MHC I chain related A: Molecular and biochemical evidences

    SciTech Connect

    Zhao Jianqing; Huang Jie; Chen Hui; Cui Lianxian; He Wei . E-mail: heweiimu@public.bta.net.cn

    2006-01-06

    Human MHC class I chain-related A (MICA) is a tumor-associated antigen that can be recognized by V{delta}1 subset of tumor-infiltrating {gamma}{delta} T cells. We previously reported that immobilized recombinant MICA protein could induce the proliferation of tumor-infiltrating V{delta}1 {gamma}{delta} T cells in vitro. But there has been no direct evidence showing the engagement of {gamma}{delta} T cell receptors (TCR) of the induced cells with MICA. In the current investigation, we show that MICA induces specific cytolytic activity of the expanded {gamma}{delta} T cells. We expressed the coupled V domains from the MICA-induced T cells as a single polypeptide chain V{delta}V{gamma} TCR ({gamma}{delta} scTCR). Such scTCR can specifically bind MICA of HeLa cells. Direct interaction of {gamma}{delta} scTCRs with in vitro expressed MICA was monitored using an IAsys biosensor. We found that the V{delta}1 scTCR can specifically bind to immobilized MICA molecule and MICA{alpha}1{alpha}2 domains are responsible for the binding reaction.

  5. Molecular epidemiology of hepatitis A virus in patients in the Ahwaz region of Iran.

    PubMed

    Nejati, Ahmad; Makvandi, Manochehr; Samarbafzadeh, Alireza; Neisi, Niloofar; Moradzadegan, Hamid

    2012-04-01

    Hepatitis A virus (HAV) is one of the etiologic agents of acute viral hepatitis, an important public health problem worldwide. The aim of this study was to investigate the genetic diversity of HAV in Southwest Iran (Ahwaz). A total of 59 sera were collected from acutely ill patients with anti-HAV IgM antibodies during 2009 and 2010 were tested also by RT-PCR targeting the 5' NCR for molecular diagnosis and examined in the VP1-2A and VP3-VP1 regions for genotyping. Twelve (20%) patients were detected VP1-2A by RT-PCR and 10 patients had VP3-VP1. The resulting amplicons were sequenced for genotype identification. All HAV strains were identified as subgenotype IB. Phylogenetic analysis revealed an extensive genetic heterogeneity among the strains. Seven hundred sixty-five S→F and 788 K→R amino acid substitutions in IRI49 isolate were found. It is concluded that subgenotype 1b is the sole genotype HAV in this region.

  6. Serological and Molecular Investigation of Swine Hepatitis E Virus in Pigs Raised in Southern Italy.

    PubMed

    Costanzo, Nicola; Sarno, Eleonora; Peretti, Vincenzo; Ciambrone, Lucia; Casalinuovo, Francesco; Santoro, Adriano

    2015-11-01

    Hepatitis E virus (HEV) infection is a common acute hepatitis transmitted by the fecal-oral route. In developed countries, the virus has a zoonotic potential, and domestic pigs and wild boars are considered main reservoirs. To assess the prevalence of HEV-positive animals in the Calabria region (southern Italy) on a serological and molecular level, a total of 216 autochthonous healthy pigs (Apulo-Calabrese breed) were sampled. Both sera and feces were collected. Pigs were grouped based on age: 117 pigs <6 months and 99 pigs >6 months. By using a commercial enzyme-linked immunosorbent assay system, a total of 173 (80%) of the 216 pigs tested seropositive. In all sampled farms (n = 8), pigs with antibodies (immunoglobulin G) against HEV were detected at a level higher than 60%, with a significant difference among age groups (P < 0.0001). Moreover, 16 fattening pigs were found to be nested reverse transcription PCR positive and thus to shed viral genomes in their feces. These positive findings resulted in a prevalence of 48.4% on the farm level (16 of 35 pigs) and an overall prevalence of 7.4% at the animal level (16 of 216 pigs). Based on the present study, HEV seems to circulate among the autochthonous domestic pig population of southern Italy with a low sharing rate. Further studies exploring the origin of infection are needed to minimize the risk of human exposure and to reduce consequences for public health.

  7. Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance

    PubMed Central

    Dietrich, Christoph G; Götze, Oliver; Geier, Andreas

    2016-01-01

    Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma. The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function. This review summarizes the regulatory and functional changes in phase I and phase II metabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients. Interestingly, phase I enzymes are generally downregulated transcriptionally, while phase II enzymes are mostly preserved transcriptionally but are reduced in their function. Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis. Lipid and glucose metabolism are characterized by insulin resistance and catabolism, leading to the disturbance of energy expenditure and wasting. Possible non-invasive tests, especially breath tests, for components of liver metabolism are discussed. The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients. Additionally, studies in humans are rare, and species differences preclude the transferability of data from rodents to humans. In clinical practice, some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis, but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests. PMID:26755861

  8. Distribution and Molecular Characterization of Hepatitis E virus in Domestic Animals and Wildlife in Croatia.

    PubMed

    Prpić, Jelena; Černi, Silvija; Škorić, Dijana; Keros, Tomislav; Brnić, Dragan; Cvetnić, Željko; Jemeršić, Lorena

    2015-09-01

    Hepatitis E is becoming a growing health concern in European countries as an increase of sporadic human cases of unknown origin has been recorded lately. Its causative agent, Hepatitis E virus (HEV), is known to have zoonotic potential and thus the role of domestic and wild animals in the chain of viral spread should be considered when investigating risk factors and the epidemiology of the disease. A comprehensive survey based on viral RNA detection was carried out in Croatia including blood, spleen and liver samples originating from 1816 different domestic and wild animals and digestive gland samples from 538 molluscs. A high HEV prevalence was detected in domestic pigs (24.5%) and wild boars (12.3%), whereas cattle, molluscs, ruminant and carnivore wildlife samples tested negative. Molecular characterization of both ORF1 and ORF2 genomic regions confirmed the phylogenetic clustering of the obtained sequences into genotype 3, previously reported in Europe. Furthermore, our results proved the presence of identical sequence variants in different samples, regardless of their origin, age or habitat of the host, suggesting transmission events between domestic swine, as well as between domestic swine and wild boars in the country. Moreover, a close genetic relationship of Croatian animal strains and known human HEV strains from GenBank opens the question of possible cross-species HEV transmission in Croatia, especially in the areas with an intensive swine production.

  9. Effect of molecular adsorbent recirculating system in hepatitis C virus-related intractable pruritus.

    PubMed

    Doria, Cataldo; Mandalá, Lucio; Smith, Jan; Vitale, Claudio H; Lauro, Augusto; Gruttadauria, Salvatore; Marino, Ignazio R; Foglieni, Carlo Scotti; Magnone, Mario; Scott, Victor L

    2003-04-01

    Intractable pruritus is more common in cholestatic liver diseases and may be the presenting symptom and/or major complaint of hepatitis C and/or hepatitic C virus-related cirrhosis. From September 2000 to May 2002, three patients affected by intractable pruritus secondary to hepatitis C cirrhosis that failed medical treatment were treated with a molecular adsorbent recirculating system (MARS). MARS is an artificial liver support system that aims to clear the blood of metabolic waste products normally metabolized by the liver. Each patient underwent seven MARS sessions. Liver function tests, the 36-Item Short Form quality-of-life test, visual analog scale for itching, and bile acid measurement in the serum, albumin circuit and ultrafiltrate were performed before and after each MARS session. Moreover, at hospital admission, each patient underwent a psychological workup and abdominal imaging study. Subjective improvement in pruritus and quality of life, along with a decrease in serum bile acid concentration, was observed in every patient; no patient underwent retreatment and/or liver transplantation up to a 9-month follow-up. One patient died 201 days after MARS treatment. Although we observed a decreased level of serum bile acids, one cannot conclude that this was the mechanism of action for the reduction in pruritus intensity in patients in our series. Different toxins and/or a placebo effect might have had a role in this setting.

  10. Molecular Assay and Genotyping of Hepatitis C Virus among Infected Egyptian and Saudi Arabian Patients

    PubMed Central

    Farag, Mohamed MS; Sofy, Ahmed R; Mousa, Adel A; Ahmed, Mohamed A; Alganzory, Mohamed R

    2015-01-01

    Hepatitis C virus (HCV) infection is a major health problem recognized globally. HCV is a common cause of liver fibrosis that may lead to liver cirrhosis or hepatocellular carcinoma. The aim of this study was to estimate the prevalence of HCV infection and genotyping among Egyptian and Saudi Arabian chronic patients using different molecular techniques. HCV RNA viral load was assessed by real-time polymerase chain reaction (RT-PCR) technology. For HCV genotyping, RT-PCR hybridization fluorescence-based method and reverse hybridization line probe assay (INNO-LiPA) were used. A total of 40 anti-HCV-positive patients with chronic hepatitis C were examined for HCV RNA, genotyping, and different laboratory investigations. In the present study, HCV genotypes 4, mixed 4.1b, and 1 were detected in patients of both countries, while genotype 2 was only detected in Saudi Arabian patients. Genotyping methods for HCV showed no difference in the classification at the genotype level. With regard to HCV subtypes, INNO-LiPA assay was a reliable test in HCV genotyping for the detection of major genotypes and subtypes, while RT-PCR-based assay was a good test at the genotype level only. HCV genotype 4 was found to be the predominant genotype among Egyptian and Saudi Arabian chronic patients. In conclusion, data analysis for detecting and genotyping HCV was an important factor for understanding the epidemiology and treatment strategies of HCV among Egyptian and Saudi Arabian chronic patients. PMID:26512201

  11. Growth of a delta-doped silicon layer by molecular beam epitaxy on a charge-coupled device for reflection-limited ultraviolet quantum efficiency

    NASA Technical Reports Server (NTRS)

    Hoenk, Michael E.; Grunthaner, Paula J.; Grunthaner, Frank J.; Terhune, R. W.; Fattahi, Masoud; Tseng, Hsin-Fu

    1992-01-01

    Low-temperature silicon molecular beam epitaxy is used to grow a delta-doped silicon layer on a fully processed charge-coupled device (CCD). The measured quantum efficiency of the delta-doped backside-thinned CCD is in agreement with the reflection limit for light incident on the back surface in the spectral range of 260-600 nm. The 2.5 nm silicon layer, grown at 450 C, contained a boron delta-layer with surface density of about 2 x 10 exp 14/sq cm. Passivation of the surface was done by steam oxidation of a nominally undoped 1.5 nm Si cap layer. The UV quantum efficiency was found to be uniform and stable with respect to thermal cycling and illumination conditions.

  12. [Molecular aspects of the antiviral response against hepatitis C virus implicated in vaccines development].

    PubMed

    Llanes, María Soledad; Palacios, Natalia Soledad; Piccione, Magalí; Ruiz, María Guillermina; Layana, Carla

    2015-04-01

    Hepatitis C is a contagious liver disease caused by hepacivirus of the Flaviviridae family. It has a RNA genome, a unique highly variable molecule. It encodes ten proteins which are necessary to infect cells and multiply. Replication occurs only in hepatocytes. Because of its wide genomic variability and the absence of symptoms, it is difficult to make an early diagnosis and successful treatment. In this review we analyze the molecular mechanism by which the virus infects the hepatocytes and causes the disease. We focused the analysis on different therapies, with the possibility of improving treatment with the use of new specific vaccines. We highlight the use of new therapies based on nucleic acids, mainly DNA vectors. In the near future, once this treatment is adequately evaluated in clinical trials, and the costs are calculated, it could be a very beneficial alternative to conventional methods.

  13. New molecular methods for the detection of hepatitis A and Norwalk viruses in shellfish.

    PubMed

    Romalde, J L

    1996-12-01

    Outbreaks of viral enteric diseases after consumption of shellfish are a major health risk. Methodological problems (such as toxicity for cell cultures and low viral concentrations) and the unculturability of some strains (i.e. hepatitis A virus, Norwalk virus) have made it difficult to study those viruses in the environmental samples. Currently, the analysis of the hygienic quality of marketable shellfish is determined by the use of fecal indicator bacteria, but their reliability in determining viral pollution of shellfish is very low. Recent biotechnology developments are providing available rapid, sensitive, and specific tools for detecting food-borne viruses in shellfish and in shellfish-growing waters. In this paper, a review of these new molecular methods is carried out, discussing their advantages and possible applications.

  14. Hepatitis C virus molecular evolution: transmission, disease progression and antiviral therapy.

    PubMed

    Preciado, Maria Victoria; Valva, Pamela; Escobar-Gutierrez, Alejandro; Rahal, Paula; Ruiz-Tovar, Karina; Yamasaki, Lilian; Vazquez-Chacon, Carlos; Martinez-Guarneros, Armando; Carpio-Pedroza, Juan Carlos; Fonseca-Coronado, Salvador; Cruz-Rivera, Mayra

    2014-11-21

    Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to several viral and host factors. Virus molecular evolution plays an important role in HCV transmission, disease progression and therapy outcome. The high degree of genetic heterogeneity characteristic of HCV is a key element for the rapid adaptation of the intrahost viral population to different selection pressures (e.g., host immune responses and antiviral therapy). HCV molecular evolution is shaped by different mechanisms including a high mutation rate, genetic bottlenecks, genetic drift, recombination, temporal variations and compartmentalization. These evolutionary processes constantly rearrange the composition of the HCV intrahost population in a staging manner. Remarkable advances in the understanding of the molecular mechanism controlling HCV replication have facilitated the development of a plethora of direct-acting antiviral agents against HCV. As a result, superior sustained viral responses have been attained. The rapidly evolving field of anti-HCV therapy is expected to broad its landscape even further with newer, more potent antivirals, bringing us one step closer to the interferon-free era.

  15. Molecular Evolution and Phylodynamics of Acute Hepatitis B Virus in Japan

    PubMed Central

    Lin, Serena Y. C.; Toyoda, Hidenori; Kumada, Takashi; Liu, Hsin-Fu

    2016-01-01

    Hepatitis B virus (HBV) is prevalent worldwide and causes liver diseases, including acute and chronic hepatitis. Ten HBV genotypes (A–J) with distinct geographic distributions have been reported. Cases of acute HBV infection with genotype A have increased in Japan nationwide since the 1990s, mainly through sexual transmission. To investigate the molecular evolution and phylodynamics of HBV genotypes, we collected acute HBV isolates acquired in Japan from 1992–2002. Full genomes were obtained for comprehensive phylogenetic and phylodynamic analysis, with other Japanese HBV sequences from GenBank that were isolated during 1991–2010. HBV genotypes were classified using the maximum-likelihood and Bayesian methods. The GMRF Bayesian Skyride was used to estimate the evolution and population dynamics of HBV. Four HBV genotypes (A, B, C, and H) were identified, of which C was the major genotype. The phylodynamic results indicated an exponential growth between the 1960s and early 1990s; this was followed by a population bottleneck after 1995, possibly linked with successful implementation of a nationwide vaccination program. However, HBV/A increased from 1990 to 2003–2004, and then started to decrease. The prevalence of genotype A has increased over the past 10 years. Phylodynamic inference clearly demonstrates a steady population growth compatible with an ongoing subepidemic; this might be due to the loss of immunity to HBV in adolescents and people being born before the vaccination program. This is the first phylodynamic study of HBV infection in Japan and will facilitate understanding the molecular epidemiology and long-term evolutionary dynamics of this virus in Japan. PMID:27280441

  16. Diversity of anoxygenic phototrophic sulfur bacteria in the microbial mats of the Ebro Delta: a combined morphological and molecular approach.

    PubMed

    Martínez-Alonso, Maira; Van Bleijswijk, Judith; Gaju, Núria; Muyzer, Gerard

    2005-05-01

    The diversity of purple and green sulfur bacteria in the multilayered sediments of the Ebro Delta was investigated. Specific oligonucleotide primers for these groups were used for the selective amplification of 16S rRNA gene sequences. Subsequently, amplification products were separated by denaturing gradient gel electrophoresis and sequenced, which yielded a total of 32 sequences. Six of the sequences were related to different cultivated members of the green sulfur bacteria assemblage, whereas seven fell into the cluster of marine or halophilic Chromatiaceae. Six sequences were clustered with the family Ectothiorhodospiraceae, three of the six being closely related to chemotrophic bacteria grouped together with Halorhodospira genus, and the other three forming a group related to the genus Ectothiorhodospira. The last thirteen sequences constituted a cluster where no molecular isolate from microbial mats has so far been reported. Our results indicate that the natural diversity in the ecosystem studied has been significantly underestimated in the past and point out the presence of novel species not related to all known purple sulfur bacteria. Furthermore, the detection of green sulfur bacteria, after only an initial step of enrichment, suggests that -- with the appropriate methodology -- several genera, such as Prosthecochloris, could be established as regular members of marine microbial mats.

  17. Source Apportionment of Background PAHs in the Peace-Athabasca Delta (Alberta, Canada) Using Molecular Level Radiocarbon Analysis.

    PubMed

    Jautzy, Josué J; Ahad, Jason M E; Hall, Roland I; Wiklund, Johan A; Wolfe, Brent B; Gobeil, Charles; Savard, Martine M

    2015-08-04

    The downstream accumulation of polycyclic aromatic hydrocarbons (PAHs) in the Peace-Athabasca Delta (PAD), an ecologically important landscape, is a key issue of concern given the rapid development of the oil sands industry in Northern Alberta, Canada. In addition to PAHs derived from industrial activity (i.e., oil sands mining) within the Athabasca watershed, however, forest fires and erosion of fossil fuel deposits within both the Athabasca and Peace watersheds are two potentially important natural sources of PAHs delivered to the PAD. Consequently, evaluating the environmental impact of mining activities requires a quantitative understanding of natural, background PAHs. Here, we utilize molecular-level natural-abundance radiocarbon measurements on an amalgamated sediment record from a Peace River flood-susceptible oxbow lake in the northern Peace sector of the PAD to quantitatively discriminate sources of naturally occurring alkylated PAHs (fossil and modern biomass). A radiocarbon mass balance quantified a predominantly natural petrogenic source (93% petrogenic, 7% forest fire) for alkylated PAHs during the past ∼50 years. Additionally, a significant petrogenic component determined for retene, a compound usually considered a biomarker for softwood combustion, suggests that its use as a unique forest fire indicator may not be suitable in PAD sediments receiving Peace watershed-derived fluvial inputs.

  18. Molecular status of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus among transgender commercial sex workers in Surakarta, Indonesia

    NASA Astrophysics Data System (ADS)

    Prasetyo, Afiono Agung; Sari, Yulia; Dharmawan, Ruben; Marwoto

    2017-02-01

    Sexual contact and other risk behavior among transgender working as commercial sex workers are important factors for sexual and blood-borne virus (BBV) infections. However, there no data concerning the molecular status of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) circulated among transgender working as commercial sex workers. Blood samples obtained from transgender working as commercial sex workers in Surakarta were examined for HIV antibodies, HBsAg and HCV antibodies, respectively, by immunological assays. All blood samples were also subjected for viral nucleic acid extraction and molecular detection of HIV, HBV and HCV by nested RT-PCR. The PCR products were purified from agarose gels, and the nucleotide sequences were retrieved and molecular analyzed. HIV, HBV and HCV was detected in 26.9% (7/26), 19.2% (5/26) and 46.2% (12/26), respectively. HIV CRF01_AE and B were found to be circulating in the community. HBV genotype B3 predominated, followed by C1. HCV genotype 1a predominated among HCV-infected transgender working as commercial sex workers, followed by 1c, 3a, and 4a. HIV, HBV, and HCV were found circulating in the transgender working as commercial sex workers in Surakarta, Indonesia.

  19. Molecular and Contextual Markers of Hepatitis C Virus and Drug Abuse

    PubMed Central

    Shapshak, Paul; Somboonwit, Charurut; Drumright, Lydia N.; Frost, Simon D.W.; Commins, Deborah; Tellinghuisen, Timothy L.; Scott, William K.; Duncan, Robert; McCoy, Clyde; Page, J. Bryan; Giunta, Brian; Fernandez, Francisco; Singer, Elyse; Levine, Andrew; Minagar, Alireza; Oluwadara, Oluwadayo; Kotila, Taiwo; Chiappelli, Francesco; Sinnott, John T.

    2015-01-01

    The spread of hepatitis C virus (HCV) infection involves a complex interplay of social risks, and molecular factors of both virus and host. Injection drug abuse is the most powerful risk factor for HCV infection, followed by sexual transmission and additional non-injection drug abuse factors such as co-infection with other viruses and barriers to treatment. It is clearly important to understand the wider context in which the factors related to HCV infection occur. This understanding is required for a comprehensive approach leading to the successful prevention, diagnosis, and treatment of HCV. An additional consideration is that current treatments and advanced molecular methods are generally unavailable to socially disadvantaged patients. Thus, the recognition of behavioral/social, viral, and host factors as components of an integrated approach to HCV is important to help this vulnerable group. Equally important, this approach is key to the development of personalized patient treatment – a significant goal in global healthcare. In this review, we discuss recent findings concerning the impact of drug abuse, epidemiology, social behavior, virology, immunopathology, and genetics on HCV infection and the course of disease. PMID:19650670

  20. A molecular thermodynamic model for the stability of hepatitis B capsids

    SciTech Connect

    Kim, Jehoon; Wu, Jianzhong

    2014-06-21

    Self-assembly of capsid proteins and genome encapsidation are two critical steps in the life cycle of most plant and animal viruses. A theoretical description of such processes from a physiochemical perspective may help better understand viral replication and morphogenesis thus provide fresh insights into the experimental studies of antiviral strategies. In this work, we propose a molecular thermodynamic model for predicting the stability of Hepatitis B virus (HBV) capsids either with or without loading nucleic materials. With the key components represented by coarse-grained thermodynamic models, the theoretical predictions are in excellent agreement with experimental data for the formation free energies of empty T4 capsids over a broad range of temperature and ion concentrations. The theoretical model predicts T3/T4 dimorphism also in good agreement with the capsid formation at in vivo and in vitro conditions. In addition, we have studied the stability of the viral particles in response to physiological cellular conditions with the explicit consideration of the hydrophobic association of capsid subunits, electrostatic interactions, molecular excluded volume effects, entropy of mixing, and conformational changes of the biomolecular species. The course-grained model captures the essential features of the HBV nucleocapsid stability revealed by recent experiments.

  1. A molecular thermodynamic model for the stability of hepatitis B capsids

    NASA Astrophysics Data System (ADS)

    Kim, Jehoon; Wu, Jianzhong

    2014-06-01

    Self-assembly of capsid proteins and genome encapsidation are two critical steps in the life cycle of most plant and animal viruses. A theoretical description of such processes from a physiochemical perspective may help better understand viral replication and morphogenesis thus provide fresh insights into the experimental studies of antiviral strategies. In this work, we propose a molecular thermodynamic model for predicting the stability of Hepatitis B virus (HBV) capsids either with or without loading nucleic materials. With the key components represented by coarse-grained thermodynamic models, the theoretical predictions are in excellent agreement with experimental data for the formation free energies of empty T4 capsids over a broad range of temperature and ion concentrations. The theoretical model predicts T3/T4 dimorphism also in good agreement with the capsid formation at in vivo and in vitro conditions. In addition, we have studied the stability of the viral particles in response to physiological cellular conditions with the explicit consideration of the hydrophobic association of capsid subunits, electrostatic interactions, molecular excluded volume effects, entropy of mixing, and conformational changes of the biomolecular species. The course-grained model captures the essential features of the HBV nucleocapsid stability revealed by recent experiments.

  2. Molecular mechanism of hepatitis B virus (HBV) on suppression of raf kinase inhibitor protein (RKIP) expression

    PubMed Central

    Cheng, Xiao-Ke; Yu, Guo-Zheng; Li, Xiao-Dong; Ren, Xue-Qun

    2017-01-01

    Raf kinase inhibitor protein (RKIP) has been shown to be a suppressor of the mitogen-activated protein kinase pathway and is reported to be involved in human malignancy. However, the molecular mechanism of hepatitis B virus (HBV) in regulating RKIP expression is not yet clarified. In this study, we compared RKIP expression in 107 pairs of matched liver cancer and adjacent non-cancerous liver tissues. Among seven HBV-encoded proteins, we found HBV X (HBX) protein could significantly inhibit the expression level of RKIP, indicating that HBV could suppress RKIP expression through regulating HBX. To further elucidate the mechanism, analyses on transcriptional regulation and promoter methylation inhibition were conducted in Huh7 cells. Our results showed that HBX can interact with AP1 protein to inhibit the RKIP transcription. Moreover, we observed that the promoter methylation level of RKIP could be enhanced by HBV. In conclusion, our study revealed that RKIP could act as a molecular marker for HBV-infected liver cancer, but had no tumor-suppressing effect. PMID:27902472

  3. Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis

    SciTech Connect

    Kato, Nobuyuki; Hijikata, Makoto; Ootsuyama, Yuko; Nakagawa, Masanori; Ohkoshi, Showgo; Sugimura, Takashi; Shimotohno, Kunitada )

    1990-12-01

    The nucleotide sequence of the Japanese type of hepatitis C virus (HCV-J) genome, consisting of 9413 nucleotides, was determined by analyses of cDNA clones from plasma specimens from Japanese patients with chronic hepatitis. HCV-J genome contains a long open reading frame that can encode a sequence of 3010 amino acid residues. Comparison of HCV-J with the American isolate of HCV showed 22.6% difference in nucleotide sequence and 15.1% difference in amino acid sequence. Thus HCV-J and the American isolate of HCV are probably different subtypes of HCV. The relationship of HCV-J with other animal RNA virus families and the putative organization of the HCV-J genome are discussed.

  4. Decreased hepatic contents of coenzyme A molecular species in mice after subchronic mild social defeat stress.

    PubMed

    Kubota, Yoshifumi; Goto, Tatsuhiko; Hagiya, Yuki; Chohnan, Shigeru; Toyoda, Atsushi

    2016-01-01

    Social stress may precipitate psychiatric disorders such as depression, which is related to the occurrence of the metabolic syndrome, including obesity and type 2 diabetes. We have evaluated the effects of social stress on central and peripheral metabolism using a model of depression in mice. In the present study, we focused on coenzyme A (CoA) molecular species [i.e. non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA] which play important roles in numerous metabolic pathways, and we analyzed changes in expression of these molecules in the hypothalamus and liver of adult male mice (C57BL/6J) subjected to 10 days of subchronic mild social defeat stress (sCSDS) with ICR mice as aggressors. Mice (n = 12) exposed to showed hyperphagia- and polydipsia-like symptoms and increased body weight gain compared with control mice which were not affected by exposure to ICR mice (n = 12). To elucidate the underlying metabolic features in the sCSDS model, acetyl-CoA, malonyl-CoA and CoASH tissue levels were analyzed using the acyl-CoA cycling method. The levels of hypothalamic malonyl-CoA, which decreases feeding behavior, were not influenced by sCSDS. However, sCSDS reduced levels of acetyl-CoA, malonyl-CoA and total CoA (sum of the three CoA molecular species) in the liver. Hence, hyperphagia-like symptoms in sCSDS mice evidently occurred independently of hypothalamic malonyl-CoA, but might consequently lead to down-regulation of hepatic CoA via altered expression of nudix hydrolase 7. Future studies should investigate the molecular mechanism(s) underlying the down-regulation of liver CoA pools in sCSDS mice.

  5. Molecular Survey of Hepatitis C Virus in the Touristic City of Mar Del Plata, Argentina

    PubMed Central

    Culasso, Andrés C. A.; Elizalde, Mercedes; Campos, Rodolfo H.; Barbini, Luciana

    2012-01-01

    The global epidemiology of Hepatitis C Virus (HCV) may be roughly described by two groups of genotypes: the worldwide distributed ones (subtypes 1a, 1b, 2a and 3a, among others) and the endemic ones (subtypes 4a, 5a, 6a, among others). Epidemiological and population dynamic studies of the worldwide distributed genotypes have shown that subtypes 1a and 3a are common among intravenous drug users (IDUs) and that they are also in expansion in some countries. The molecular survey of HCV provides some clues about the epidemiological status of the infections in a local scale and the phylogenetic and demographic reconstruction analyses complement this study by inferring whether the infections of certain subtypes are in a steady state or expanding. Here, a molecular survey of the HCV variants that circulate in the touristic city of Mar del Plata (Buenos Aires, Argentina) was performed in samples obtained from 42 patients. The subtypes detected were 1a (32 patients), 3a (8 patients) and 1b (2 patients). The demographic history of subtype 1a inferred using the sequence data showed an exponential growth in the 1990′s. The period of viral expansion was delayed compared with that observed for the same genotype in other countries where the transmission was associated with IDUs. Also, the phylogeographic analysis of HCV-1a showed a statistically significant association between the location of the samples and the phylogeny, which may be the result of the local transmission of HCV in the city. The molecular analysis helped in the description of the complex epidemiological context of a touristic city, and pointed out that some sanitary measures should be taken in order to reduce the transmission of HCV (and maybe of HIV) among IDUs. PMID:23028605

  6. Molecular characterization of the human delta-aminolevulinate dehydratase 2 (ALAD2) allele: implications for molecular screening of individuals for genetic susceptibility to lead poisoning.

    PubMed Central

    Wetmur, J G; Kaya, A H; Plewinska, M; Desnick, R J

    1991-01-01

    The second enzyme in the heme biosynthetic pathway, delta-aminolevulinate dehydratase (ALAD), is a homooctameric protein encoded by a gene localized to human chromosome 9q34. Expression of the two common alleles, ALAD1 (p = .9) and ALAD2 (q = .1), results in a polymorphic enzyme system with three distinct charge isozymes, designated 1-1, 1-2, and 2-2. Individuals heterozygous (2pq = .18) or homozygous (q2 = .01) for the ALAD2 allele have significantly higher blood lead levels than do ALAD1 homozygotes, when exposed to low or high levels of lead in the environment. To investigate the molecular nature of this common polymorphism, total RNA from an ALAD2 homozygote was oligo-dT primed and reverse transcribed, and then the ALAD2 cDNA was amplified, subcloned, and sequenced. Compared with the ALAD1 sequence, the only difference in the ALAD2 cDNA was a G-to-C transversion of nucleotide 177 in the coding region, which created an MspI restriction site. This base substitution predicted the replacement of a positively charged lysine by a neutral asparagine (K59N), an amino acid change consistent with the more electronegative charge of the ALAD-2 subunit. The ALAD1 and ALAD2 alleles were easily detected by amplification of a 916-bp region of genomic DNA and MspI digestion which results in 582- and 511-bp products, respectively. Molecular analysis of 85 ALAD1/ALAD2 heterozygotes and of eight ALAD2 homozygotes revealed no discrepancy between the predicted genotype and the erythrocyte isozyme phenotype, indicating that all the ALAD2 alleles analyzed had the G-to-C transversion.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 PMID:1716854

  7. [The hepatitis A virus: structural and functional organization of the genome, its molecular diagnostic value and cultivation].

    PubMed

    Bondarenko, T Iu; Ternovoĭ, V A; Netesov, S V

    2013-01-01

    The analysis of recently published data on hepatitis A virus (HAV) genome clinical features, molecular diagnostic value and cell culture propagation are reviewed. The growing need in the study of the genetic diversity of HAV isolates and the search of its possible new antigenic variants are underlined. The results of the cultivation of different HAV strains are analyzed for possible application in vaccine and diagnostic kit production.

  8. Nile Delta

    Atmospheric Science Data Center

    2013-04-15

    article title:  The Nile River Delta     View Larger Image ... of eastern Africa. At the apex of the fertile Nile River Delta is the Egyptian capital city of Cairo. To the west are the Great Pyramids ...

  9. Heart transplantation in patients with chronic hepatitis B: clinical evolution, molecular analysis, and effect of treatment.

    PubMed

    Zampino, Rosa; Marrone, Aldo; Ragone, Enrico; Costagliola, Loredana; Cirillo, Grazia; Karayiannis, Peter; Ruggiero, Giuseppe; Utili, Riccardo

    2005-11-15

    We evaluated clinical evolution and hepatitis B virus (HBV) molecular changes in heart recipients with chronic HBV infection before transplantation, and studied the effects of lamivudine treatment in patients who experienced HBV reactivation. Nine patients with chronic HBV infection who underwent heart transplantation were investigated. HBV surface/core-promoter/precore/core regions were sequenced. Prior to transplantation, all nine patients had consistently normal ALT and low HBV-DNA levels. Seven experienced HBV reactivation after transplantation (ALT elevated, HBV-DNA>200.000 cps/ml). Lamivudine treatment was initially effective in all patients; three patients during the second year of treatment developed lamivudine resistance-associated mutations (rt-L180M, rt-M204V) with severe disease reactivation, remitted after switch to adefovir treatment. No other significant HBV mutations were identified in the genomic regions studied. Immune suppression is crucial in the reactivation of previous inactive HBV infection and in the liver disease progression in heart recipients. Preemptive lamivudine treatment could be useful in the early management of these patients.

  10. Computational model of hepatitis B virus DNA polymerase: Molecular dynamics and docking to understand resistant mutations

    PubMed Central

    Daga, Pankaj R; Duan, Jinsong; Doerksen, Robert J

    2010-01-01

    Hepatitis B virus (HBV) DNA polymerase (HDP) is a pharmacological target of intense interest. Of the seven agents approved in USA for the treatment of HBV infections, five are HDP inhibitors. However, resistance development against HDP inhibitors, such as lamivudine and adefovir, has severely hurt their efficacy to treat HBV. As a step toward understanding the mechanism of resistance development and for gaining detailed insights about the active site of the enzyme, we have built a homology model of HDP which is an advance over previously reported ones. Validation using various techniques, including PROSTAT, PROCHECK, and Verify-3D profile, proved the model to be stereochemically significant. The stability of the model was studied using a 5 ns molecular dynamics simulation. The model was found to be sufficiently stable after the initial 2.5 ns with overall root mean squared deviation (RMSD) of 4.13 Å. The homology model matched the results of experimental mutation studies of HDP reported in the literature, including those of antiviral-resistant mutations. Our model suggests the significant role of conserved residues, such as rtLys32, in binding of the inhibitors, contrary to previous studies. The model provides an explanation for the inactivity of some anti-HIV molecules which are inactive against HDP. Conformational changes which occurred in certain binding pocket amino acids helped to explain the better binding of some of the inhibitors in comparison to the substrates. PMID:20162615

  11. Molecular diagnosis of Eimeria stiedae in hepatic tissue of experimentally infected rabbits.

    PubMed

    Hassan, Khaled M; Arafa, Waleed M; Mousa, Waheed M; Shokier, Khaled A M; Shany, Salama A; Aboelhadid, Shawky M

    2016-10-01

    The early detection of Eimeria stiedae in the hepatic tissue of experimentally infected rabbits was investigated using molecular assay. Forty 6-week-old male New Zealand rabbits were divided into two groups. Group A (30 animals) was infected with 2.5 × 10(4) sporulated oocysts of E. stiedae per animal on Day 0 and Group B (10 animals) was used as the uninfected controls. Three animals from Group A and one from Group B were sacrificed at 0, 3, 6, 9, 12, 15, 18, 21, 24 and 27 days post infection (PI). Gross and microscopic post-mortem findings were recorded. Polymerase chain reaction (PCR) of the E. stiedae internal transcribed spacer 1 genomic region was conducted on blood, liver tissue, and feces from the Group A experimentally infected animals. Macroscopically, the liver showed irregular yellowish white nodules pathognomonic to E. stiedae infection beginning on Day 15 PI. Hepatomegaly and ascites were obvious from Day 21-24 PI. The presence of different E. stiedae schizonts and gametocytes in the histopathological sections of the biliary epithelium were evident on Day 15 PI. The E. stiedae PCR was first positive in liver tissues on Day 12 and in fecal samples on Day 18 PI, but the blood samples were negative. In conclusion, the PCR can be used for early diagnosis and control of E. stiedae schizonts before shedding of the oocysts in feces.

  12. Volga Delta

    Atmospheric Science Data Center

    2013-04-17

    article title:  Volga Delta and the Caspian Sea     View ... appear reddish. A small cloud near the center of the delta separates into red, green, and blue components due to geometric parallax ... include several linear features located near the Volga Delta shoreline. These long, thin lines are artificially maintained shipping ...

  13. A novel virus-like particle based on hepatitis B core antigen and substrate-binding domain of bacterial molecular chaperone DnaK.

    PubMed

    Wang, Xue Jun; Gu, Kai; Xiong, Qi Yan; Shen, Liang; Cao, Rong Yue; Li, Ming Hui; Li, Tai Ming; Wu, Jie; Liu, Jing Jing

    2009-12-09

    Hepatitis B virus core (HBc) protein has been proved to be an attractive carrier for foreign epitopes, and can display green fluorescent protein (GFP) on its surface. The structure of substrate-binding domain of DnaK [DnaK (394-504 aa), DnaK SBD] is similar to GFP, we therefore reasoned that DnaK SBD might also be tolerated. Electron microscopic observations suggested that the chimeric proteins containing the truncated HBc (HBcDelta) and DnaK SBD could self-assemble into virus-like particle (VLP). Then the accessibility of DnaK SBD and the adjuvanticity of VLP HBcDelta-SBD were demonstrated by two recombinant peptide vaccines against gonadotropin-releasing hormone (GnRH), GhM and GhMNR. The latter carries in addition the peptide motif NRLLLTG which is known to bind to DnaK and DnaK SBD. The combination of VLP HBcDelta-SBD and GhMNR elicited stronger humoral responses and caused further testicular atrophy than the combinations of VLP HBcDelta and GhMNR or VLP HBcDelta-SBD and GhM in Balb/c mice. These findings indicate VLP HBcDelta-SBD might serve as an excellent carrier for GhMNR and some other peptide vaccines.

  14. Proof by EPR spectroscopy that the unpaired electron in an Os(2)(7+) species is in a delta* metal-based molecular orbital.

    PubMed

    Cotton, F Albert; Chiarella, Gina M; Dalal, Naresh S; Murillo, Carlos A; Wang, Zhenxing; Young, Mark D

    2010-01-04

    Variable temperature structural and EPR studies are reported on the paddlewheel compound [Os(2)(hpp)(4)Cl(2)]PF(6), 1, (hpp = the anion of the bicyclic guanidine 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) that contains a rare M(2)(7+) species, with the goal of determining whether the unpaired electron resides in a metal- or ligand-based molecular orbital. Crystallographic studies show that the Os-Os distance in 1 remains essentially unchanged from 213 to 30 K, which is consistent with no changes in electronic structure in this range of temperature. It is noteworthy that the metal-metal distance in 1 is about 0.05 A shorter than that in the precursor Os(2)(hpp)(4)Cl(2), which is consistent with the loss of an electron in a delta* orbital. EPR spectra of 1 were measured in dilute frozen solution, powder, and single crystals. The spectra were observable only below about 50 K, with an exceptionally large line width, approximately 3,750 gauss, for a powdered sample, due to dipolar interactions and to short relaxation times. There is a very small average g value of approximately 0.750 and a cylindrical symmetry about the Os-Os bond. These data are consistent with the unpaired electron orbital having a large L value, such as that of a delta* orbital. The combination of X-ray structural data, the short relaxation time, and the magnetic data provide strong evidence that the unpaired electron in this nine-electron Os(2)(7+) species is localized in a metal-based orbital with this electron residing predominantly in a delta* orbital rather than in a pi* orbital and, thus, having an electronic configuration of sigma(2)pi(4)delta(2)delta*.

  15. Linking molecular biomarkers with higher level condition indicators to identify effects of copper exposures on the endangered delta smelt (Hypomesus transpacificus).

    PubMed

    Connon, Richard E; Beggel, Sebastian; D'Abronzo, Leandro S; Geist, Juergen P; Pfeiff, Janice; Loguinov, Alexander V; Vulpe, Christopher D; Werner, Inge

    2011-02-01

    The delta smelt (Hypomesus transpacificus) is an endangered pelagic fish species endemic to the Sacramento-San Joaquin estuary (CA, USA), and considered an indicator of ecosystem health. Copper is a contaminant of concern in Californian waterways that may affect the development and survival of this endangered species. The experimental combination of molecular biomarkers with higher level effects may allow for interpretation of responses in a functional context that can be used to predict detrimental outcomes caused by exposure. A delta smelt microarray was developed and applied to screen for candidate molecular biomarkers that may be used in monitoring programs. Functional classifications of microarray responses were used along with quantitative polymerase chain reaction determining effects upon neuromuscular, digestive, and immune responses in Cu-exposed delta smelt. Differences in sensitivity were measured between juveniles and larvae (median lethal concentration = 25.2 and 80.4 µg/L Cu(2+), respectively). Swimming velocity declined with higher exposure concentrations in a dose-dependent manner (r =  -0.911, p < 0.05), though was not statistically significant to controls. Genes encoding for aspartoacylase, hemopexin, α-actin, and calcium regulation proteins were significantly affected by exposure and were functionally interpreted with measured swimming responses. Effects on digestion were measured by upregulation of chitinase and downregulation of amylase, whereas downregulation of tumor necrosis factor indicated a probable compromised immune system. Results from this study, and many others, support the use of functionally characterized molecular biomarkers to assess effects of contaminants in field scenarios. We thus propose that to attribute environmental relevance to molecular biomarkers, research should concentrate on their application in field studies with the aim of assisting monitoring programs.

  16. DEVELOPMENT OF A MOLECULAR METHOD TO IDENTIFY HEPATITIS E VIRUS IN WATER

    EPA Science Inventory

    Hepatitis E virus (HEV) causes an infectious form of hepatitis associated with contaminated water. By analyzing the sequence of several HEV isolates, a reverse transciption-polymerase chain reaction method was developed and optimized that should be able to identify all of the kn...

  17. 3D-QSAR and molecular docking studies on designing inhibitors of the hepatitis C virus NS5B polymerase

    NASA Astrophysics Data System (ADS)

    Li, Wenlian; Si, Hongzong; Li, Yang; Ge, Cuizhu; Song, Fucheng; Ma, Xiuting; Duan, Yunbo; Zhai, Honglin

    2016-08-01

    Viral hepatitis C infection is one of the main causes of the hepatitis after blood transfusion and hepatitis C virus (HCV) infection is a global health threat. The HCV NS5B polymerase, an RNA dependent RNA polymerase (RdRp) and an essential role in the replication of the virus, has no functional equivalent in mammalian cells. So the research and development of efficient NS5B polymerase inhibitors provides a great strategy for antiviral therapy against HCV. A combined three-dimensional quantitative structure-activity relationship (QSAR) modeling was accomplished to profoundly understand the structure-activity correlation of a train of indole-based inhibitors of the HCV NS5B polymerase to against HCV. A comparative molecular similarity indices analysis (COMSIA) model as the foundation of the maximum common substructure alignment was developed. The optimum model exhibited statistically significant results: the cross-validated correlation coefficient q2 was 0.627 and non-cross-validated r2 value was 0.943. In addition, the results of internal validations of bootstrapping and Y-randomization confirmed the rationality and good predictive ability of the model, as well as external validation (the external predictive correlation coefficient rext2 = 0.629). The information obtained from the COMSIA contour maps enables the interpretation of their structure-activity relationship. Furthermore, the molecular docking study of the compounds for 3TYV as the protein target revealed important interactions between active compounds and amino acids, and several new potential inhibitors with higher activity predicted were designed basis on our analyses and supported by the simulation of molecular docking. Meanwhile, the OSIRIS Property Explorer was introduced to help select more satisfactory compounds. The satisfactory results from this study may lay a reliable theoretical base for drug development of hepatitis C virus NS5B polymerase inhibitors.

  18. Mitochondrial Damage-Associated Molecular Patterns (MTDs) Are Released during Hepatic Ischemia Reperfusion and Induce Inflammatory Responses.

    PubMed

    Hu, Qianni; Wood, Caroline Ruth; Cimen, Sanem; Venkatachalam, Ananda Baskaran; Alwayn, Ian Patrick Joseph

    2015-01-01

    Ischemia / reperfusion injury (IRI) during the course of liver transplantation enhances the immunogenicity of allografts and thus impacts overall graft outcome. This sterile inflammatory insult is known to activate innate immunity and propagate organ damage through the recognition of damage-associate molecular pattern (DAMP) molecules. The purpose of the present study was to investigate the role of mitochondrial DAMPs (MTDs) in the pathogenesis of hepatic IRI. Using in vitro models we observed that levels of MTDs were significantly higher in both transplantation-associated and warm IR, and that co-culture of MTDs with human and rat hepatocytes significantly increased cell death. MTDs were also released in an in vivo rat model of hepatic IRI and associated with increased secretion of inflammatory cytokines (TNF-α, IL-6, and IL-10) and increased liver injury compared to the sham group. Our results suggest that hepatic IR results in a significant increase of MTDs both in vitro and in vivo suggesting that MTDs may serve as a novel marker in hepatic IRI. Co-culture of MTDs with hepatocytes showed a decrease in cell viability in a concentration dependent manner, which indicates that MTDs is a toxic mediator participating in the pathogenesis of liver IR injury.

  19. Genotype Distribution and Molecular Epidemiology of Hepatitis C Virus in Hubei, Central China

    PubMed Central

    Peng, Jing; Lu, Yanjun; Liu, Weiyong; Zhu, Yaowu; Yan, Xiaoling; Xu, Jingxin; Wang, Xiong; Wang, Yue; Liu, Wei; Sun, Ziyong

    2015-01-01

    Background Little is known about the molecular epidemiology of hepatitis C virus (HCV) infection in Central China. Methodology/Principal Findings A total of 570 patients from Hubei Province in central China were enrolled. These patients were tested positive for HCV antibody prior to blood transfusion. Among them, 177 were characterized by partial NS5B and/or Core-E1 sequences and classified into five subtypes: 1b, 83.0% (147/177); 2a, 13.0% (23/177); 3b, 2.3% (4/177); 6a, 1.1% (2/177); 3a, 0.6% (1/177). Analysis of genotype-associated risk factors revealed that paid blood donation and transfusion before 1997 were strongly associated with subtypes 1b and 2a, while some subtype 2a cases were also found in individuals with high risk sexual behaviors; subtypes 3b, 6a, and 3a were detected only in intravenous drug users. Phylogeographic analyses based on the coalescent datasets demonstrated that 1b, 2a, 3b, and 6a were locally epidemic in Hubei Province. Among them, subtype 1b Hubei strains may have served as the origins of this subtype in China, and 2a and 3b Hubei strains may have descended from the northwest and southwest of China, respectively, while 6a Hubei strains may have been imported from the central south and southwest. Conclusion/Significance The results suggest that the migration patterns of HCV in Hubei are complex and variable among different subtypes. Implementation of mandatory HCV screening before donation has significantly decreased the incidence of transfusion-associated HCV infection since 1997. More attention should be paid to intravenous drug use and unsafe sexual contact, which may have become new risk factors for HCV infection in Hubei Province. PMID:26325070

  20. Molecular Mechanisms Involved in the Interaction Effects of Alcohol and Hepatitis C Virus in Liver Cirrhosis

    PubMed Central

    Mas, Valeria R; Fassnacht, Ryan; Archer, Kellie J; Maluf, Daniel

    2010-01-01

    The mechanisms by which alcohol consumption accelerates liver disease in patients with chronic hepatitis C virus (HCV) are not well understood. To identify the characteristics of molecular pathways affected by alcohol in HCV patients, we fit probe-set level linear models that included the additive effects as well as the interaction between alcohol and HCV. The study included liver tissue samples from 78 patients, 23 (29.5%) with HCV-cirrhosis, 13 (16.7%) with alcohol-cirrhosis, 23 (29.5%) with HCV/alcohol cirrhosis and 19 (24.4%) with no liver disease (no HCV/no alcohol group). We performed gene-expression profiling by using microarrays. Probe-set expression summaries were calculated by using the robust multiarray average. Probe-set level linear models were fit where probe-set expression was modeled by HCV status, alcohol status, and the interaction between HCV and alcohol. We found that 2172 probe sets (1895 genes) were differentially expressed between HCV cirrhosis versus alcoholic cirrhosis groups. Genes involved in the virus response and the immune response were the more important upregulated genes in HCV cirrhosis. Genes involved in apoptosis regulation were also overexpressed in HCV cirrhosis. Genes of the cytochrome P450 superfamily of enzymes were upregulated in alcoholic cirrhosis, and 1230 probe sets (1051 genes) had a significant interaction estimate. Cell death and cellular growth and proliferation were affected by the interaction between HCV and alcohol. Immune response and response to the virus genes were downregulated in HCV-alcohol interaction (interaction term alcohol*HCV). Alcohol*HCV in the cirrhotic tissues resulted in a strong negative regulation of the apoptosis pattern with concomitant positive regulation of cellular division and proliferation. PMID:20386865

  1. Genotyping and molecular characterization of hepatitis B virus in liver disease patients in Kenya.

    PubMed

    Ochwoto, Missiani; Chauhan, Ranjit; Gopalakrishnan, Deepak; Chen, Chien-Yu; Ng'ang'a, Zipporah; Okoth, Fredrick; Kioko, Henry; Kimotho, James; Kaiguri, Peter; Kramvis, Anna

    2013-12-01

    Hepatitis B virus (HBV) genotypes are important in both the clinical manifestation of disease and treatment response. Although Kenya belongs to the African Region (AFR-E) characterized by high mortality and hyperendemicity of HBV, there is a paucity of HBV genotyping data. The aim of this study was to molecularly characterize the basic core promoter/precore (BCP/PC) and complete surface (S) regions of HBV isolated from 61 HBsAg-positive liver disease patients attending Kenyatta National Hospital in Nairobi. HBsAg, HBeAg and viral loads were determined. HBV DNA was amplified and sequenced from 58/61 patients. In addition to the complete genome of two isolates, the BCP/PC and the complete S regions of 43 and 38 isolates, respectively were sequenced. Following phylogenetic analysis of the S region, 38 isolates clustered with subgenotype A1, whereas two isolates clustered with genotype D, one with subgenotype D1 and another as an outlier of the clade containing subgenotype D6 and the D/E recombinant. When the complete genome of the latter isolate was sequenced it clustered with D6. The majority of isolates belonged to serological subtype adw2 and only four to ayw2. Three distinct groups of subgenotype A1, distinguished by different amino acid motifs, circulate in Kenya: two in the African cluster and a monophyletic clade in the "Asian" cluster. HBeAg-negativity was a result of G1896A in genotype D isolates, whereas in subgenotype A1, the HBeAg-negativity was a result of mutations in the Kozak region (1809-1812) or precore start codon (1814-1816). Mutations at positions 1762 and 1764 occurred more frequently in HCC patients (p<0.05). In conclusion, subgenotypes A1, D1 and D6 circulate in liver disease patients in Kenya, with A1 predominating.

  2. Molecular characteristics of a novel strain of canine minute virus associated with hepatitis in a dog.

    PubMed

    Choi, Jeong-Won; Jung, Ji-Youl; Lee, Jae-Il; Lee, Kyoung-Ki; Oem, Jae-Ku

    2016-08-01

    A 5-year-old female Yorkshire terrier dog died a few days following hernia and ovariohysterectomy surgeries. Necropsy performed on the dog revealed that the surgeries were not the cause of death; however, degenerative viral hepatitis, showing intranuclear inclusion bodies in hepatic cells, was observed in histopathologic examination. Several diagnostic methods were used to screen for the cause of disease, and minute virus of canines (MVC) was detected in all parenchymal organs, including the liver. Other pathogens that may cause degenerative viral hepatitis were not found. Infection with MVC was confirmed by in situ hybridization, which revealed the presence of MVC nucleic acid in the liver tissue of the dog. Through sequencing and phylogenetic analysis of the nearly complete genome sequence, the strain was found to be distinct from other previously reported MVC strains. These results indicate that this novel MVC strain might be related to degenerative viral hepatitis in dogs.

  3. [Comparison of two commercial molecular assays for quantitative measurement of hepatitis B viral DNA].

    PubMed

    Zalewska, Małgorzata; Domagała, Małgorzata; Gładysz, Andrzej

    2003-12-01

    The detection and quantification of hepatitis B virus (HBV) genomes appear to be the most reliable method for monitoring HBV infection and assessing responses to antiviral treatment. For quantitative determination of HBV viremia molecular biology-based assays are used. The aim of this study was to compare and evaluate the performance of two HBV DNA detection and quantification commercial assays: hybrid-capture Digene Hybrid Capture HBV DNA assays and based on competitive polymerase chain reaction (PCR) Cobas Amplicor HBV Monitor Roche Diagnostics. Reproducibility, linearity, sensitivity were determined with 2-fold dilution series of high-titers samples and with 113 sera samples from patients with chronic HBV infection. Within-run and between-run coefficients of variation ranged from 2.4-9.7% for hybrid-capture and from 3.7-15% for PCR-based Monitor. The hybrid-capture and PCR Monitor assays appeared to be linear throughout their range of quantification: 5-2000 pg/ml and 2 x 10(2)-2 x 10(5) copies/ml respectively. The HBV DNA units used in the two assays were not comparable. Hybrid-capture and Monitor gave concordant results with 87 (82.1%) of 106 samples. The assays were both positive with 79 (74.5%) samples and were negative in 7 (7.5%) cases. Hybrid-capture and Monitor gave discordant results in 17 (17.9%) cases. The Monitor Assay was positive in 13 (61.9%) of the 21 samples negative in hybrid-capture. The competitive PCR-based Monitor assay appear to be significantly more sensitive but slightly less reproducible than the hybrid-capture. In the group of patients with seroconversion to anti-HBe PCR method should be used for measurement of viral load. In the presence of HBe antigen concentration of HBV DNA may be tested by hybrid-capture assay. Also these two assays may be used in complementary fashion in the management of HBV infected patients. It seems reasonable to use a hybrid-capture assay first, because its linear range of quantification is extended to high

  4. Delta-doping of Semiconductors

    NASA Astrophysics Data System (ADS)

    Schubert, E. F.

    2005-08-01

    Part I: 1. Introduction E. F. Schubert; Part II: 2. Electronic structure of delta-doped semiconductors C. R. Proetto; Part III: 3. Recent progress in delta-like confinement of impurities in GaAs K. H. Ploog; 4. Flow-rate modulation epitaxy (FME) of III-V semiconductors T. Makimoto and Y. Horikoshi; 5. Gas source molecular beam epitaxy (MBE) of delta-doped III-V semiconductors D. Ritter; 6. Solid phase epitaxy for delta-doping in silicon I. Eisele; 7. Low temperature MBE of silicon H.-J. Gossmann; Part IV: 8. Secondary ion mass spectrometry of delta-doped semiconductors H. S. Luftmann; 9. Capacitance-voltage profiling E. F. Schubert; 10. Redistribution of impurities in III-V semiconductors E. F. Schubert; 11. Dopant diffusion and segregation in delta-doped silicon films H.-J. Gossmann; 12. Characterisation of silicon and delta-doped structures in GaAs R. C. Newman; 13. The DX-center in silicon delta-doped GaAs and AlxGa1-xAs P. M. Koenraad; Part V: 14. Luminescence and ellipsometry spectroscopy H. Yao and E. F. Schubert; 15. Photoluminescence and Raman spectroscopy of single delta-doped III-V semiconductor heterostructures J. Wagner and D. Richards; 16. Electron transport in delta-doped quantum wells W. T. Masselink; 17. Electron mobility in delta-doped layers P. M. Koenraad; 18. Hot electrons in delta-doped GaAs M. Asche; 19. Ordered delta-doping R. L. Headrick, L. C. Feldman and B. E. Weir; Part IV: 20. Delta-doped channel III-V field effect transistors (FETs) W.-P. Hong; 21. Selectively doped heterostructure devices E. F. Schubert; 22. Silicon atomic layer doping FET K. Nakagawa and K. Yamaguchi; 23. Planar doped barrier devices R. J. Malik; 24. Silicon interband and intersubband photodetectors I. Eisele; 25. Doping superlattice devices E. F. Schubert.

  5. A global transcriptional analysis of Megalobrama amblycephala revealing the molecular determinants of diet-induced hepatic steatosis.

    PubMed

    Zhang, Dingdong; Lu, Kangle; Jiang, Guangzhen; Liu, Wenbin; Dong, Zaijie; Tian, Hongyan; Li, Xiangfei

    2015-10-10

    Blunt snout bream (Megalobrama amblycephala), a prevalent species in China's intensive polyculture systems, is highly susceptible to hepatic steatosis, resulting in considerable losses to the fish farming industry. Due to a lack of genomic resources, the molecular mechanisms of lipid metabolism in M. amblycephala are poorly understood. Here, a hepatic cDNA library was generated from equal amounts of mRNAs isolated from M. amblycephala fed normal-fat and high-fat diets. Sequencing of this library using the Illumina/Solexa platform produced approximately 51.87 million clean reads, which were assembled into 48,439 unigenes with an average length of 596 bp and an N50 value of 800 bp. These unigenes were searched against the nucleotide (NT), non-redundant (NR), Swiss-Prot, Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genome (KEGG) databases using the BLASTn or BLASTx algorithms (E-value ≤ 10(-5)). A total of 8602 unigenes and 22,155 unigenes were functionally classified into 25 COG categories and 259 KEGG pathways, respectively. Furthermore, 22,072 unigenes were grouped into 62 sub-categories belonging to three main Gene Ontology (GO) terms. Using a digital gene expression analysis and the M. amblycephala transcriptome as a reference, 477 genes (134 up-regulated and 343 down-regulated) were identified as differentially expressed in fish fed a high-fat diet versus a normal-fat diet. KEGG and GO functional enrichment analyses of the differentially expressed unigenes were performed and 12 candidate genes related to lipid metabolism were identified. This study provides a global survey of hepatic transcriptome profiles and identifies candidate genes that may be related to lipid metabolism in M. amblycephala. These findings will facilitate further investigations of the mechanisms underlying hepatic steatosis in M. amblycephala.

  6. Non-travel-associated hepatitis E in England and Wales: demographic, clinical, and molecular epidemiological characteristics.

    PubMed

    Ijaz, Samreen; Arnold, Eve; Banks, Malcolm; Bendall, Richard P; Cramp, Matthew E; Cunningham, Richard; Dalton, Harry R; Harrison, Tim J; Hill, Simon F; Macfarlane, Lorna; Meigh, Rolf E; Shafi, Shuja; Sheppard, Martin J; Smithson, Jacquie; Wilson, Melanie P; Teo, Chong-Gee

    2005-10-01

    Between 1996 and 2003, 186 cases of hepatitis E were serologically diagnosed. Of these, 17 (9%) were not associated with recent travel abroad. Patients were >55 years old (range, 56-82 years old) and tended to be male (76%). Two patients presented with fulminant hepatitis. A total of 129 (69%) cases were associated with recent travel to countries where hepatitis E virus (HEV) is hyperendemic. Compared with patients with travel-associated disease, patients with non-travel-associated disease were more likely to be older, living in coastal or estuarine areas, not of South Asian ethnicity, and infected by genotype 3 strains of HEV. The genotype 3 subgenomic nucleotide sequences were unique and closely related to those from British pigs. Patients infected by HEV indigenous to England and Wales tended to belong to a distinct demographic group, there were multiple sources of infection, and pigs might have been a viral reservoir.

  7. Serologic and molecular characteristics of hepatitis B virus among school children in East Java, Indonesia.

    PubMed

    Utsumi, Takako; Yano, Yoshihiko; Lusida, Maria Inge; Amin, Mochamad; Soetjipto; Hotta, Hak; Hayashi, Yoshitake

    2010-07-01

    Universal childhood hepatitis B vaccination was introduced in Indonesia in 1997; by 2008, coverage was estimated to be 78%. This study aimed to investigate the serologic status and virologic characteristics of hepatitis B virus (HBV) among the children in East Java. A total of 229 healthy children born during 1994-1999 were enrolled in this study. Overall, 3.1% were positive for hepatitis B surface antigen (HBsAg) and 23.6% were positive for antibody to HBsAg (anti-HBs). HBV DNA was detected in 5 of 222 HBsAg-negative carriers, which were suggested to be cases of occult HBV infection. A single amino substitution (T126I) in the S region was frequently found. HBV infection remains endemic, and the prevalence of anti-HBs remains insufficient among children in East Java, Indonesia.

  8. Which molecular features affect the intrinsic hepatic clearance rate of ionizable organic chemicals in fish?

    EPA Science Inventory

    Greater knowledge of biotransformation rates for ionizable organic compounds (IOCs) in fish is required to properly assess the bioaccumulation potential of many environmentally relevant contaminants. In this study we measured in vitro hepatic clearance rates for 50 IOCs using a p...

  9. Trigonelline attenuates hepatic complications and molecular alterations in high-fat high-fructose diet-induced insulin resistance in rats.

    PubMed

    Afifi, Nehal A; Ramadan, Amer; Erian, Emad Y; Saleh, Dalia O; Sedik, Ahmed A; Badawi, Manal; El Hotaby, Walid

    2017-04-01

    The present study aimed to evaluate the effect of trigonelline (TRG) on the hepatic complications associated with high-fat high-fructose (HFHF) diet-induced insulin resistance (IR) in rats. IR was induced by giving a saturated fat diet and 10% fructose in drinking water to rats for 8 weeks. Insulin-resistant rats were orally treated with TRG (50 and 100 mg/kg), sitagliptin (SIT; 5 mg/kg), or a combination of TRG (50 mg/kg) and SIT (5 mg/kg) for 14 days. Liver homogenates were used for assessment of hepatic lipids, oxidative stress biomarkers, and inflammatory cytokines. Histopathological and DNA cytometry examinations were carried out for hepatic and pancreatic tissues. Hepatic tissues were examined using Fourier-transform infrared spectroscopy for assessment of any molecular changes. Results of the present study revealed that oral treatment of insulin-resistant rats with TRG or TRG in combination with SIT significantly decreased homeostatic model assessment of IR, hepatic lipids, oxidative stress biomarkers, and the inflammatory cytokines. TRG or TRG in combination with SIT ameliorated the histopathological, DNA cytometry, and molecular alterations induced by a HFHF diet. Finally, it can be concluded that TRG has beneficial effects on the hepatic complications associated with IR due to its hypoglycemic effect and antioxidant potential.

  10. Molecular temporal bone pathology: III. Genotyping of the deltaF508 deletion in the DNA of patients with cystic fibrosis.

    PubMed

    Wackym, P A; Kerner, M M; Grody, W W

    1998-08-01

    Genomic DNA from a single celloidin-embedded archival temporal bone section was used to identify a specific genetic mutation. The polymerase chain reaction was used to amplify and detect the deltaF508 deletion, a common molecular genetic defect in cystic fibrosis. This mutation, present in more than 70% of white patients and carriers with cystic fibrosis, results in the deletion of codon 508, which specifies the amino acid phenylalanine of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. When this technique was applied to archival specimens from four patients with cystic fibrosis, all expressed the carrier state of this defective gene. These data demonstrate the feasibility of identifying genetic mutations in archival temporal bone specimens.

  11. Prevalence of hepatitis viruses in patients with acute hepatitis and characterization of the detected genotype 4 hepatitis E virus sequences in Mongolia.

    PubMed

    Tsatsralt-Od, Bira; Baasanjav, Nachin; Nyamkhuu, Dulmaa; Ohnishi, Hiroshi; Takahashi, Masaharu; Okamoto, Hiroaki

    2016-02-01

    Hepatitis E is considered to be a worldwide public health problem. Although the prevalence of hepatitis E virus (HEV) antibodies in healthy individuals is noted to be 11%, no patients with acute hepatitis E have previously been identified in Mongolia. Three hundred two consecutive patients (183 males and 119 females; median age of 22.0 [Interquartile range: 18.3-25.0] years) who were clinically diagnosed with sporadic acute hepatitis during 2012-2013 in Ulaanbaatar, Mongolia, were studied. By serological and/or molecular approaches, 77 (25.5%), 93 (30.8%), 19 (6.3%), 48 (15.9%), and 12 (4.0%) of the patients were diagnosed with acute hepatitis of types A, B, C, D (superinfection of hepatitis delta virus on a background of chronic hepatitis B virus infection) and E, respectively, while the cause of hepatitis was unknown in the remaining 53 patients (17.5%). The 12 hepatitis E patients had no history of travel abroad in the 3 months before the onset of disease, and lived separately in fixed or movable houses with water supplied via pipe, tank or well, denying transmission from a common water supply. The 12 HEV isolates obtained from the patients showed high nucleotide identities of 99.7-100%, and a representative HEV isolate, MNE13-227, was closest to the Chinese isolates of genotype 4, with the highest identity of 97.3% in the 304-nt ORF2 sequence and 92.1% over the entire genome. The present study revealed the occurrence of autochthonous acute hepatitis E in Mongolia, caused by a monophyletic genotype 4 HEV strain.

  12. Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC): molecular mechanisms and novel paradigms.

    PubMed

    Brechot, C; Kremsdorf, D; Soussan, P; Pineau, P; Dejean, A; Paterlini-Brechot, P; Tiollais, P

    2010-08-01

    Chronic hepatitis B (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Most HCCs complicate the evolution of an active or inactive cirrhosis. However, some tumors occur on livers with minimal histological changes; the prevalence of such cases varies from one geographical region to the other, being much higher in the Southern half of Africa (around 40% of HCCs) than in Asia, America and Europe, where at least 90% of HCCs are associated in the cirrhosis. This heterogeneity is probably a reflection of different environmental and genetic factors. This review will summarise the current knowledge on the mechanisms involved in HBV-related liver carcinogenesis. It will show in particular how viruses can be viewed as tools to discover and dissect new cellular pathways involved in cancer development and emphasize the potential synergistic effects between HBV and hepatitis C virus (HCV), as well as between viral infections and other environmental factors, such as alcohol.

  13. Incidence and Molecular Characterization of Hepatitis E Virus from Swine in Eastern Cape, South Africa

    PubMed Central

    Chuks Iweriebor, Benson; Nwodo, U. U.; Obi, Larry Chikwelu; Okoh, Anthony Ifeanyi

    2017-01-01

    Hepatitis E virus-mediated infection is a serious public health concern in economically developing nations of the world. Globally, four major genotypes of HEV have been documented. Hepatitis E has been suggested to be zoonotic owing to the increase of evidence through various studies. Thus far, this paper reports on prevalence of hepatitis E virus among swine herd in selected communal and commercial farms in the Eastern Cape Province of South Africa. A total of 160 faecal samples were collected from swine herds in Amathole and Chris Hani District Municipalities of Eastern Cape Province for the presence of HEV. Of the 160 faecal samples screened, only seven were positive (4.4%) for HEV. The nucleotide sequences analyses revealed the isolates as sharing 82% to 99% identities with other strains (KX896664, KX896665, KX896666, KX896667, KX896668, KX896669, and KX896670) from different regions of the world. We conclude that HEV is present among swine in the Eastern Cape Province, albeit in low incidence, and this does have public health implications. There is a need for maintenance of high hygienic standards in order to prevent human infections through swine faecal materials and appropriate cooking of pork is highly advised. PMID:28191016

  14. Molecular diagnostics in the management of chronic hepatitis C: key considerations in the era of new antiviral therapies

    PubMed Central

    2014-01-01

    Molecular tests that detect and/or quantify HCV RNA are important in the diagnosis and management of patients with chronic hepatitis C (CHC) undergoing anti-viral therapy. The primary goal of anti-HCV therapy is to achieve a sustained virologic response (SVR) defined as "undetectable" Hepatitis C Virus (HCV) RNA in the serum or plasma at 12 to 24 weeks following the end of treatment. HCV RNA viral load (VL) monitoring is used to guide treatment duration where decisions can be made on-therapy and to determine whether or not to stop therapy. In addition, clinicians determine treatment regimen and duration based on the HCV genotype (1-6) as well as the kinetics of HCV RNA levels. As direct acting antivirals (DAA) have revolutionized hepatitis C treatment, they have also lead to new HCV RNA VL result interpretations. Further, the clinical decisions were different for pegylated-interferon/ribavirin (PEGα/RBV)+ boceprevir or telaprevir-containing regimens approved in 2011 (e.g. one requiring an additional 4 week "lead-in" with PEGα/RBV), each having different HCV RNA values for futility rules, created complexity in clinical decisions. The future pegylated-interferon free DAA- regimens promise significantly improved cure rates along with fixed durations and simpler treatment rules. The intent of this article is to discuss the role of HCV RNA real-time PCR tests used in the management of CHC patients in the past and how this is likely to change in the era of interferon free DAA regimens. PMID:25236936

  15. Hepatitis B

    MedlinePlus

    ... Home » Hepatitis B » Hepatitis B Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis B Entire Lesson for Veterans and the Public ...

  16. Molecular epidemiology of human hepatitis A virus defined by an antigen-capture polymerase chain reaction method.

    PubMed Central

    Jansen, R W; Siegl, G; Lemon, S M

    1990-01-01

    We describe an immunoaffinity-linked nucleic acid amplification system (antigen-capture/polymerase chain reaction, or AC/PCR) for detection of viruses in clinical specimens and its application to the study of the molecular epidemiology of a picornavirus, hepatitis A virus (HAV). Immunoaffinity capture of virus, synthesis of viral cDNA, and amplification of cDNA by a polymerase chain reaction (PCR) were carried out sequentially in a single reaction vessel. This approach simplified sample preparation and enhanced the specificity of conventional PCR. AC/PCR detected less than one cell culture infectious unit of virus in 80 microliters of sample. Sequencing of AC/PCR reaction products from 34 virus strains demonstrated remarkable conservation at the nucleotide level among most strains but revealed hitherto unsuspected genetic diversity among human isolates. Epidemiologically related strains were identical or closely related in sequence. Virus strains recovered from epidemics of hepatitis A in the United States and Germany were identical in sequence, providing evidence for a previously unrecognized epidemiologic link between these outbreaks. Images PMID:2158093

  17. Albumin dialysis with molecular adsorbent recirculating system (MARS) for the treatment of hepatic encephalopathy in liver failure.

    PubMed

    Kobashi-Margáin, Ramón A; Gavilanes-Espinar, Juan G; Gutiérrez-Grobe, Ylse; Gutiérrez-Jiménez, Angel A; Chávez-Tapia, Norberto; Ponciano-Rodríguez, Guadalupe; Uribe, Misael; Méndez Sánchez, Nahum

    2011-06-01

    Acute, acute-on-chronic and chronic liver diseases are major health issues worldwide, and most cases end with the need for liver transplantation. Up to 90% of the patients die waiting for an organ to be transplanted. Hepatic encephalopathy is a common neuropsychiatric syndrome that usually accompanies liver failure and impacts greatly on the quality of life. The molecular adsorbent recirculating system (MARS) is a recently developed form of artificial liver support that functions on a base of albumin dialysis. It facilitates the dialysis of albumin-bound and water-soluble toxins, allowing the patient to survive and even improving some clinical features of liver failure. The following manuscript reviews the technical features of MARS operation and some of the clinical trials that analyze the efficacy of the system in the therapy of liver diseases.

  18. Molecular mimicry between Fc receptor and S peplomer protein of mouse hepatitis virus, bovine corona virus, and transmissible gastroenteritis virus.

    PubMed

    Oleszak, E L; Kuzmak, J; Hogue, B; Parr, R; Collisson, E W; Rodkey, L S; Leibowitz, J L

    1995-02-01

    We have previously demonstrated molecular mimicry between the S peplomer protein of mouse hepatitis virus (MHV) and Fc gamma R (Fc gamma R). A monoclonal antibody (MAb) to mouse Fc gamma R (2.4G2 anti-Fc gamma R MAb), purified rabbit immunoglobulin, but not their F(ab')2 fragments, as well as mouse and rat IgG, immunoprecipitated (1) recombinant S peplomer protein expressed by a vaccinia virus recombinant in human, rabbit, and mouse cells, and (2) natural S peplomer protein from cells infected with several strains of MHV and MHV escaped mutants. We report here results of studies documenting molecular mimicry between Fc gamma R and S peplomer protein of viruses representing three distinct antigenic subgroups of the Coronaviridae. We have shown a molecular mimicry between the S peplomer protein of bovine corona virus (BCV) and Fc gamma R. The 2.4G2 anti-Fc gamma R MAb, rabbit IgG, but not its F(ab')2 fragments, as well as homologous bovine serum, free of anti-BCV antibodies, immunoprecipitated S peplomer protein of BCV (Mebus strain). In contrast, we did not find molecular mimicry between S peplomer protein of human corona virus (HCV-OC43) and Fc gamma R. Although the OC43 virus belongs to the same antigenic group as MHV and BCV, MAb specific for human Fc gamma RI or Fc gamma RII and purified human IgG1, IgG2, and IgG3 myeloma proteins did not immunoprecipitate the S peplomer protein from HCV-OC43-infected RD cells. In addition, we did demonstrate molecular mimicry between the S peplomer protein of porcine transmissible gastroenteritis virus (TGEV) and Fc gamma R. TGEV belongs to the second antigenic subgroup of coronaviridae.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis): A model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans

    PubMed Central

    2012-01-01

    Background Hepatitis B virus (HBV) infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia) is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. Whether tree shrews could be chronically infected with HBV in vivo has been controversial for decades. Most published research has been reported on adult tree shrews, and only small numbers of HBV infected newborn tree shrews had been observed over short time periods. We investigated susceptibility of newborn tree shrews to experimental HBV infection as well as viral clearance over a protracted time period. Results Forty-six newborn tree shrews were inoculated with the sera from HBV-infected patients or tree shrews. Serum and liver samples of the inoculated animals were periodically collected and analyzed using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Southern blot, and immunohistochemistry. Six tree shrews were confirmed and four were suspected as chronically HBV-infected for more than 48 (up to 228) weeks after inoculation, including three that had been inoculated with serum from a confirmed HBV-infected tree shrew. Conclusions Outbred neonatal tree shrews can be long-term chronically infected with HBV at a frequency comparable to humans. The model resembles human disease where also a smaller proportion of infected individuals develop chronic HBV related disease. This model might enable genetic and immunologic investigations which would allow determination of underlying molecular causes favoring susceptibility for chronic HBV infection and disease establishment vs. viral clearance. PMID:22913805

  20. Molecular Basis of the Behavior of Hepatitis A Virus Exposed to High Hydrostatic Pressure

    PubMed Central

    D'Andrea, Lucía; Pérez-Rodríguez, Francisco J.; Costafreda, M. Isabel; Beguiristain, Nerea; Fuentes, Cristina; Aymerich, Teresa; Guix, Susana; Bosch, Albert

    2014-01-01

    Food-borne hepatitis A outbreaks may be prevented by subjecting foods at risk of virus contamination to moderate treatments of high hydrostatic pressure (HHP). A pretreatment promoting hepatitis A virus (HAV) capsid-folding changes enhances the virucidal effect of HHP, indicating that its efficacy depends on capsid conformation. HAV populations enriched in immature capsids (125S provirions) are more resistant to HHP, suggesting that mature capsids (150S virions) are more susceptible to this treatment. In addition, the monoclonal antibody (MAb) K24F2 epitope contained in the immunodominant site is a key factor for the resistance to HHP. Changes in capsid folding inducing a loss of recognition by MAb K24F2 render more susceptible conformations independently of the origin of such changes. Accordingly, codon usage-associated folding changes and changes stimulated by pH-dependent breathings, provided they confer a loss of recognition by MAb K24F2, induce a higher susceptibility to HHP. In conclusion, the resistance of HAV to HHP treatments may be explained by a low proportion of 150S particles combined with a good accessibility of the epitope contained in the immunodominant site close to the 5-fold axis. PMID:25107980

  1. Epidemiology and molecular characterisation of duck hepatitis A virus from different duck breeds in Egypt.

    PubMed

    Erfan, Ahmed M; Selim, Abdullah A; Moursi, Mohamed K; Nasef, Soad A; Abdelwhab, E M

    2015-06-12

    Duck hepatitis virus (DHV) is an acute highly contagious disease of ducklings caused by three distinct serotypes of duck hepatitis A virus (DHAV), a member of the RNA family Picornaviridae, where serotype 1 is the most widespread serotype worldwide. To date, little if any is known about the prevalence and genetic characterisation of DHAV outside Asia. The current study describes surveillance on DHV in 46 commercial duck farms in Egypt with a history of high mortality in young ducklings from 3 to 15 day-old from 2012 to 2014. Clinical samples were examined by generic RT-PCR assays followed by partial sequence analysis of the 5'UTR, VP1 and 3D genes of the vaccine strain and 15 field viruses. The overall positive rate was 37% (n=17/46). All duck breeds (Pekin, Muscovy, Mallard and Green Winged) were susceptible to the disease with mortality ranged from 15% to 96.7%. Sequence and phylogenetic analyses indicated that the Egyptian strains cluster in the DHAV serotype 1 with Asian viruses and distinguishable from the vaccine strains. So far, this is the first report on the genetic characterisation of DHAV in Egypt. This study may be useful to better understand the epidemiology and evolution of DHAV.

  2. Serologic and Molecular Survey of Hepatitis E Virus in German Deer Populations.

    PubMed

    Neumann, Stephan; Hackl, Sybille S; Piepenschneider, Meike; Vina-Rodriguez, Ariel; Dremsek, Paul; Ulrich, Rainer G; Groschup, Martin H; Eiden, Martin

    2016-01-01

    Hepatitis E virus (HEV) is a human pathogen that is primarily transmitted by the fecal-oral route and causes a usually self-limiting acute viral hepatitis. The virus is endemic in developing countries of Africa, Asia, and Latin America and is responsible for sporadic cases in industrialized countries. In western Europe, an increasing number of autochthonous cases have been associated with zoonotic transmissions of HEV from domestic and wild animals. In Germany, animal reservoirs for HEV have been mainly assigned to domestic pigs and wild boars. To investigate the potential role of deer as a reservoir of HEV, we surveyed HEV-specific antibodies and RNA in deer samples from geographic regions in Germany. We sampled red deer (Cervus elaphus) and roe deer (Capreolus capreolus) during active surveillance in three forest districts in northern Hesse and southern Lower Saxony during 2011-12 and 2012-13, respectively. Additionally, archived samples of red, roe, and fallow deer (Dama dama), collected in 2000-01 in German national parks, were included in the study. Antibody prevalence ranged from 2-3.3% in red deer to 5.4-6.8% in roe deer. Viral RNA was detected in red deer and fallow deer at prevalences of 2.0-6.6% and 4.3%, respectively. The investigation confirmed the presence of HEV infections in three deer species in Germany. Red, roe, and fallow deer should be further monitored to assess their role as hosts and potential reservoirs of HEV in Germany.

  3. Molecular characterization of subgenotype A1 (subgroup Aa) of hepatitis B virus.

    PubMed

    Kramvis, Anna; Kew, Michael C

    2007-07-01

    Subgenotypes of hepatitis B virus (HBV) were first recognized after a unique segment of genotype A was identified when sequencing the preS2/S region of southern African HBV isolates. Originally named subgroup A', subsequently called subgroup Aa (for Africa) or subgenotype A1, this subgenotype is found in South Africa, Malawi, Uganda, Tanzania, Somalia, Yemen, India, Nepal, the Philippines and Brazil. The relatively higher mean nucleotide divergence of subgenotype A1 suggests that it has been endemic and has a long evolutionary history in the populations where it prevails. Distinctive sequence characteristics could account for the high hepatitis B e-antigen (HBeAg) negativity and low HBV DNA levels in carriers of this subgenotype. Substitutions or mutations can reduce HBeAg expression at three levels: (i) 1762T1764A atthe transcriptional level; (ii) substitutions at nt 1809-1812 at the translational level; and (iii) 1862T at the post-translational level. Co-existence of 1762T1764A and nt 1809-1812 mutations reduces HBeAg expression in an additive manner. In addition, subgenotype A1 has unique sequence alterations in the transcriptional regulatory elements and the polymerase coding region. The distinct sequence characteristics of subgenotype A1 may contribute to the 4.5-fold increased risk of heptocellular carcinoma in HBV carriers infected with genotype A, which is entirely attributable to subgenotype A1.

  4. Hepatitis B and concomitant hepatic steatosis

    PubMed Central

    Lim, Chong Teik

    2017-01-01

    Hepatic steatosis is becoming more common in Asia with prevalence becoming as common as Western countries. Concomitant Hepatitis B and hepatic steatosis is increasingly encountered in clinical practice. The interaction between the two concomitant conditions at both molecular level and clinical outcome remains to be explored. The present review is aimed at summarizing the existing literature on the complex interaction of the two-concomitant disease. PMID:28251117

  5. Predation on larval suckers in the Williamson River Delta revealed by molecular genetic assays—A pilot study

    USGS Publications Warehouse

    Hereford, Danielle M.; Ostberg, Carl O.; Burdick, Summer M.

    2016-06-13

    Predation of endangered Lost River suckers (Deltistes luxatus) and shortnose suckers (Chasmistes brevirostris) during larval egress to Upper Klamath Lake from the Williamson River is poorly understood but may be an important factor limiting recruitment into adult spawning populations. Native and non-native piscivores are abundant in nursery wetland habitat, but larval predation has not been directly studied for all species. Larvae lack hard body structures and digest rapidly in predator digestive systems. Therefore, traditional visual methods for diet analysis may fail to identify the extent of predation on larvae. The goals of this study were to (1) use quantitative polymerase chain reaction (qPCR) and single nucleotide polymorphism (SNP) assays developed for Lost River and shortnose suckers to assay predator stomach contents for sucker DNA, and (2) to assess our ability to use this technique to study predation. Predators were captured opportunistically during larval sucker egress. Concurrent feeding trials indicate that most predators—yellow perch (Perca flaverscens), fathead minnow (Pimephales promelas), blue chub (Gila coerulea), Klamath tui chub (Siphatales bicolor bicolor), Klamath Lake sculpin (Cottus princeps), slender sculpin (Cottus tenuis)—preyed on sucker larvae in the laboratory. However, sucker DNA was not detected in fathead minnow stomachs. Of the stomachs screened from fish captured in the Williamson River Delta, 15.6 percent of yellow perch contained sucker DNA. This study has demonstrated that the application of qPCR and SNP assays is effective for studying predation on larval suckers. We suggest that techniques associated with dissection or detection of sucker DNA from fathead minnow stomachs need improvement.

  6. Neferine inhibits cultured hepatic stellate cell activation and facilitates apoptosis: A possible molecular mechanism.

    PubMed

    Ding, Hui; Shi, Jinghong; Wang, Ying; Guo, Jia; Zhao, Juhui; Dong, Lei

    2011-01-10

    Neferine is a major alkaloid component of "Lian Zi Xin", embryos of the seeds of Nelumbo nucifera Gaertner, Nymphaeaceae. Previous studies have shown that neferine has an inhibitory effect on pulmonary fibrosis through its anti-inflammatory and anti-oxidative activities and inhibition of cytokines and NF-κB. However, it is unknown whether neferine also has an inhibitory effect on liver fibrosis through inhibition of TGF-β1 and collagen I and facilitation of apoptosis of hepatic stellate cells. This study examined the effects of neferine on cultured hepatic stellate (HSC-T6) cells and explored its possible action mechanisms by means of MTT assay, enzyme-linked immunosorbent assay, flow-cytometric annexin V-PI assay and Hoechst 33258 staining, as well as real-time PCR and western blotting. The results showed that neferine administration (2, 4, 6, 8 and 10μmol/l) significantly decreased the TGF-β1 and collagen I produced in HSC-T6 cells, and increased the HSC-T6 cell apoptosis in a dose-dependent manner. Neferine treatment for 48h at concentrations of 6 and 10μmol/l significantly increased Bax and caspase 3 mRNAs and proteins, and reduced Bcl2 and alpha-smooth muscle actin (α-SMA) mRNAs and proteins. Our data indicate that neferine efficiently inhibits cultured HSC-T6 cell activation and induces apoptosis by increasing Bax and caspase 3 expression via the mitochondrial pathway.

  7. Molecular Differences in Hepatic Metabolism between AA Broiler and Big Bone Chickens: A Proteomic Study

    PubMed Central

    Liu, Guohua; Yue, Ying; Li, Jianke; Zhang, Shu; Cai, Huiyi; Yang, Aijun; Chen, Zhimin

    2016-01-01

    Identifying the metabolic differences in the livers of modern broilers and local chicken breeds is important for understanding their biological characteristics, and many proteomic changes in their livers are not well characterized. We therefore analyzed the hepatic protein profiles of a commercial breed, Arbor Acres (AA) broilers, and a local dual purpose breed, Big Bone chickens, using two-dimensional electrophoresis combined with liquid chromatography-chip/electrospray ionization-quadruple time-of-flight/mass spectrometry (LC-MS/MS). A total of 145 proteins were identified as having differential abundance in the two breeds at three growth stages. Among them, 49, 63 and 54 belonged to 2, 4, and 6 weeks of age, respectively. The higher abundance proteins in AA broilers were related to the energy production pathways suggesting enhanced energy metabolism and lipid biosynthesis. In contrast, the higher abundance proteins in Big Bone chickens showed enhanced lipid degradation, resulting in a reduction in the abdominal fat percentage. Along with the decrease in fat deposition, flavor substance synthesis in the meat of the Big Bone chickens may be improved by enhanced abundance of proteins involved in glycine metabolism. In addition, the identified proteins in nucleotide metabolism, antioxidants, cell structure, protein folding and transporters may be critically important for immune defense, gene transcription and other biological processes in the two breeds. These results indicate that selection pressure may have shaped the two lines differently resulting in different hepatic metabolic capacities and extensive metabolic differences in the liver. The results from this study may help provide the theoretical basis for chicken breeding. PMID:27760160

  8. Molecular virology of hepatitis B virus, sub-genotype C4 in northern Australian Indigenous populations.

    PubMed

    Littlejohn, M; Davies, J; Yuen, L; Edwards, R; Sozzi, T; Jackson, K; Cowie, B; Tong, S; Davis, J; Locarnini, S

    2014-04-01

    Indigenous Australians experience a significant health burden from chronic hepatitis B infection; however, the strain of hepatitis B virus (HBV) found among Indigenous Australians has not been well characterized. Blood samples were collected from 65 Indigenous Australians with chronic HBV infection from across the Top End of Australia's Northern Territory. Phylogenetic analysis of HBV from these samples revealed that 100% of the isolates were genotype C, sub-genotype C4, expressing the serotype ayw3. This strain is a divergent group within the HBV/C genotype, and has only been described in Indigenous Australians. Evidence of recombination was suggested by discordant phylogenetic clustering of the C4 sequences when comparing the full genome to the surface region and confirmed by recombination analysis which showed the surface gene region to be most closely related to genotype J, while the remaining regions of the genome were most similar to genotype C sequences. Mutational analysis revealed the presence of multiple mutations that have been linked with more rapid liver disease progression and an increased risk of hepatocellular carcinoma. These mutations were detected in the majority of sequences examined. Variants associated with vaccine failure were detected as the predominant viral quasi-species in 3/35 samples. In summary, the HBV C4 variant found in this population has a high potential to cause advanced liver disease and to escape vaccination programs. Further in vitro functional and natural history studies are warranted in order to determine the clinical and public health consequences of infection with the HBV C4 variant in these communities.

  9. Molecular Differences in Hepatic Metabolism between AA Broiler and Big Bone Chickens: A Proteomic Study.

    PubMed

    Zheng, Aijuan; Chang, Wenhuan; Liu, Guohua; Yue, Ying; Li, Jianke; Zhang, Shu; Cai, Huiyi; Yang, Aijun; Chen, Zhimin

    2016-01-01

    Identifying the metabolic differences in the livers of modern broilers and local chicken breeds is important for understanding their biological characteristics, and many proteomic changes in their livers are not well characterized. We therefore analyzed the hepatic protein profiles of a commercial breed, Arbor Acres (AA) broilers, and a local dual purpose breed, Big Bone chickens, using two-dimensional electrophoresis combined with liquid chromatography-chip/electrospray ionization-quadruple time-of-flight/mass spectrometry (LC-MS/MS). A total of 145 proteins were identified as having differential abundance in the two breeds at three growth stages. Among them, 49, 63 and 54 belonged to 2, 4, and 6 weeks of age, respectively. The higher abundance proteins in AA broilers were related to the energy production pathways suggesting enhanced energy metabolism and lipid biosynthesis. In contrast, the higher abundance proteins in Big Bone chickens showed enhanced lipid degradation, resulting in a reduction in the abdominal fat percentage. Along with the decrease in fat deposition, flavor substance synthesis in the meat of the Big Bone chickens may be improved by enhanced abundance of proteins involved in glycine metabolism. In addition, the identified proteins in nucleotide metabolism, antioxidants, cell structure, protein folding and transporters may be critically important for immune defense, gene transcription and other biological processes in the two breeds. These results indicate that selection pressure may have shaped the two lines differently resulting in different hepatic metabolic capacities and extensive metabolic differences in the liver. The results from this study may help provide the theoretical basis for chicken breeding.

  10. Molecular characterization, distribution, and dynamics of hepatitis C virus genotypes in blood donors in Colombia.

    PubMed

    Mora, Mónica Viviana Alvarado; Romano, Camila Malta; Gomes-Gouvêa, Michele Soares; Gutiérrez, Maria Fernanda; Carrilho, Flair José; Pinho, João Renato Rebello

    2010-11-01

    Hepatitis C virus (HCV) is a frequent cause of acute and chronic hepatitis and a leading cause for cirrhosis of the liver and hepatocellular carcinoma. HCV is classified in six major genotypes and more than 70 subtypes. In Colombian blood banks, serum samples were tested for anti-HCV antibodies using a third-generation ELISA. The aim of this study was to characterize the viral sequences in plasma of 184 volunteer blood donors who attended the "Banco Nacional de Sangre de la Cruz Roja Colombiana," Bogotá, Colombia. Three different HCV genomic regions were amplified by nested PCR. The first of these was a segment of 180 bp of the 5'UTR region to confirm the previous diagnosis by ELISA. From those that were positive to the 5'UTR region, two further segments were amplified for genotyping and subtyping by phylogenetic analysis: a segment of 380 bp from the NS5B region; and a segment of 391 bp from the E1 region. The distribution of HCV subtypes was: 1b (82.8%), 1a (5.7%), 2a (5.7%), 2b (2.8%), and 3a (2.8%). By applying Bayesian Markov chain Monte Carlo simulation, it was estimated that HCV-1b was introduced into Bogotá around 1950. Also, this subtype spread at an exponential rate between about 1970 to about 1990, after which transmission of HCV was reduced by anti-HCV testing of this population. Among Colombian blood donors, HCV genotype 1b is the most frequent genotype, especially in large urban conglomerates such as Bogotá, as is the case in other South American countries.

  11. Molecular characterisation of fowl adenovirus type 7 isolated from poultry associated with inclusion body hepatitis in Poland.

    PubMed

    Niczyporuk, Jowita Samanta

    2017-02-03

    The fowl adenovirus field strain FAdV-JSN-5/10j (GenBank accession number KP879219) was isolated from the intestine of a 7-week-old chicken diagnosed with inclusion body hepatitis and simultaneously with Marek's disease, and for that reason, it was chosen for molecular study. It was identified as fowl adenovirus genotype 7 (species Fowl aviadenovirus E) based on nucleotide sequence analysis of the loop L1 region of the hexon gene. Nucleotide sequence alignment of this strain, FAdV-7 reference strains B-3A ATCC VR-832 (AF339922) and YR36 (AF508955), and eight additional FAdV-7 field strains confirmed its classification as FAdV-JS-5/10j and showed that these viruses are very similar to each other. Additionally, we described mutations and their influence on the amino acid sequence, nucleotide composition, and relative synonymous codon usage. Immunofluorescence of cell cultures infected with 10(4.5) TCID 50 per 0.1-ml dose of the FAdV-JSN-5/10j strain demonstrated the presence of a cytopathic effect. Infection of fowl with adenoviruses raises concerns for poultry production, and thus, the efficient detection of adenovirus infection is crucial. This is the first attempt to describe the molecular characteristics of FadV-7 strains isolated in Poland.

  12. The Prevalence and Risk Factors of Hepatitis Delta Virus in HIV/HBV Co-Infected Patients in Shiraz, Iran, 2012

    PubMed Central

    Motamedifar, Mohammad; Taheri, Mohammad; Lankarani, Kamran Bagheri; Gholami, Mina; Lari, Mahmood Amini; Faramarzi, Hossein; Sarvari, Jamal

    2015-01-01

    Evidence has shown that liver disease caused by hepatitis viruses can be more aggressive and severe in HIV infected subjects. Therefore, the present cross-sectional study aimed to evaluate the seroprevalence of HDV infection among HIV/HBV co-infected clients in Shiraz, southwest Iran. In this study, 178 patients co-infected with HBV and HIV individuals were enrolled. The diagnosis of HIV infection was documented based on serological assays. The demographic and complementary data were collected by a questionnaire. HBsAg and HDV Ab were detected by commercial quantitative enzyme linked immunosorbent assay kits according to the manufacturer’s instructions. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also measured. The mean age of the participants was 37.4±7.4 years (range 22-63). 175 (98.4 %) patients were male and 3 (1.6 %) were female. Among 178 patients co-infected with HIV/HBV, 35 cases (19.7%, 95% CI: 14%-25%) were anti-HDV‏ positive and 143 (80.3%) were negative for anti-HDV. HDV exposure in HIV/HBV co-infected patients was associated with blood transfusion (P=0.002, OR: 14.3) and prison history (P=0.01, OR: 2.31) but not with age, marital status, unsafe sex contact, and injection drug abuse. Our data showed a relatively high prevalence of HDV infection in HIV infected population in Shiraz, Iran. The high frequency of HDV Ab in patients with blood transfusion and prison history reveals that HDV transmission occurs more frequently in the parental route than sexual contacts; therefore, blood screening for HDV diagnosis in the high-risk group is recommended. PMID:26379352

  13. Hepatitis A

    MedlinePlus

    Hepatitis A Hepatitis A Hepatitis A is a contagious viral infection that can easily affect children and adults. It is one of the most common types of hepatitis virus. Often when you hear about hepatitis A ...

  14. The Molecular Basis of Drug Resistance against Hepatitis C Virus NS3/4A Protease Inhibitors

    PubMed Central

    Romano, Keith P.; Ali, Akbar; Aydin, Cihan; Soumana, Djade; Özen, Ayşegül; Deveau, Laura M.; Silver, Casey; Cao, Hong; Newton, Alicia; Petropoulos, Christos J.; Huang, Wei; Schiffer, Celia A.

    2012-01-01

    Hepatitis C virus (HCV) infects over 170 million people worldwide and is the leading cause of chronic liver diseases, including cirrhosis, liver failure, and liver cancer. Available antiviral therapies cause severe side effects and are effective only for a subset of patients, though treatment outcomes have recently been improved by the combination therapy now including boceprevir and telaprevir, which inhibit the viral NS3/4A protease. Despite extensive efforts to develop more potent next-generation protease inhibitors, however, the long-term efficacy of this drug class is challenged by the rapid emergence of resistance. Single-site mutations at protease residues R155, A156 and D168 confer resistance to nearly all inhibitors in clinical development. Thus, developing the next-generation of drugs that retain activity against a broader spectrum of resistant viral variants requires a comprehensive understanding of the molecular basis of drug resistance. In this study, 16 high-resolution crystal structures of four representative protease inhibitors – telaprevir, danoprevir, vaniprevir and MK-5172 – in complex with the wild-type protease and three major drug-resistant variants R155K, A156T and D168A, reveal unique molecular underpinnings of resistance to each drug. The drugs exhibit differential susceptibilities to these protease variants in both enzymatic and antiviral assays. Telaprevir, danoprevir and vaniprevir interact directly with sites that confer resistance upon mutation, while MK-5172 interacts in a unique conformation with the catalytic triad. This novel mode of MK-5172 binding explains its retained potency against two multi-drug-resistant variants, R155K and D168A. These findings define the molecular basis of HCV N3/4A protease inhibitor resistance and provide potential strategies for designing robust therapies against this rapidly evolving virus. PMID:22910833

  15. Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease.

    PubMed

    Cheng, Jeffrey B; Jacquemin, Emmanuel; Gerhardt, Marie; Nazer, Hisham; Cresteil, Danièle; Heubi, James E; Setchell, Kenneth D R; Russell, David W

    2003-04-01

    The 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase (C(27) 3beta-HSD) is a membrane-bound enzyme of the endoplasmic reticulum that catalyzes an early step in the synthesis of bile acids from cholesterol. Subjects with autosomal recessive mutations in the encoding gene, HSD3B7, on chromosome 16p11.2-12 fail to synthesize bile acids and develop a form of progressive liver disease characterized by cholestatic jaundice and malabsorption of lipids and lipid-soluble vitamins from the gastrointestinal tract. The gene encoding the human C(27) 3beta-HSD enzyme was isolated previously, and a 2-bp deletion in exon 6 of HSD3B7 was identified in a well characterized subject with this disorder. Here, we report a molecular analysis of 15 additional patients from 13 kindreds with C(27) 3beta-HSD deficiency. Twelve different mutations were identified in the HSD3B7 gene on chromosome 16p11.2-12. Ten mutations were studied in detail and shown to cause complete loss of enzyme activity and, in two cases, alterations in the size or amount of the transcribed mRNA. Mutations were inherited in homozygous form in 13 subjects from 10 families and compound heterozygous form in four subjects from three families. We conclude that a diverse spectrum of mutations in the HSD3B7 gene underlies this rare form of neonatal cholestasis.

  16. Molecular characterization of antibiotic resistance in Pseudomonas and Aeromonas isolates from catfish of the Mekong Delta, Vietnam.

    PubMed

    Nguyen, Hoang Nam Kha; Van, Thi Thu Hao; Nguyen, Huu Thinh; Smooker, Peter M; Shimeta, Jeff; Coloe, Peter J

    2014-07-16

    A collection of 116 motile Pseudomonas spp. and 92 Aeromonas spp. isolated from 15 Vietnamese intensive catfish farms was analyzed to examine the molecular antibiotic resistance characteristics and the transferability of resistance markers within and between species. High levels of resistance to ampicillin, trimethoprim/sulfamethoxazole, nalidixic acid, chloramphenicol, and nitrofurantoin were observed. The percentage of multiple drug resistance of Pseudomonas spp. and Aeromonas spp. isolates was 96.6% and 61.9%, respectively. The multiple antibiotic resistance (MAR) index mean values of 0.457 and 0.293 of Pseudomonas and Aeromonas isolates, respectively, indicated that these isolates were exposed to high risk sources of contamination where antibiotics were commonly used. Approximately 33% of Pseudomonas spp. and 28% of Aeromonas spp. isolates from catfish contained class 1 integrons, but no class 2 integrons were detected. Several common resistance genes including aadA, dfrA and catB were harbored in class 1 integrons. Large plasmids (>55 kb) were frequently detected in 50% and 71.4% of the plasmids extracted from Pseudomonas and Aeromonas isolates, respectively. Conjugation and transformation experiments demonstrated the successful transfer of all or part of the resistance phenotypes of catfish isolates to the recipient strains, including laboratory strains and strains isolated from this study. These results highlight the likely role of catfish bacteria as a reservoir of antibiotic resistant, Gram-negative bacteria harboring a pool of mobile genetic elements that can readily be transferred intra- and interspecies. To our knowledge, this is the first report on molecular characterization of antibiotic resistance of bacteria isolated from catfish in Vietnam.

  17. Serologic and molecular survey for hepatitis E virus in wild boar (Sus scrofa) in Central Italy

    PubMed Central

    Mazzei, M.; Nardini, R.; Verin, R.; Forzan, M.; Poli, A.; Tolari, F.

    2015-01-01

    The aim of this study was to further investigate the role of wild boar (Sus scrofa) as a reservoir for hepatitis E virus (HEV). Sixty-four blood and faecal samples collected from wild boar hunted in Central Italy in 2011–2012 were examined by indirect enzyme-linked immunosorbent assay and RT-PCR analysis. Positive RT-PCR samples were further examined by nucleotide sequence determination and subsequent phylogenetic analysis. Thirty-six sera (56.2%) were positive for HEV-specific antibodies, and six (9.4%) faecal samples scored RT-PCR-positive results. Four animals were positive by both enzyme-linked immunosorbent assay and RT-PCR. Phylogenetic analysis showed that the detected wild boar–derived HEV sequences clustered within genotype 3, with similarity to sequences of human origin collected in a nearby area in 2012. Our data confirm that HEV is endemic in the wild boar population in the research area and that these wild animals could play an important role in the epidemiology of HEV infection. PMID:26199731

  18. Single-step PCR in molecular diagnosis of hepatitis C virus infection.

    PubMed Central

    Farma, E; Boeri, E; Bettini, P; Repetto, C M; McDermott, J; Lillo, F B; Varnier, O E

    1996-01-01

    The diagnostic utility of two PCR systems and three PCR detection methods for hepatitis C virus (HCV) RNA was evaluated in serum samples. A nested PCR was considered the reference assay and was compared with two single-step PCR methods: the first is based on the detection of PCR products by liquid hybridization with a 32P-end-labeled probe, and the second is the Roche Amplicor colorimetric assay using microwell plate hybridization with a specific nucleic acid probe. Using the Pelicheck HCV RNA Eurohep genotype 1 proficiency panel, our laboratory achieved medium-high levels of performance with all three methods. The highest sensitivity was, however, observed with the isotopic single-step PCR (ss-PCR) method. The analytical sensitivity of ss-PCR with isotopic detection and ss-PCR with colorimetric detection was identical to that of nested PCR, with a 100% result concordance. Comparison of ss-PCR with enzyme-linked immunosorbent and RIBA assays in the analysis of clinical samples showed a high concordance. ss-PCR methods appear more suitable for diagnostic application. Nevertheless, HCV RNA PCR cannot be considered a screening assay; it should be requested in the presence of reactive serology or specific clinical symptomatology with altered liver parameters, and it is a potential tool for the follow-up of patients with HCV infection. PMID:8940466

  19. Molecular characterization of hepatitis c virus in multi-transfused Colombian patients

    PubMed Central

    2012-01-01

    Background Hepatitis C virus (HCV) infects 170 million persons worldwide and is a public health problem. Considering that HCV is principally transmitted by exposure to infected blood, multi-transfused patients constitute one of the most important risk groups in developing countries. To explore the dynamics of this infection in Colombia, we performed a study to determine the genotypes of HCV in a cohort of multi-transfused patients. Results The serum samples from patients positive for anti-HCV were evaluated for HCV RNA by nested-PCR of the 5’untranslated region (5’UTR). Viral genotype was determined by RFLP and/or automated sequencing. HCV subtype 1b was found in eight cases (66.7%) and subtype 1a in two cases (16.7%); seven isolates of subtype 1b were obtained from patients who had received the first transfusion before 1986. Either genotypes 2b (8.3%) or 3a (8.3%) were found in the remaining positive specimens. Conclusions This is the first HCV genotyping study developed in multi-transfused patients in Colombia where HCV subtype 1b was the most prevalent. The mutation G235A in the 5’UTR of three isolates generated an additional restriction site and an RFLP pattern different from those previously described for genotype 1. PMID:23088845

  20. Molecular Evolution of Hepatitis A Virus: a New Classification Based on the Complete VP1 Protein

    PubMed Central

    Costa-Mattioli, Mauro; Cristina, Juan; Romero, Héctor; Perez-Bercof, Raoul; Casane, Didier; Colina, Rodney; Garcia, Laura; Vega, Ines; Glikman, Graciela; Romanowsky, Victor; Castello, Alejandro; Nicand, Elisabeth; Gassin, Michelle; Billaudel, Sylviane; Ferré, Virginie

    2002-01-01

    Hepatitis A virus (HAV) is a positive-stranded RNA virus in the genus Hepatovirus in the family Picornaviridae. So far, analysis of the genetic variability of HAV has been based on two discrete regions, the VP1/2A junction and the VP1 N terminus. In this report, we determined the nucleotide and deduced amino acid sequences of the complete VP1 gene of 81 strains from France, Kosovo, Mexico, Argentina, Chile, and Uruguay and compared them with the sequences of seven strains of HAV isolated elsewhere. Overall strain variation in the complete VP1 gene was found to be as high as 23.7% at the nucleotide level and 10.5% at the amino acid level. Different phylogenetic methods revealed that HAV sequences form five distinct and well-supported genetic lineages. Within these lineages, HAV sequences clustered by geographical origin only for European strains. The analysis of the complete VP1 gene allowed insight into the mode of evolution of HAV and revealed the emergence of a novel variant with a 15-amino-acid deletion located on the VP1 region where neutralization escape mutations were found. This could be the first antigenic variant of HAV so far identified. PMID:12186933

  1. Serologic and molecular survey for hepatitis E virus in wild boar (Sus scrofa) in Central Italy.

    PubMed

    Mazzei, M; Nardini, R; Verin, R; Forzan, M; Poli, A; Tolari, F

    2015-09-01

    The aim of this study was to further investigate the role of wild boar (Sus scrofa) as a reservoir for hepatitis E virus (HEV). Sixty-four blood and faecal samples collected from wild boar hunted in Central Italy in 2011-2012 were examined by indirect enzyme-linked immunosorbent assay and RT-PCR analysis. Positive RT-PCR samples were further examined by nucleotide sequence determination and subsequent phylogenetic analysis. Thirty-six sera (56.2%) were positive for HEV-specific antibodies, and six (9.4%) faecal samples scored RT-PCR-positive results. Four animals were positive by both enzyme-linked immunosorbent assay and RT-PCR. Phylogenetic analysis showed that the detected wild boar-derived HEV sequences clustered within genotype 3, with similarity to sequences of human origin collected in a nearby area in 2012. Our data confirm that HEV is endemic in the wild boar population in the research area and that these wild animals could play an important role in the epidemiology of HEV infection.

  2. Long chain acyl-CoA synthetase-3 is a molecular target for peroxisome proliferator-activated receptor delta in HepG2 hepatoma cells.

    PubMed

    Cao, Aiqin; Li, Hai; Zhou, Yue; Wu, Minhao; Liu, Jingwen

    2010-05-28

    ACSL3 is a member of the long chain acyl-CoA synthetase (ACSL) family that plays key roles in fatty acid metabolism in various tissues in an isozyme-specific manner. Our previous studies showed that ACSL3 was transcriptionally up-regulated by the cytokine oncostatin M (OSM) in HepG2 cells, accompanied by reduced cellular triglyceride content and enhanced beta-oxidation. In this study, we investigated the molecular mechanism underlying the OSM-induced activation of ACSL3 gene transcription in HepG2 cells. We showed that OSM treatment resulted in a coordinated elevation of mRNA levels of ACSL3 and peroxisome proliferator-activated receptor delta (PPARdelta). The effect of OSM on ACSL3 mRNA expression was inhibited by cellular depletion of PPARdelta. By utilizing a PPARdelta agonist, L165041, we demonstrated that activation of PPARdelta led to increases in ACSL3 promoter activity, mRNA level, and protein level in HepG2 cells. Analysis of the ACSL3 promoter sequence identified two imperfect PPAR-responsive elements (PPRE) located in the ACSL3 promoter region -944 to -915, relative to the transcription start site. The up-regulation of ACSL3 promoter activity by PPARdelta was abolished by deletion of this PPRE-containing region or mutation to disrupt the binding sites. Direct interactions of PPARdelta with ACSL3-PPRE sequences were demonstrated by gel mobility shift and chromatin immunoprecipitation assays. Finally, we provided in vivo evidence showing that activation of PPARdelta by L165041 in hamsters increased ACSL3 mRNA and protein levels in the liver. These new findings define ACSL3 as a novel molecular target of PPARdelta in HepG2 cells and provide a regulatory mechanism for ACSL3 transcription in liver tissue.

  3. Molecular metals based on 1,2,7,8-tetrahydrodicyclopenta[cd:lm]perylene and iodine, (CPP){sub 2}(I{sub 3}){sub 1-{delta}}

    SciTech Connect

    Morgado, J. |; Santos, I.C.; Henriques, R.T.; Almeida, M.; Fourmigue, M.; Matias, P.; Veiros, L.F.; Duarte, M.T.; Alcacer, L.; Calhorda, M.J. |

    1994-12-01

    The synthesis and characterization of molecular metals derived from 1,2,7,8-tetrahydrodicyclopenta[cd:lm]perylene (CPP) by partial oxidation with iodine and with general formula (CPP){sub 2}(I{sub 3}){sub 1-{delta}}, {delta} = 0-0.13, are reported. Single crystals, obtained either by electrocrystallization or by diffusion-controlled iodine oxidation of CPP, present two types of morphologies, elongated diamond or thinner needle-shaped crystals, both with a monoclinic cell, space group P2{sub 1}/a, a = 4.3757(9), b = 19.3681(11), c = 10.0860(11) {angstrom}, {beta} = 98.050(8){degrees}, V = 846.4(2) {angstrom}{sup 3}, Z = 2. The structure of the diamond-shaped crystal was solved by X-ray diffraction to a final R(F) = 0.096, R{sub w}(F) = 0.069. It consists of regular stacks of CPP molecules along a with a 3.41 {angstrom} spacing and uncorrected one-dimensional chains of I{sub 3}{sup {minus}} located in channels between four CPP stacks corresponding to (CPP){sub 2}(I{sub 3}){sub 0.892}. The thin needle crystals have the same unit cell but an unspecified and slightly different iodine content. Band structure calculations in this structure by the extended Hueckel method indicate a one-dimensional conduction band 0.55 eV wide. These thin needle crystals present, at room temperature, an electrical conductivity along the a axis {alpha}{sub a}(RT) = 200 S/cm and thermopower S{sub a}(RT) = 30 {mu}V/K, while for the diamond-shaped crystals {alpha}{sub a}(RT) = 2 S/cm and S{sub a}(RT) = -8 {mu}V/K. These transport coefficients for both types of crystals indicate a metallic behavior from room temperature down to {approx_equal}63 K, where a metal-to-insular (M-I) transition takes place. EPR studies in single crystals show an almost isotropic line at g = 2.0044 and with a width of {approx_equal}6 G in the range 80-300 K and without significant differences between the two types of crystals. 53 refs., 9 figs., 4 tabs.

  4. Phenethyl amides as novel noncovalent inhibitors of hepatitis C virus NS3/4A protease: discovery, initial SAR, and molecular modeling.

    PubMed

    Colarusso, Stefania; Koch, Uwe; Gerlach, Benjamin; Steinkühler, Christian; De Francesco, Raffaele; Altamura, Sergio; Matassa, Victor G; Narjes, Frank

    2003-01-30

    The discovery of novel, reversible and competitive tripeptide inhibitors of the Hepatitis C virus NS3/4A serine protease is described. These inhibitors are characterized by the presence of a C-terminal phenethyl amide group, which extends into the prime side of the enzyme. Initial SAR together with molecular modeling and data from site-directed mutagenesis suggest an interaction of the phenethyl amide group with Lys-136.

  5. Understanding the molecular mechanism(s) of hepatitis C virus (HCV) induced interferon resistance.

    PubMed

    Qashqari, Hanadi; Al-Mars, Amany; Chaudhary, Adeel; Abuzenadah, Adel; Damanhouri, Ghazi; Alqahtani, Mohammed; Mahmoud, Maged; El Sayed Zaki, Maysaa; Fatima, Kaneez; Qadri, Ishtiaq

    2013-10-01

    Hepatitis C virus (HCV) is one of the foremost causes of chronic liver disease affecting over 300 million globally. HCV contains a positive-stranded RNA of ~9600 nt and is surrounded by the 5' and 3'untranslated regions (UTR). The only successful treatment regimen includes interferon (IFN) and ribavirin. Like many other viruses, HCV has also evolved various mechanisms to circumvent the IFN response by blocking (1) downstream signaling actions via STAT1, STAT2, IRF9 and JAK-STAT pathways and (2) repertoire of IFN Stimulatory Genes (ISGs). Several studies have identified complex host demographic and genetic factors as well as viral genetic heterogeneity associated with outcomes of IFN therapy. The genetic predispositions of over 2000 ISGS may render the patients to become resistant, thus identification of such parameters within a subset of population are necessary for management corollary. The ability of various HCV genotypes to diminish IFN antiviral responses plays critical role in the establishment of chronic infection at the acute stage of infection, thus highlighting importance of the resistance in HCV treated groups. The recently defined role of viral protein such as C, E2, NS3/NS4 and NS5A proteins in inducing the IFN resistance are discussed in this article. How the viral and host genetic composition and epistatic connectivity among polymorphic genomic sites synchronizes the evolutionary IFN resistance trend remains under investigation. However, these signals may have the potential to be employed for accurate prediction of therapeutic outcomes. In this review article, we accentuate the significance of host and viral components in IFN resistance with the aim to determine the successful outcome in patients.

  6. Molecular analysis of hepatitis B virus "a" determinant in asymptomatic and symptomatic Mexican carriers

    PubMed Central

    Ruiz-Tachiquín, Martha-Eugenia; Valdez-Salazar, Hilda-Alicia; Juárez-Barreto, Vicencio; Dehesa-Violante, Margarita; Torres, Javier; Muñoz-Hernández, Onofre; Alvarez-Muñoz, Ma-Teresa

    2007-01-01

    Background Hepatitis B virus (HBV) is a small DNA-containing virus with 4 genes, C, S, X and P. The S gene codes for the surface antigen (HBsAg), which contains the "a" determinant, the main region for induction of a protective humoral immune response. To compare the genotype and sequence of the "a" determinant between strains isolated from asymptomatic and symptomatic Mexican HBV carriers. Results 21 asymptomatic (blood donors) and 12 symptomatic (with clinical signs and with >1 year lamivudine treatment) HBV carriers were studied; all patients were positive for the HBsAg in serum. Viral load, genotypes, and subtypes were determined in plasma. A fragment of the S gene including the "a" determinant was PCR amplified and sequenced to determine genotype, subtype and to identify mutations. Mean viral load was 0.7965 × 104 copies/ml in asymptomatic carriers and 2.73 × 106 copies/ml in symptomatic patients. Genotypes H, C, and F were identified in asymptomatic individuals; whereas H was dominant in symptomatic patients. A fragment of 279 bp containing the "a" determinant was amplified from all 33 carriers and sequences aligned with S gene sequences in the GenBank. Mutations identified were Y100N, T126I, Q129H and N146K in the asymptomatic group, and F93I and A128V in the symptomatic group. Conclusion Differences in genotype and in mutations in the "a" determinant were found between strains from asymptomatic and symptomatic HBV Mexican carriers. PMID:17217533

  7. Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina

    PubMed Central

    Rodrigo, María Belén; Mojsiejczuk, Laura Noelia; Torres, Carolina; Sevic, Ina; González López Ledesma, María Mora; Perez, Paula Soledad; Bouzas, María Belén; Galdame, Omar; Marciano, Sebastián; Fainboim, Hugo; Flichman, Diego Martín; Campos, Rodolfo Héctor

    2016-01-01

    Hepatitis B virus (HBV) is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H) with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%), A2 (18.2%), F4 (18.2%) and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases. PMID:27433800

  8. Analysis of the Molecular Evolution of Hepatitis B Virus Genotypes in Symptomatic Acute Infections in Argentina.

    PubMed

    Rodrigo, María Belén; Mojsiejczuk, Laura Noelia; Torres, Carolina; Sevic, Ina; González López Ledesma, María Mora; Perez, Paula Soledad; Bouzas, María Belén; Galdame, Omar; Marciano, Sebastián; Fainboim, Hugo; Flichman, Diego Martín; Campos, Rodolfo Héctor

    2016-01-01

    Hepatitis B virus (HBV) is a globally distributed human pathogen that leads to both self-limited and chronic infections. At least eight genotypes (A-H) with distinct geographical allocations and phylodynamic behaviors have been described. They differ substantially in many virological and probably some clinical parameters. The aim of this study was to analyze full-length HBV genome sequences from individuals with symptomatic acute HBV infections using phylogenetic and coalescent methods. The phylogenetic analysis resulted in the following subgenotype distribution: F1b (52.7%), A2 (18.2%), F4 (18.2%) and A1, B2, D3 and F2a 1.8% each. These results contrast with those previously reported from chronic infections, where subgenotypes F1b, F4, A2 and genotype D were evenly distributed. This differential distribution might be related to recent internal migrations and/or intrinsic biological features of each viral genotype that could impact on the probability of transmission. The coalescence analysis showed that after a diversification process started in the 80s, the current sequences of subgenotype F1b were grouped in at least four highly supported lineages, whereas subgenotype F4 revealed a more limited diversification pattern with most lineages without offspring in the present. In addition, the genetic characterization of the studied sequences showed that only two of them presented mutations of clinical relevance at S codifyng region and none at the polymerase catalytic domains. Finally, since the acute infections could be an expression of the genotypes currently being transmitted to new hosts, the predominance of subgenotype F1b might have epidemiological, as well as, clinical relevance due to its potential adverse disease outcome among the chronic cases.

  9. Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: Application to diagnosis and blood screening for posttransfusion hepatitis

    SciTech Connect

    Miyamura, Tatsuo; Saito, Izumu ); Katayama, Tohru ); Kikuchi, Shu; Tateda, Akira ); Houghton, M.; Choo, Quilim; Kuo, G. )

    1990-02-01

    A cDNA clone has been derived from the plasma of a chimpanzee with chronic non-A, non-B viral hepatits (NANBH). The authors have assayed for antibodies reacting with the encoded antigen in sera from posttransfusion hepatitis patients (643 samples from 23 patients) and their corresponding donors collected during the past 10 years in Japan. The antibody was detected in 15 out of 17 (88.2%) posttransfusion NANBH (PT-NANBH) patients whose sera over time displayed multiple alanine aminotransferase (ALT) peaks. In general, the antibody was detected after several peaks of serum ALT elevations and, once detected, it persisted for years. Of the 15 well-defined cases of PT-NANBH that showed multiple ALT peaks and hepatitis C virus seroconversions, 11 (73.3%) were shown to be transfused with at least one unit of blood positive for the antibody. The retrospective analysis showed that all tested donor blood found to be positive for the antibody had been transfused to recipients who afterwards developed NANBH. These data strongly suggest that the cloned cDNA originated from an etiological agent of NANBH termed the hepatitis C virus. Furthermore, the present study demonstrates that had the screening been done with the anti-hepatitis C virus assay, 11 out of 17 (64.7%) cases of chronic PT-NANBH and 1 out of 6 (16.6%) acute PT-NANBH would have been prevented.

  10. Mississippi Delta

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The streamers of clouds draped over the Gulf of Mexico in this true-color MODIS image from February 27, 2002, suggest that a cold, dry wind was blowing southward over the United States and began to pick up moisture over the Gulf, causing these strips of clouds. That the clouds didn't pick up until some distance from the coastline allowed MODIS to get a perfect view of the dynamic Gulf Coast environment spanning (left to right) Texas, Louisiana, Mississippi, Alabama, and Florida's Western Panhandle. The Mississippi River runs roughly down the center of the image, and is joined in Louisiana by the Red River coming in from the northwest. Over the past 7000 years, the actual delta, where the main river channel empties into the Gulf, has wandered around what we now think of as the Louisiana coast. Considering all the sediment visible in this image, it's not hard to imagine that the river carries about 2.4 billion kilograms of sediment into the Gulf each year. Deposition of some of this sediment has been building up the current delta, called the Birdfoot Delta, for obvious reasons, for about 700 years. The coastal waters are alive with microscopic organisms called phytoplankton, which contain colorful pigments, including chlorophyll, for harvesting sunlight. Beyond the sediment plume off Louisiana, the waters are very dark, which could indicate that a large amount of chlorophyll is present, absorbing lots of sunlight and causing the water to appear dark. Farther south, the waters appear bright blue, which could be a signature of coccolithophores, which use highly reflective calcium carbonate to build scaly coverings for themselves. The brighter offshore waters could also be caused by a blue-green algae called Trichodesmium, an organism that can not only harness carbon dioxide for photosynthesis, but can also take nitrogen from the air and turn it into a form that can be used by living organisms. Credit: Jacques Descloitres, MODIS Land Rapid Response Team, NASA/GSFC

  11. Hepatitis C

    MedlinePlus

    ... Châu và vùng Thái Bình Dương Hepatitis C Hepatitis C What is hepatitis C? Hepatitis C is a viral infection that ... can cure most cases of hepatitis C. Acute hepatitis C Acute hepatitis C is a short-term ...

  12. Hepatitis A

    MedlinePlus

    ... Châu và vùng Thái Bình Dương Hepatitis C Hepatitis A What is hepatitis A? Hepatitis A is a viral infection that ... spreading hepatitis A to others . How common is hepatitis A? In the United States, hepatitis A has ...

  13. Hepatitis B

    MedlinePlus

    ... Châu và vùng Thái Bình Dương Hepatitis C Hepatitis B What is hepatitis B? Hepatitis B is a viral infection that ... to prevent spreading hepatitis B to others . Acute hepatitis B Acute hepatitis B is a short-term ...

  14. Genotype I of hepatitis B virus was found in east Xishuangbanna, China and molecular dynamics of HBV/I.

    PubMed

    Shen, T; Yan, X M; Liu, H X; Zhang, B X; Li, L; Zhang, J P; Wang, J L; Xiao, C J

    2015-01-01

    There is a dearth of data about the prevalence of hepatitis B virus (HBV) infection in Mengla, China; and no detailed analysis of the molecular evolution of genotype I in Asia. In this study, 909 serum samples from ethnic minority people in China were obtained. Serological assay and HBV S-gene amplification were carried out, and phylogenetic and evolutionary dynamics analysis of 62 HBV/I S-gene was performed. On this survey, 153 individuals were tested HBsAg-positive. Genotypes of S-gene were classified into three groups: C, B and I. Under the strict model and the relax model, the estimated evolutionary rates for HBV/I were 3.74 × 10(-4) and 6.93 × 10(-4) substitution/site/year, respectively. However, when the geographic origin was taken into account, the mean substitution rates were increased. Estimated time to most recent ancestor of genotype I varied from ~30 to ~70 years ago. The Bayesian sky plot showed a rapid spread of HBV/I at the end of 1980s. Peculiar nucleotides distributed were observed in the subgenotype I1/I2. In conclusion, higher prevalence of HBV infection was observed in Mengla county. Multifactors like timescale and spatial locations should be integrated to provide a better interpretation of the HBV/I evolutionary history in the region.

  15. Modulating the interaction of CXCR4 and CXCL12 by low-molecular-weight heparin inhibits hepatic metastasis of colon cancer.

    PubMed

    Ma, Lixin; Qiao, Haiquan; He, Changjun; Yang, Qian; Cheung, Chun Hei Antonio; Kanwar, Jagat R; Sun, Xueying

    2012-04-01

    Liver metastasis is the major obstacle for prolonging the survival of colon cancer patients. Low-molecular-weight heparin (LMWH), a common drug for venous thromboembolism, has displayed beneficial effects in improving the survival of cancer patients, though the mechanism remains unclear. This study aimed to investigate the effects of LMWH on hepatic metastasis of colon cancer and its underlying molecular mechanism by targeting the interaction of the chemokine receptor CXCR4 and its ligand CXCL12 (formerly known as stromal cell-derived factor 1α, SDF-1α), as the CXCR4-CXCL12 axis has been shown to regulate the interaction of cancer cells and stroma. Experimental results revealed that LMWH (Enoxaparin, 3500-5500 Da) inhibited the CXCL12-stimulated proliferation, adhesion and colony formation of human colon cancer HCT-116 cells that highly expressed CXCR4. Interestingly, LMWH or an anti-CXCR4 blocking antibody diminished the migrating and invading abilities of HCT116 cells stimulated by the recombinant CXCL12 protein or liver homogenates which contained endogenous CXCL12 protein. Although LMWH did not significantly inhibit the growth of subcutaneous colon tumors, it significantly suppressed the formation of hepatic metastasis established by intrasplenic injection of colon cancer cells in nude Balb/c mice and also downregulated the expression of CXCL12 in hepatic sinusoidal endothelial cells. The results suggest that LMWH inhibits the formation of hepatic metastasis of colon cancer by disrupting the interaction of CXCR4 and CXCL12, supporting that perioperative administration of LMWH may help to prevent the seeding and subsequent growth of hepatic metastases of colon cancer cells.

  16. Serum haptoglobin as a novel molecular biomarker predicting colorectal cancer hepatic metastasis.

    PubMed

    Sun, Lichao; Hu, Shusheng; Yu, Long; Guo, Chunguang; Sun, Lixin; Yang, Zhihua; Qi, Jun; Ran, Yuliang

    2016-06-01

    Early detection of liver metastasis is important for improving colorectal cancer (CRC) patient survival. Our previous studies showed haptoglobin was highly expressed in primary CRC tissues, especially in heterochronous metastatic cases. Here, we assessed the potential of serum haptoglobin (sHP) as a biomarker for early detection of CRC liver metastasis by evaluating the sHP in 475 CRC patients and 152 healthy volunteers. In the training set (250 cases), sHP level in CRC-M1 (1773.18 ± 690.25 ng/mL) were significantly increased as compared to in CRC-M0 (1544.37 ± 1497.65 ng/mL) or healthy (917.76 ± 571.59 ng/mL). And the high sHP level was correlated with poor survival. Logistic regression analysis revealed that sHP, serum carcinoembryonic antigen (sCEA) and serum carbohydrate antigen 19.9 (sCA19.9) level were the significant parameters for detecting liver metastasis. In leave-one-out-cross-validation, these three markers resulted in 89.1% sensitivity and 85.8% specificity for hepatic metastasis detection. In an independent test set (225 cases), receiver operating characteristic curve analysis of sHP in CRC liver metastasis showed an area under the curve of 0.735, with a sensitivity of 87.2% and a specificity of 59.9%. Combination of sHP, sCEA and sCA19.9 improved diagnostic accuracy to 0.880, with a sensitivity of 88.5% and a specificity of 87.8%. Silencing of HP by specific shRNA significantly inhibited the LOVO and SW620 cell invasion, and suppressed xenograft tumor invasive growth. In summary, these results demonstrate that sHP is associated with poor prognosis of CRC patients and that HP promotes colorectal cancer cell invasion. sHP combining with sCA19.9 and sCEA may be used as accurate predictors of CRC liver metastasis.

  17. [Dosing time based on molecular mechanism of biological clock of hepatic drug metabolic enzyme].

    PubMed

    Matsunaga, Naoya

    2009-11-01

    The mammalian circadian pacemaker stays in the paired suprachiasmatic nuclei (SCN). Recent several studies reveal that the circadian rhythms of physiology and behavior are controlled by clock genes. In addition, the effectiveness and toxicity of many drugs vary depending on dosing time associated with 24-h rhythms of biochemical, physiological, and behavioral processes under the control of the circadian clock. Acetaminophen (APAP) is a widely used analgesic drug, and is mainly biotransformed and eliminated as nontoxic conjugates with glucuronic acid and sulfuric acid. Only a small portion of the dose is mainly bioactivated by CYP2E1 to N-acetyl-p-benzoquinone imine (NAPQI), a reactive toxic intermediate. For APAP overdose, glucuronidation and sulfation are saturated and the formation of NAPQI increases. However, the exact mechanisms underlying the chronotoxicity of APAP have not been clarified yet. In the present study, we have clarified that there was a significant dosing time-dependent difference in hepatotoxicity induced by APAP in mice. The mechanism may be related to the rhythmicity of CYP2E1 activity and GSH conjugation. In additon, we investigated whether the liver transcription factor hepatic nuclear factor-1alpha (HNF-1alpha) and clock genes undergoing astriking 24-h rhythm in mouse liver contribute to the 24-h regulation of CYP2E1 activity. A significant 24-h rhythmicity was demonstrated for CYP2E1 activity, protein levels and mRNA levels. HNF-1alpha and clock genes may contribute to produce the 24-h rhythm of CYP2E1 mRNA levels. Metabolism by CYP and GSH conjugation are common metabolic pathways for many drugs such as APAP. These findings support the concept that choosing the most appropriate time of day to administer the drugs associated with metabolic rhythmicity such as CYP and GSH conjugation may reduce hepatotoxicity in experimental and clinical situations. 24-h rhythm of CYP2E1 activity was controlled by HNF-1alpha and clock gene, in a

  18. A competitor DNA template for the molecular quantification of the hepatitis B virus.

    PubMed

    Sidorkiewicz, Małgorzata; Bzorska, Aneta; Józwiak, Barbara; Jabłkowski, Maciej; Szemraj, Janusz; Lewandowska, Urszula

    2003-01-01

    The molecular determination of viral load in the serum represents the most valuable prognostic marker of HBV infection. In this paper, a new molecular assay for the quantitative measurement of HBV presence is described. It is based on PCR performing with a HBV-specific competitor DNA template. For the construction of the DNA template, a HBV DNA-originated 436 bp DNA fragment was modified by introducing a 110 bp deletion and cloned into pUC19. The resulting vector serves as the competitor DNA template in the competitive PCR. Post-PCR, the competitor DNA generates an amplified fragment of 306 bp; it could be easily distinguished from the product generated from the viral-originated DNA product (416 bp) when the same primers are used. The quantitative ratio between the two products enables the quantitative determination of viral load. The range of the HB-PCR assay is from 3 x 10(4)to 6 x 10(10) particles/ml. A serum HBV load determination performed by HB-PCR assay indicated a close correlation with the results of the Quantiplex HBV DNA assay (bDNA). The HB-PCR assay is cheap, reliable and easy to use in any laboratory working with PCR methods.

  19. Detection and Molecular Characterization of Hepatitis A Virus from Tunisian Wastewater Treatment Plants with Different Secondary Treatments

    PubMed Central

    Ouardani, Imen; Turki, Syrine; Aouni, Mahjoub

    2016-01-01

    ABSTRACT Hepatitis A virus (HAV) is the main causative agent of hepatitis infection associated with waterborne outbreaks worldwide. In Tunisia, there is no specific surveillance system for HAV and current secondary wastewater treatment processes are unable to remove viral particles, which present a potential public health problem. Qualitative and quantitative analysis of HAV in 271 raw and treated wastewater samples from five sewage treatment plants (STPs) during 13 months was performed. Moreover, the efficiency of three secondary wastewater treatment processes (conventional activated sludge, extended aeration, and oxidation ditch activated sludge) was evaluated. Data obtained demonstrated that HAV is endemic in Tunisia and circulates with high prevalence in both raw (66.9%) and treated (40.7%) wastewater. HAV circulates throughout the year in the coastal areas, with the highest rates found during summer and autumn, whereas in central Tunisia, high levels were shown in autumn and winter. Total virus removal was not achieved, since no difference in mean HAV loads was observed in effluents (6.0 × 103 genome copies [GC]/ml) and influents (2.7 × 103 GC/ml). The comparison of the HAV removal values of the three different wastewater treatment methods indicates that extended aeration and oxidation ditch activated sludge had better efficiency in removing viruses than conventional activated sludge did. Molecular characterization revealed that the vast majority of HAV strains belonged to subgenotype IA, with the cocirculation of subgenotype IB in wastewater treatment plants that collect tourism wastewater. IMPORTANCE This report provides important data on the incidence, behavior, seasonality, and genotype distribution of HAV in the environment in Tunisia, as well as the risk of infection derived from its occurrence in effluents due to inadequate wastewater treatment. In addition, these findings seem to confirm that the prevalence of HAV depends on socioeconomic level

  20. Mississippi Delta

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The Mississippi River delta teems with sediment deposited by the river as it flows into the Gulf of Mexico in this true-color image captured by MODIS on October 15, 2001. The sediment, which is marked by brown swirls in the Gulf, provides nutrients for the bloom of phytoplankton visible as blue-green swirls off the coastline. In the high-resolution image the city of Memphis can be seen in the southwest corner of Tennessee, which is just to left of center at the top of the image. The brown coloration that encompasses Memphis and either side of the river, as flows north to south along the left side of the image, is the river's flood plain. Also visible, in the upper-right hand corner of the image is the southern end of the Appalachian Mountains.

  1. Viral Hepatitis

    MedlinePlus

    ... Public Home » For Veterans and the Public Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... the Public Veterans and Public Home How is Hepatitis C Treated? Find the facts about the newest ...

  2. Autoimmune Hepatitis

    MedlinePlus

    ... Cholangitis Wilson Disease Liver Disease A-Z Autoimmune Hepatitis What is autoimmune hepatitis? Autoimmune hepatitis is a chronic—or long lasting— ... bacteria, viruses, toxins, and medications. What causes autoimmune hepatitis? A combination of autoimmunity, environmental triggers, and a ...

  3. Heteroaryldihydropyrimidine (HAP) and Sulfamoylbenzamide (SBA) Inhibit Hepatitis B Virus Replication by Different Molecular Mechanisms

    PubMed Central

    Zhou, Zheng; Hu, Taishan; Zhou, Xue; Wildum, Steffen; Garcia-Alcalde, Fernando; Xu, Zhiheng; Wu, Daitze; Mao, Yi; Tian, Xiaojun; Zhou, Yuan; Shen, Fang; Zhang, Zhisen; Tang, Guozhi; Najera, Isabel; Yang, Guang; Shen, Hong C.; Young, John A. T.; Qin, Ning

    2017-01-01

    Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) are promising non-nucleos(t)ide HBV replication inhibitors. HAPs are known to promote core protein mis-assembly, but the molecular mechanism of abnormal assembly is still elusive. Likewise, the assembly status of core protein induced by SBA remains unknown. Here we show that SBA, unlike HAP, does not promote core protein mis-assembly. Interestingly, two reference compounds HAP_R01 and SBA_R01 bind to the same pocket at the dimer-dimer interface in the crystal structures of core protein Y132A hexamer. The striking difference lies in a unique hydrophobic subpocket that is occupied by the thiazole group of HAP_R01, but is unperturbed by SBA_R01. Photoaffinity labeling confirms the HAP_R01 binding pose at the dimer-dimer interface on capsid and suggests a new mechanism of HAP-induced mis-assembly. Based on the common features in crystal structures we predict that T33 mutations generate similar susceptibility changes to both compounds. In contrast, mutations at positions in close contact with HAP-specific groups (P25A, P25S, or V124F) only reduce susceptibility to HAP_R01, but not to SBA_R01. Thus, HAP and SBA are likely to have distinctive resistance profiles. Notably, P25S and V124F substitutions exist in low-abundance quasispecies in treatment-naïve patients, suggesting potential clinical relevance. PMID:28205569

  4. Acute molecular markers of rodent hepatic carcinogenesis identified by transcription profiling.

    PubMed

    Kramer, Jeffrey A; Curtiss, Sandra W; Kolaja, Kyle L; Alden, Carl L; Blomme, Eric A G; Curtiss, William C; Davila, Julio C; Jackson, Carmen J; Bunch, Roderick T

    2004-04-01

    Currently, the only way to identify nongenotoxic hepatocarcinogens is through long-term repeat dose studies such as the 2 year rodent carcinogenicity assay. Such assays are both time consuming and expensive and require large amounts of active pharmaceutical or chemical ingredients. Thus, the results of the 2 year assay are not known until very late in the discovery and development process for new pharmaceutical entities. Although in many cases nongenotoxic carcinogenicity in rodents is considered to be irrelevant for humans, a positive finding in a 2 year carcinogenicity assay may increase the number of studies to demonstrate the lack of relevance to humans, delay final submission and subsequent registration of a product, and may result in a "black box" carcinogenicity warning on the label. To develop early identifiers of carcinogenicity, we applied transcription profiling using several prototype rodent genotoxic and nongenotoxic carcinogens, as well as two noncarcinogenic hepatotoxicants, in a 5 day repeat dose in vivo toxicology study. Fluorescent-labeled probes generated from liver mRNA prepared from male Sprague-Dawley rats treated with one of three dose levels of bemitradine, clofibrate, doxylamine, methapyrilene, phenobarbital, tamoxifen, 2-acetylaminofluorene, 4-acetylaminofluorene, or isoniazid were hybridized against rat cDNA microarrays. Correlation of the resulting data with an estimated carcinogenic potential of each compound and dose level identified several candidate molecular markers of rodent nongenotoxic carcinogenicity, including transforming growth factor-beta stimulated clone 22 and NAD(P)H cytochrome P450 oxidoreductase.

  5. Viral Hepatitis

    MedlinePlus

    ... with hepatitis? How does a pregnant woman pass hepatitis B virus to her baby? If I have hepatitis B, what does my baby need so that she ... Can I breastfeed my baby if I have hepatitis B? More information on viral hepatitis What is hepatitis? ...

  6. Algorithmic Approach to High-Throughput Molecular Screening for Alpha Interferon-Resistant Genotypes in Hepatitis C Patients

    PubMed Central

    Sreevatsan, Srinand; Bookout, Jack B.; Ringpis, Fidel M.; Pottathil, Mridula R.; Marshall, David J.; De Arruda, Monika; Murvine, Christopher; Fors, Lance; Pottathil, Raveendran M.; Barathur, Raj R.

    1998-01-01

    This study was designed to analyze the feasibility and validity of using Cleavase Fragment Length Polymorphism (CFLP) analysis as an alternative to DNA sequencing for high-throughput screening of hepatitis C virus (HCV) genotypes in a high-volume molecular pathology laboratory setting. By using a 244-bp amplicon from the 5′ untranslated region of the HCV genome, 61 clinical samples received for HCV reverse transcription-PCR (RT-PCR) were genotyped by this method. The genotype frequencies assigned by the CFLP method were 44.3% for type 1a, 26.2% for 1b, 13.1% for type 2b, and 5% type 3a. The results obtained by nucleotide sequence analysis provided 100% concordance with those obtained by CFLP analysis at the major genotype level, with resolvable differences as to subtype designations for five samples. CFLP analysis-derived HCV genotype frequencies also concurred with the national estimates (N. N. Zein et al., Ann. Intern. Med. 125:634–639, 1996). Reanalysis of 42 of these samples in parallel in a different research laboratory reproduced the CFLP fingerprints for 100% of the samples. Similarly, the major subtype designations for 19 samples subjected to different incubation temperature-time conditions were also 100% reproducible. Comparative cost analysis for genotyping of HCV by line probe assay, CFLP analysis, and automated DNA sequencing indicated that the average cost per amplicon was lowest for CFLP analysis, at $20 (direct costs). On the basis of these findings we propose that CFLP analysis is a robust, sensitive, specific, and an economical method for large-scale screening of HCV-infected patients for alpha interferon-resistant HCV genotypes. The paper describes an algorithm that uses as a reflex test the RT-PCR-based qualitative screening of samples for HCV detection and also addresses genotypes that are ambiguous. PMID:9650932

  7. Molecular Tracing of Hepatitis C Virus Genotype 1 Isolates in Iran: A NS5B Phylogenetic Analysis with Systematic Review

    PubMed Central

    Hesamizadeh, Khashayar; Alavian, Seyed Moayed; Najafi Tireh Shabankareh, Azar; Sharafi, Heidar

    2016-01-01

    Context Hepatitis C virus (HCV) is characterized by a high degree of genetic heterogeneity and classified into 7 genotypes and different subtypes. It heterogeneously distributed through various risk groups and geographical regions. A well-established phylogenetic relationship can simplify the tracing of HCV hierarchical strata into geographical regions. The current study aimed to find genetic phylogeny of subtypes 1a and 1b of HCV isolates based on NS5B nucleotide sequences in Iran and other members of Eastern Mediterranean regional office of world health organization, as well as other Middle Eastern countries, with a systematic review of available published and unpublished studies. Evidence Acquisition The phylogenetic analyses were performed based on the nucleotide sequences of NS5B gene of HCV genotype 1 (HCV-1), which were registered in the GenBank database. The literature review was performed in two steps: 1) searching studies evaluating the NS5B sequences of HCV-1, on PubMed, Scopus, and Web of Science, and 2) Searching sequences of unpublished studies registered in the GenBank database. Results In this study, 442 sequences from HCV-1a and 232 from HCV-1b underwent phylogenetic analysis. Phylogenetic analysis of all sequences revealed different clusters in the phylogenetic trees. The results showed that the proportion of HCV-1a and -1b isolates from Iranian patients probably originated from domestic sources. Moreover, the HCV-1b isolates from Iranian patients may have similarities with the European ones. Conclusions In this study, phylogenetic reconstruction of HCV-1 sequences clearly indicated for molecular tracing and ancestral relationships of the HCV genotypes in Iran, and showed the likelihood of domestic origin for HCV-1a and various origin for HCV-1b. PMID:28123445

  8. Molecular epidemiology and genetic diversity of hepatitis B virus in Mar del Plata city, Argentina.

    PubMed

    Barbini, Luciana; Elizalde, Mercedes; Torres, Carolina; Campos, Rodolfo

    2013-10-01

    The aim of this work was to describe the current molecular epidemiology and genetic diversity of HBV in Mar del Plata, an important Argentinean touristic city. The phylogenetic analysis of 29 HBV DNA positive serum samples showed that F1b was the predominant subgenotype (sgt, 62.1%), followed by sgt A2 (13.8%) and sgt F4, gt D and gt G (6.9% each). Among anti-HBc IgM positive samples, 75.0% were sgt F1b, followed by sgt F4 (12.5%), sgt A2 (6.25%) and sgt D (6.25%). Three recombinant full length genomes were found: two G/F1b (some of the first gt G detected in Argentina) and one F4/D2. The circulation of clinical important mutations in the city was described. Mutations at the HBsAg were detected in 34.5% of the analyzed samples, associated with laboratory diagnosis and antiviral treatment failures, immune escape and hepatocellular carcinoma. Most of the samples presented wild type BCP/PC sequences. Coalescence analysis for the most prevalent sgt F1b estimated that the diversification mainly occured during mid '90s and the tMRCA was estimated in 1987. Finally, the high presence of the autochthonous sgt F1b, associated with the anti-HBc IgM positive infection and its present-day diversification process, shows the strong impact of internal human migratory movements into the current population of Mar del Plata.

  9. Molecular Characterization of Pre-Core/Core and S Region of Hepatitis B Virus in Hemodialysis Patients With Occult Hepatitis B Infection

    PubMed Central

    Rastegarvand, Nasrin; Makvandi, Manoochehr; Samarbafzadeh, Alireza; Rasti, Mojtaba; Neisi, Niloofar; Pouremamali, Amir; Teimoori, Ali; Shabani, Abdolnabi

    2015-01-01

    Background: Occult hepatitis B infection (OBI) is a major public health problem worldwide, which harbors potential risk of hepatitis B virus (HBV) transmission through blood transfusion and transplantation. OBI is characterized by the presence of HBV-DNA in the blood or liver tissue without detectable hepatitis B surface antigen (HBsAg) in the serum. An important cause of OBI is the occurrence of mutations in the HBV genome, especially in the S region. Objectives: The study aims to analyze mutations in S and pre-core/core regions of HBV-DNA in hemodialysis patients. Patients and Methods: Sera of 216 hemodialysis patients were tested for HBsAg and hepatitis B core antibody (HBcAb) by ELISA. Sera of patients that tested negative for HBsAg were evaluated by PCR for the detection of HBV-DNA in the S and pre-core/core regions. In total, six PCR products were sequenced, aligned, and compared with the HBV reference sequence. Amino acid deletion and nucleotide substitution were considered mutations in S and pre-core/core regions of HBV-DNA. Results: Among 216 patients, 203 (93.98%) and 175 (81.01%) sera samples tested negative for HBsAg and HBcAb, respectively. Among all HBsAg-negative samples, six (2.9%) tested positive for HBV-DNA, including four (1.97%) for S and two (0.98%) for pre-core regions. All four (1.97%) samples that tested positive for the S region belonged to HBV-subtype awy. The amino acid sequence of all four samples showed the YMDD motif in position 204 (rtM204). There were three amino acid substitutions in the S region (T127P, P153L, and F170S) and one substitution in the RT region (Y135S). Moreover, two (0.98%) pre-core/core positive patients had an unexpected stop codon in position 1896. Conclusions: This study indicates that 2.9% of hemodialysis patients had OBI, which is considered as a major public health problem worldwide. Moreover, we observed three mutations in S region, including T127P, P153L, and F170S, which caused OBI. This study is first to

  10. Molecular involvement of the pvt-1 locus in a gamma/delta T-cell leukemia bearing a variant t(8;14)(q24;q11) translocation.

    PubMed Central

    Kasai, M; Maziarz, R T; Aoki, K; Macintyre, E; Strominger, J L

    1992-01-01

    A highly malignant human T-cell receptor (TCR) gamma/delta+ T-cell leukemia was shown to have a productive rearrangement of the TCR delta locus on one chromosome 14 and a novel t(8;14)(q24;q11) rearrangement involving the J delta 1 gene segment on the other chromosome 14. Chromosome walking coupled with pulsed-field gel electrophoretic (PFGE) analysis determined that the TCR J delta 1 gene fragment of the involved chromosome was relocated approximately 280 kb downstream of the c-myc proto-oncogene locus found on chromosome band 8q24. This rearrangement was reminiscent of the Burkitt's lymphoma variants that translocate to a region identified as the pvt-1 locus. Sequence comparison of the breakpoint junctions of interchromosomal rearrangements in T-cell leukemias involving the TCR delta-chain locus revealed novel signal-like sequence motifs, GCAGA(A/T)C and CCCA(C/G)GAC. These sequences were found on chromosome 8 at the 5' flanking site of the breakpoint junction of chromosome 8 in the TCR gamma/delta leukemic cells reported here and also on chromosome 1 in T-cell acute lymphocytic leukemia patients carrying the t(1;14)(p32;q11) rearrangement. These results suggest that (i) during early stages of gamma delta T-cell ontogeny, the region 280 kb 3' of the c-myc proto-oncogene on chromosome 8 is fragile and accessible to the lymphoid recombination machinery and (ii) rearrangements to both 8q24 and 1p32 may be governed by novel sequence motifs and be subject to common enzymatic mechanisms. Images PMID:1406658

  11. Deceased tissue donor serology and molecular testing for HIV, hepatitis B and hepatitis C viruses: a lack of cadaveric validated tests.

    PubMed

    Victer, Thayssa Neiva da Fonseca; Dos Santos, Cris Stéphany Rodrigues; Báo, Sônia Nair; Sampaio, Thatiane Lima

    2016-12-01

    Vital to patient safety is the accurate assessment and minimization of risk for human immunodeficiency virus (HIV), Hepatitis C (HCV), and Hepatitis B (HBV) virus transmission by deceased donor organ and tissue transplantation. The pathogens are tested by serological kits based on enzyme-linked immunosorbent assay (ELISA), chemiluminescence (CLIA) and eletrochemiluminescence (ECLIA) immunoassays. Organ transplantation is a highly successful life-saving treatment in Brazil, but the Brazilian Health Surveillance Agency currently mandates that all deceased organ donors are screened for HIV, HCV and HBV following living donor policies. In this review, six ELISA (Wama(®), Bio-Rad(®), Biomerieux(®), DiaSorin(®), Acon Biotech(®) and Biokit(®)), three CLIA (Abbott(®), Siemens(®), Diasorin(®)) and one ECLIA (Roche(®)) were utilized for evaluating the effectiveness of those serological tests for deceased donors in Brazil according to manufacturer's guidelines. NAT for HIV, HCV and HBV can assist with detection of pre-seroconversion for those infections, and only Cobas(®) TaqScreen MPX(®) test, the Tigris System(®) Procleix Ultrio Assay(®) and the Bio-Manguinhos(®) HIV/HCV/HBV NAT are commercially available. Between all the tests, only the manufacturer Abbott(®) and Cobas(®) TaqScreen MPX(®) test are currently validated for cadaver samples.

  12. The Delta 2 launcher

    NASA Astrophysics Data System (ADS)

    Ousley, Gilbert W., Sr.

    1991-12-01

    The utilization of the Delta 2 as the vehicle for launching Aristoteles into its near Sun synchronous orbit is addressed. Delta is NASA's most reliable launch vehicle and is well suited for placing the present Aristoteles spacecraft into a 400 m circular orbit. A summary of some of the Delta 2 flight parameters is presented. Diagrams of a typical Delta 2 two stage separation are included along with statistics on delta reliability and launch plans.

  13. Hepatitis C

    MedlinePlus

    ... your doctor may want you to get the hepatitis B vaccine (and maybe the hepatitis A vaccine, too), if you don't already have these viruses. If you have hepatitis C, you are more likely to catch hepatitis A or hepatitis B, which would cause more damage to your liver. ...

  14. Hepatitis C

    MedlinePlus

    Hepatitis C Overview By Mayo Clinic Staff Hepatitis C is a viral infection that causes liver inflammation, sometimes leading to serious liver damage. The hepatitis C virus (HCV) spreads through contaminated ...

  15. Toxic Hepatitis

    MedlinePlus

    Toxic hepatitis Overview By Mayo Clinic Staff Toxic hepatitis is an inflammation of your liver in reaction to certain substances to which you're exposed. Toxic hepatitis can be caused by alcohol, chemicals, drugs or ...

  16. delta-Hexachlorocyclohexane (delta-HCH)

    Integrated Risk Information System (IRIS)

    delta - Hexachlorocyclohexane ( delta - HCH ) ; CASRN 319 - 86 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Ass

  17. [Prevention of virus hepatitis A to E].

    PubMed

    Cornberg, M; Manns, M P

    2011-03-01

    Infection with hepatitis viruses can lead to acute hepatitis with the risk of developing liver failure. Chronic viral hepatitis may evolve into liver cirrhosis and hepatocellular carcinoma. Thus, prevention of viral hepatitis and its sequels is essential. Vaccination against hepatitis A is successful in almost all individuals. Protective antibodies maintain for at least 20 years. Booster vaccinations are not necessary. Since the introduction of hepatitis A vaccines, the incidence of new HAV-infections has declined significantly. Hepatitis B vaccines are safe and highly effective. Special populations such as dialysis patients or immunocompromised patients require special vaccine schedules. New vaccines with improved adjuvants are currently being tested in clinical trials. So far there is no hepatitis C vaccine on the horizon. Prophylaxis of HCV-infections relies primarily on hygiene measures. Early therapy of acute hepatitis C can prevent chronic hepatitis C. HDV-infection can only be established if HBsAg is present. Thus, prevention of hepatitis B or elimination of HBsAg means prevention of hepatitis delta. Hepatitis E vaccines have been evaluated in phase III studies. The development of HEV vaccines becomes more relevant since chronic HEV infections have been reported in immunosuppressed individuals.

  18. The delta opioid receptor tool box.

    PubMed

    Vicente-Sanchez, Ana; Segura, Laura; Pradhan, Amynah A

    2016-12-03

    In recent years, the delta opioid receptor has attracted increasing interest as a target for the treatment of chronic pain and emotional disorders. Due to their therapeutic potential, numerous tools have been developed to study the delta opioid receptor from both a molecular and a functional perspective. This review summarizes the most commonly available tools, with an emphasis on their use and limitations. Here, we describe (1) the cell-based assays used to study the delta opioid receptor. (2) The features of several delta opioid receptor ligands, including peptide and non-peptide drugs. (3) The existing approaches to detect delta opioid receptors in fixed tissue, and debates that surround these techniques. (4) Behavioral assays used to study the in vivo effects of delta opioid receptor agonists; including locomotor stimulation and convulsions that are induced by some ligands, but not others. (5) The characterization of genetically modified mice used specifically to study the delta opioid receptor. Overall, this review aims to provide a guideline for the use of these tools with the final goal of increasing our understanding of delta opioid receptor physiology.

  19. Epidemiology and Molecular Characterization of Hepatitis B Virus Infection in Isolated Villages in the Western Brazilian Amazon

    PubMed Central

    Castilho, Márcia da Costa; Costa de Oliveira, Cintia Mara; Gimaque, João Bosco de Lima; Leão, Jorge Di Tommaso; Braga, Wornei Silva Miranda

    2012-01-01

    Individuals from three isolated, rural communities in the western Brazilian Amazon were evaluated for serological markers of hepatitis B virus (HBV) infection, HBV genotype, and the presence of risk factors for infection and transmission. Of the 225 individuals studied, 79.1% had serological evidence of HBV infection; 10.2% individuals were chronic carriers for HBV surface antigen (HBsAg-positive). Analysis of risk factors indicates that HBV is transmitted mainly horizontally within the family from a chronic “active” carrier for hepatitis B “e” antigen (HBeAg-positive), though a strong possibility of vertical transmission remains. The predominance of HBV genotype F, with a higher genomic similarity between the isolates, indicated a relatively recent introduction of HBV, from a common source, to the area. This study sheds light on the HBV epidemiology in the Brazilian Amazon region and highlights the need for greater emphasis on HBV control and immunization programs. PMID:22908032

  20. Hepatitis B and HIV

    MedlinePlus

    ... Problems : Hepatitis B Subscribe Translate Text Size Print Hepatitis B What is Hepatitis? Hepatitis means inflammation of the liver. This condition ... our related pages, Hepatitis A and Hepatitis C . Hepatitis B and HIV About 10% of people living ...

  1. Hepatitis A

    MedlinePlus

    ... transaminase enzyme levels Treatment There is no specific treatment for hepatitis A. You should rest when the symptoms are ... and have not had hepatitis A or the hepatitis A vaccine. Common reasons for getting one or both of these treatments include: You live with someone who has hepatitis ...

  2. [Recent acquisitions on viral hepatitis].

    PubMed

    Resti, M; Tucci, F; Vierucci, A

    1990-01-01

    In the last years the research on viral hepatitis let to better understand the biological, molecular, immunological and epidemiologic characteristics of the viruses that are responsible for hepatitis. The first studied virus was hepatitis B virus (HBv). The scientific attention is still, today, focused on that virus since new markers of infectivity and biological importance in early diagnosis and in disease evolution have been found. The most important result in the last years in the field of viral hepatitis has been, however, the identification of agents responsible for Non-A-Non-B hepatitis. Its epidemiology and clinical importance are discussed in the present paper. Virus C is the most important parenteral agent of NANB hepatitis. Its epidemiology in at risk populations and its role in post-transfusional and cryptogenetic hepatitis are here discussed. The research of new markers of HCV infection is today considered a main goal since the role of the only marker now available is still under discussion.

  3. Treatment with oligonol, a low-molecular polyphenol derived from lychee fruit, attenuates diabetes-induced hepatic damage through regulation of oxidative stress and lipid metabolism.

    PubMed

    Noh, Jeong Sook; Park, Chan Hum; Yokozawa, Takako

    2011-10-01

    We have identified the effects of oligonol, a low-molecular polyphenol derived from lychee fruit, on oxidative stress and lipid metabolism in a type 2 diabetic model. Oligonol was orally administered at 10 or 20 mg per kg body weight per d for 8 weeks to db/db mice, and its effects were compared with those of the vehicle in db/db and m/m mice. Serum and hepatic biochemical factors, and protein and mRNA expression related to lipid metabolism were measured. In the oligonol-administered group, there were significant reductions of reactive oxygen species (ROS), lipid peroxidation, and the TAG and total cholesterol concentrations in both the serum and liver. Additionally, oligonol attenuated oxidative stress through the inhibition of advanced glycation endproduct formation and its receptor expression. Furthermore, augmented expressions of NF-κBp65 and inducible NO synthase were down-regulated to the levels of m/m mice in the group treated with oligonol at 20 mg/kg. Regarding lipid metabolism, lower hepatic lipid resulted from the down-regulation of sterol regulatory element-binding protein-1 and its target gene of lipogenic enzymes in the liver of db/db mice. The present results suggest that oligonol has protective effects against ROS-related inflammation and excess lipid deposition in the type 2 diabetic liver.

  4. Molecular analysis of hepatitis B virus (HBV) in an HIV co-infected patient with reactivation of occult HBV infection following discontinuation of lamivudine-including antiretroviral therapy

    PubMed Central

    2011-01-01

    Background Occult hepatitis B virus (HBV) infection (OBI) is characterized by HBV DNA persistence even though the pattern of serological markers indicates an otherwise resolved HBV infection. Although OBI is usually clinically silent, immunocompromised patients may experience reactivation of the liver disease. Case presentation We report the case of an individual with human immunodeficiency virus (HIV) infection and anti-HBV core antibody positivity, who experienced severe HBV reactivation after discontinuation of lamivudine-including antiretroviral therapy (ART). HBV sequencing analysis showed a hepatitis B surface antigen escape mutant whose presence in an earlier sample excluded reinfection. Molecular sequencing showed some differences between two isolates collected at a 9-year interval, indicating HBV evolution. Resumption of ART containing an emtricitabine/tenofovir combination allowed control of plasma HBV DNA, which fell to undetectable levels. Conclusion This case stresses the ability of HBV to evolve continuously, even during occult infection, and the effectiveness of ART in controlling OBI reactivation in HIV-infected individuals. PMID:22054111

  5. A virus resonance light scattering sensor based on mussel-inspired molecularly imprinted polymers for high sensitive and high selective detection of Hepatitis A Virus.

    PubMed

    Yang, Bin; Gong, Hang; Chen, Chunyan; Chen, Xiaoming; Cai, Changqun

    2017-01-15

    We described a novel resonance light scattering (RLS) sensor for the specific recognition of trace quantities of Hepatitis A Virus (HAV); the sensor was based on a mussel-inspired hepatitis molecularly imprinted polymer. As a recognition element, polydopamine (PDA)-coated totivirus-imprinted polymer was introduced on the surface of SiO2 nanoparticles (virus-imprinted SiO2@PDA NPs) using an efficient one-step synthesis method. The target virus was selectively captured by the imprinted polymer films, thereby increasing the RLS intensity. A simple fluorescence spectrophotometer was employed to measure the changes in the intensity. The enhanced RLS intensity (∆IRLS) was proportional to the concentration of HAV in the range of 0.04-6.0nmol∙L(-1), with a low limit of detection of 8.6pmol∙L(-1). The selectivity study confirmed that the resultant HAV-imprinted SiO2@PDA NPs possessed high selectivity for HAV. The sensor was successfully applied for the direct detection of additional HAV from a 20,000-fold dilution of human serum. The proposed strategy is simple, eco-friendly, highly selective, and sensitive.

  6. Deletion of the collagen-specific molecular chaperone Hsp47 causes endoplasmic reticulum stress-mediated apoptosis of hepatic stellate cells.

    PubMed

    Kawasaki, Kunito; Ushioda, Ryo; Ito, Shinya; Ikeda, Kazuo; Masago, Yusaku; Nagata, Kazuhiro

    2015-02-06

    Chronic liver injury, often caused by alcoholism and viral hepatitis, causes liver fibrosis via the induction of collagen production. In liver fibrosis, hepatic stellate cells (HSCs) are activated and transform into myofibroblasts, which actively produce and secrete collagen into the extracellular matrix. Hsp47 (heat shock protein 47) is a collagen-specific molecular chaperone that is essential for the maturation and secretion of collagen. Here, we used the Cre-LoxP system to disrupt the Hsp47 gene in isolated HSCs from Hsp47 floxed mice. Immature type I procollagen accumulated and partially aggregated in Hsp47-KO HSCs. This accumulation was augmented when autophagy was inhibited, which induced expression of the endoplasmic reticulum (ER) stress-inducible proteins BiP (immunoglobulin heavy chain-binding protein) and Grp94 (94-kDa glucose-regulated protein). The inhibition of autophagy in Hsp47-KO HSCs also induced CHOP (CCAAT/enhancer-binding protein homologous protein), which is an ER stress-induced transcription factor responsible for apoptosis. These data suggest that apoptosis is induced through ER stress by procollagen accumulation in Hsp47-KO HSCs when autophagy is inhibited. Thus, Hsp47 could be a promising therapeutic target in liver fibrosis.

  7. Multicentre study of prevalence of HBV-associated delta infection and liver disease in drug-addicts.

    PubMed

    Raimondo, G; Smedile, A; Gallo, L; Balbo, A; Ponzetto, A; Rizzetto, M

    1982-01-30

    To assess the epidemiological and pathogenic effects of infection with the hepatitis-B-virus (HBV)-associated delta agent in addicts who take drugs parenterally, 225 symptomless addicts from Italy and 261 addicts with HBsAg-positive hepatitis from Italy, Denmark, Switzerland, and Ireland were tested for delta antigen (delta-Ag) and its antibody (anti-delta) by radioimmunoassay. 79 liver biopsy specimens from HBsAg-positive addicts were also tested for intrahepatic delta-Ag by immunofluorescence. Anti-delta was found in 9 (27%) of 33 of the symptomless HBsAg-positive addicts, in 13 (8%) of 156 of those without HBsAg but with anti-HBs, and in none of those negative for HBV markers. The prevalence of serum delta-Ag or anti-delta among addicts with HBsAg-positive hepatitis was 64% (104/161) in Italy, 44% (8/18) in Denmark, 33% (11/33) in Switzerland, and 31% (15/49) in Ireland. 32 of the 79 (40%)liver biopsy specimens from HBsAg-positive addicts showed positive delta-Ag immunofluorescence. Delta infection occurring simultaneously with HBV infection is common and possibly a major cause of liver disease in drug addicts who receive drug parenterally. The spread of delta infection in drug-using communities is not confined to one country, and the drug habit may represent the major means by which delta agent spreads in areas of the Western world where this infection is not endemic.

  8. Virtual screening of natural inhibitors to the predicted HBx protein structure of Hepatitis B Virus using molecular docking for identification of potential lead molecules for liver cancer

    PubMed Central

    Pathak, Rajesh Kumar; Baunthiyal, Mamta; Taj, Gohar; Kumar, Anil

    2014-01-01

    The HBx protein in Hepatitis B Virus (HBV) is a potential target for anti-liver cancer molecules. Therefore, it is of interest to screen known natural compounds against the HBx protein using molecular docking. However, the structure of HBx is not yet known. Therefore, the predicted structure of HBx using threading in LOMET was used for docking against plant derived natural compounds (curcumin, oleanolic acid, resveratrol, bilobetin, luteoline, ellagic acid, betulinic acid and rutin) by Molegro Virtual Docker. The screening identified rutin with binding energy of -161.65 Kcal/mol. Thus, twenty derivatives of rutin were further designed and screened against HBx. These in silico experiments identified compounds rutin01 (-163.16 Kcal/mol) and rutin08 (- 165.76 Kcal/mol) for further consideration and downstream validation. PMID:25187683

  9. Molecular characterization of hepatitis A outbreak in the province of Rome, Lazio region, Italy, January-July 2013.

    PubMed

    Capobianchi, Maria R; Garbuglia, Anna Rosa; Agrati, Chiara; Rianda, Alessia; Noto, Pasquale; Corpolongo, Angela; Cataldo, Maria Adriana; Rosati, Silvia; Zaccaro, Paola; Loffredo, Mariarosaria; Pompa, Maria Grazia; Girardi, Enrico; Scognamiglio, Paola; Ippolito, Giuseppe

    2014-04-01

    Reduced circulation of hepatitis A virus lead to an increase of susceptible individuals, and outbreaks occurred recently. In Northern Italy an outbreak is ongoing, attributed to a monophyletic genotype IA strain, with mixed frozen berries as probable source. From 01/01/2013 to 07/15/2013, 30 cases were diagnosed at National Institute for Infectious Diseases, Rome, Italy, representing about twice the number of cases in whole 2012. Phylogenetic analysis indicated that most, although not all, infections were attributable to the same monophyletic genotype IA strain identified in the contemporary Northern Italy outbreak. This strain is also very similar to previous isolates from Venezuela.

  10. A photoelectron-photoion coincidence imaging apparatus for femtosecond time-resolved molecular dynamics with electron time-of-flight resolution of {sigma}=18 ps and energy resolution {delta}E/E=3.5%

    SciTech Connect

    Vredenborg, Arno; Roeterdink, Wim G.; Janssen, Maurice H. M.

    2008-06-15

    We report on the construction and performance of a novel photoelectron-photoion coincidence machine in our laboratory in Amsterdam to measure the full three-dimensional momentum distribution of correlated electrons and ions in femtosecond time-resolved molecular beam experiments. We implemented sets of open electron and ion lenses to time stretch and velocity map the charged particles. Time switched voltages are operated on the particle lenses to enable optimal electric field strengths for velocity map focusing conditions of electrons and ions separately. The position and time sensitive detectors employ microchannel plates (MCPs) in front of delay line detectors. A special effort was made to obtain the time-of-flight (TOF) of the electrons at high temporal resolution using small pore (5 {mu}m) MCPs and implementing fast timing electronics. We measured the TOF distribution of the electrons under our typical coincidence field strengths with a temporal resolution down to {sigma}=18 ps. We observed that our electron coincidence detector has a timing resolution better than {sigma}=16 ps, which is mainly determined by the residual transit time spread of the MCPs. The typical electron energy resolution appears to be nearly laser bandwidth limited with a relative resolution of {delta}E{sub FWHM}/E=3.5% for electrons with kinetic energy near 2 eV. The mass resolution of the ion detector for ions measured in coincidence with electrons is about {delta}m{sub FWHM}/m=1/4150. The velocity map focusing of our extended source volume of particles, due to the overlap of the molecular beam with the laser beams, results in a parent ion spot on our detector focused down to {sigma}=115 {mu}m.

  11. Hepatitis virus C infection, adipokines and hepatic steato-fibrosis.

    PubMed

    Ciurtin, Coziana; Stoica, Victor

    2008-01-01

    Hepatitis C viral infection is accompanied by various serum alterations that could explain its molecular impact on hepatic structure and metabolic homeostasis. Recently it has been shown that adipocytokines play a pivotal role in development of hepatic steato-fibrosis, different studies giving a support of the hypothesis that the balance of adipocytokine expression is a key regulator for the progression of hepatic steatosis and fibrosis. The association between insulin resistance and hepatitis C virus genotypes and liver fibrosis stage foreshadowed that virus-induced insulin resistance may be a mechanism for fibrogenesis in chronic hepatitis C virus infection. The main importance of adipocytokine profile detection consists in the prediction of steatosis induction that has clinical relevance, being associated with advanced fibrosis and hyporesponsiveness to antiviral therapy.

  12. HEPATITIS VIRUS C INFECTION, ADIPOKINES AND HEPATIC STEATO–FIBROSIS

    PubMed Central

    Ciurtin, C

    2008-01-01

    Hepatitis C viral infection is accompanied by various serum alterations that could explain its molecular impact on hepatic structure and metabolic homeostasis. Recently it has been shown that adipocytokines play a pivotal role in development of hepatic steato–fibrosis, different studies giving a support of the hypothesis that the balance of adipocytokine expression is a key regulator for the progression of hepatic steatosis and fibrosis. The association between insulin resistance and hepatitis C virus genotypes and liver fibrosis stage foreshadowed that virus–induced insulin resistance may be a mechanism for fibrogenesis in chronic hepatitis C virus infection. The main importance of adipocytokine profile detection consists in the prediction of steatosis induction that has clinical relevance, being associated with advanced fibrosis and hyporesponsiveness to antiviral therapy. PMID:20108479

  13. Hepatitis C: Treatment

    MedlinePlus

    ... 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 ...

  14. Hepatitis A

    MedlinePlus

    ... an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... washed in untreated water Putting into your mouth a finger or object that came into contact with ...

  15. Hepatitis B

    MedlinePlus

    ... commonly used with viral hepatitis and related conditions. Web Resources American Liver Foundation A national nonprofit organization ... other liver diseases through research, education, and advocacy. Web site features a database directory of hepatitis clinical ...

  16. Hepatitis B

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000279.htm Hepatitis B To use the sharing features on this page, please enable JavaScript. Hepatitis B is irritation and swelling (inflammation) of the ...

  17. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  18. Hepatitis B

    MedlinePlus

    ... times more infectious than HIV. Which adults need hepatitis B vaccine? Any sexually active adult who is not in ... share needles, syringes, or other drug-injection equipment. Hepatitis B vaccine is available alone or in a combination with ...

  19. Molecular simulations illuminate the role of regulatory components of the RNA polymerase from the hepatitis C virus in influencing protein structure and dynamics.

    PubMed

    Davis, Brittny C; Thorpe, Ian F

    2013-07-02

    The RNA polymerase (gene product NS5B) from the hepatitis C virus is responsible for replication of the viral genome and is a validated drug target for new therapeutic agents. NS5B has a structure resembling an open right hand (containing the fingers, palm, and thumb subdomains), a hydrophobic C-terminal region, and two magnesium ions coordinated in the palm domain. Biochemical data suggest that the magnesium ions provide structural stability and are directly involved in catalysis, while the C-terminus plays a regulatory role in NS5B function. Nevertheless, the molecular mechanisms by which these two features regulate polymerase activity remain unclear. To answer this question, we performed molecular dynamics simulations of NS5B variants with different C-terminal lengths in the presence or absence of magnesium ions to determine the impact on enzyme properties. We observed that metal binding increases both the magnitude and the degree of correlated enzyme motions. In contrast, we observed that the C-terminus restricts enzyme dynamics. Under certain conditions, our simulations revealed a fully closed conformation of NS5B that may facilitate de novo initiation of RNA replication. This knowledge is important because it fosters the development of a comprehensive description of RNA replication by NS5B and is relevant to understanding the functional properties of a broad class of related RNA polymerases such as 3D-pol from poliovirus. Ultimately, this information may also be pertinent to designing novel NS5B therapeutics.

  20. Molecular characterization of hepatitis B virus in blood donors from Burkina Faso: Prevalence of quasi-subgenotype A3, genotype E, and mixed infections.

    PubMed

    Candotti, Daniel; Diarra, Birama; Bisseye, Cyrille; Tao, Issoufou; Pham Quang, Kei; Sanou, Mahamoudou; Laperche, Syria; Sanogo, Rokia; Allain, Jean-Pierre; Simpore, Jacques

    2016-12-01

    Burkina Faso is a highly endemic area for Hepatitis B virus (HBV) which remains a major challenge for blood safety with >13% of candidate blood donors being chronically infected. However, little is known about the molecular epidemiology of the viral strains currently circulating. In this study, 99 HBV strains from HBsAg positive candidate blood donors in Ougadougou were genetically characterized by sequencing the pre-S/S region of the viral genome. Phylogenetic analyses revealed a 25% prevalence of HBV quasi-subgenotype A3 (A3QS ) co-circulating with the confirmed dominant HBV genotype E (72%). HBV/A3QS sequences formed a sub-cluster closely related to West-African sequences previously characterized, and showed a low intra-group genetic diversity (0.75%) suggesting a relatively recent spreading of HBV/A3QS strains in Burkina Faso. Low genetic diversity of genotype E strains compared to A3QS was confirmed. Mixed infections with the two genotypes were identified in 3% of the donors tested and contributed to artifacts during PCR amplification of the viral genome leading to erroneous apparent intergenotype recombinant sequences. While the co-circulation of two HBV genotypes in a restricted area may favor the emergence of intergenotype recombinant variants, strictly controlled molecular experimental procedures should be used to accurately characterize HBV circulating recombinant forms. J. Med. Virol. 88:2145-2156, 2016. © 2016 Wiley Periodicals, Inc.

  1. Diagnosis of hepatitis B

    PubMed Central

    Song, Jeong Eun

    2016-01-01

    Hepatitis B virus (HBV) infection is a major global health problems leading to severe liver disease such as cirrhosis and hepatocellular carcinoma (HCC). HBV is a circular, partly double-stranded DNA virus with various serological markers: hepatitis B surface antigen (HBsAg) and anti-HBs, anti-HBc IgM and IgG, and hepatitis B e antigen (HBeAg) and anti-HBe. It is transmitted by sexual, parenteral and vertical route. One significant method to diminish the burden of this disease is timely diagnosis of acute, chronic and occult cases of HBV. First step of HBV diagnosis is achieved by using serological markers for detecting antigens and antibodies. In order to verify first step of diagnosis, to quantify viral load and to identify genotypes, quantitative or qualitative molecular tests are used. In this article, the serological and molecular tests for diagnosis of HBV infection will be reviewed. PMID:27761442

  2. Hepatitis C

    MedlinePlus

    ... 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 ...

  3. Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) presenting with acute fulminant hepatic failure.

    PubMed

    Mhanni, A A; Chan, A; Collison, M; Seifert, B; Lehotay, D C; Sokoro, Ah; Huynh, H Q; Greenberg, C R

    2008-03-01

    We report on two Aboriginal patients with the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome. Both presented with acute hepatic failure with severe hypertransaminasemia and coagulopathy, prompting evaluation for emergent liver transplantation. The diagnosis of HHH syndrome was based on the presence of typical metabolic abnormalities. A protein-restricted diet and L-arginine or L-citrulline supplementation were immediately started, with rapid normalization of liver function test results and other biochemical abnormalities. Molecular analysis of the SLC25A15 gene showed that the two patients were homozygous for the common French Canadian mutation (F188Delta). The diagnosis of HHH syndrome should be considered in patients with unexplained fulminant hepatic failure. There does not appear to be a genotype-phenotype correlation for this presentation, inasmuch as the only other reported patient presenting with this picture had two different point mutations. Early identification and prompt treatment of these patients is crucial to avoid liver transplantation and can be life saving.

  4. Molecular basis for the direct inhibition of AP-1 DNA binding by 15-deoxy-Delta 12,14-prostaglandin J2.

    PubMed

    Pérez-Sala, Dolores; Cernuda-Morollón, Eva; Cañada, F Javier

    2003-12-19

    Cyclopentenone prostaglandins may interfere with cellular functions by multiple mechanisms. The cyclopentenone 15-deoxy-Delta 12,14-prostaglandin J2 (15d-PGJ2) has been reported to inhibit the activity of the transcription factor AP-1 in several experimental settings. We have explored the possibility of a direct interaction of 15d-PGJ2 with AP-1 proteins. Here we show that 15d-PGJ2 covalently modifies c-Jun and directly inhibits the DNA binding activity of AP-1. The modification of c-Jun occurs both in vitro and in intact cells as detected by labeling with biotinylated 15d-PGJ2 and mass spectrometry analysis. Attachment of the cyclopentenone prostaglandin occurs at cysteine 269, which is located in the c-Jun DNA binding domain. In addition, 15d-PGJ2 can promote the oligomerization of a fraction of c-Jun through the formation of intermolecular disulfide bonds or 15d-PGJ2-bonded dimers. Our results identify a novel site of interaction of 15d-PGJ2 with the AP-1 activation pathway that may contribute to the complex effects of cyclopentenone prostaglandins on the cellular response to pro-inflammatory agents. They also show the first evidence for the induction of protein cross-linking by 15d-PGJ2.

  5. Experimental and molecular docking studies on DNA binding interaction of adefovir dipivoxil: Advances toward treatment of hepatitis B virus infections

    NASA Astrophysics Data System (ADS)

    Shahabadi, Nahid; Falsafi, Monireh

    The toxic interaction of adefovir dipivoxil with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multi-spectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove binding mode. The binding constant of UV-visible and the number of binding sites were 3.33 ± 0.2 × 104 L mol-1and 0.99, respectively. The fluorimetric studies showed that the reaction between the drug and CT-DNA is exothermic (ΔH = 34.4 kJ mol-1; ΔS = 184.32 J mol-1 K-1). Circular dichroism spectroscopy (CD) was employed to measure the conformational change of CT-DNA in the presence of adefovir dipivoxil, which verified the groove binding mode. Furthermore, the drug induces detectable changes in its viscosity. The molecular modeling results illustrated that adefovir strongly binds to groove of DNA by relative binding energy of docked structure -16.83 kJ mol-1. This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the toxic interaction of small molecular pollutants and drugs with bio macromolecules, which contributes to clarify the molecular mechanism of toxicity or side effect in vivo.

  6. Pen Branch delta expansion

    SciTech Connect

    Nelson, E.A.; Christensen, E.J.; Mackey, H.E.; Sharitz, R.R.; Jensen, J.R.; Hodgson, M.E.

    1984-02-01

    Since 1954, cooling water discharges from K Reactor ({anti X} = 370 cfs {at} 59 C) to Pen Branch have altered vegetation and deposited sediment in the Savannah River Swamp forming the Pen Branch delta. Currently, the delta covers over 300 acres and continues to expand at a rate of about 16 acres/yr. Examination of delta expansion can provide important information on environmental impacts to wetlands exposed to elevated temperature and flow conditions. To assess the current status and predict future expansion of the Pen Branch delta, historic aerial photographs were analyzed using both basic photo interpretation and computer techniques to provide the following information: (1) past and current expansion rates; (2) location and changes of impacted areas; (3) total acreage presently affected. Delta acreage changes were then compared to historic reactor discharge temperature and flow data to see if expansion rate variations could be related to reactor operations.

  7. Viral hepatitis in hemodialysis: An update

    PubMed Central

    Bernieh, Bassam

    2015-01-01

    Hepatitis outbreaks in hemodialysis (HD) patients and staff were reported in the late 1960s, and a number of hepatotropic viruses transmitted by blood and other body fluids have been identified. Hepatitis B virus (HBV) was the first significant hepatotropic virus to be identified in HD centers. HBV infection has been effectively controlled by active vaccination, screening of blood donors, the use of erythropoietin and segregation of HBV carriers. Hepatitis delta virus is a defective virus that can only infect HBV-positive individuals. Hepatitis C virus (HCV) is the most significant cause of non-A, non-B hepatitis and is mainly transmitted by blood transfusion. The introduction in 1990 of routine screening of blood donors for HCV contributed significantly to the control of HCV transmission. An effective HCV vaccine remains an unsolved challenge; however, pegylation of interferon-alfa has made it possible to treat HCV-positive dialysis patients. Unexplained sporadic outbreaks of hepatitis by the mid-1990s prompted the discovery of hepatitis G virus, hepatitis GB virus C and the TT virus. The vigilant observation of guidelines on universal precaution and regular virologic testing are the cornerstones of the effective control of chronic hepatitis in the setting of HD. Major recent advances in the viral diagnosis technology and the development of new oral, direct-acting antiviral agents allow early diagnosis and better therapeutic response. The current update will review the recent developments, controversies and new treatment of viral hepatitis in HD patients. PMID:27847896

  8. An Effective Molecular Target Site in Hepatitis B Virus S Gene for Cas9 Cleavage and Mutational Inactivation

    PubMed Central

    Li, Hao; Sheng, Chunyu; Liu, Hongbo; Liu, Guangze; Du, Xinying; Du, Juan; Zhan, Linsheng; Li, Peng; Yang, Chaojie; Qi, Lihua; Wang, Jian; Yang, Xiaoxia; Jia, Leili; Xie, Jing; Wang, Ligui; Hao, Rongzhang; Xu, Dongping; Tong, Yigang; Zhou, Yusen; Zhou, Jianjun; Sun, Yansong; Li, Qiao; Qiu, Shaofu; Song, Hongbin

    2016-01-01

    Chronic hepatitis B infection remains incurable because HBV cccDNA can persist indefinitely in patients recovering from acute HBV infection. Given the incidence of HBV infection and the shortcomings of current therapeutic options, a novel antiviral strategy is urgently needed. To inactivate HBV replication and destroy the HBV genome, we employed genome editing tool CRISPR/Cas9. Specifically, we found a CRISPR/Cas9 system (gRNA-S4) that effectively targeted the HBsAg region and could suppress efficiently viral replication with minimal off-target effects and impact on cell viability. The mutation mediated by CRISPR/Cas9 in HBV DNA both in a stable HBV-producing cell line and in HBV transgenic mice had been confirmed and evaluated using deep sequencing. In addition, we demonstrated the reduction of HBV replication was caused by the mutation of S4 site through three S4 region-mutated monoclonal cells. Besides, the gRNA-S4 system could also reduce serum surface-antigen levels by 99.91 ± 0.05% and lowered serum HBV DNA level below the negative threshold in the HBV hydrodynamics mouse model. Together, these findings indicate that the S4 region may be an ideal target for the development of innovative therapies against HBV infection using CRISPR/Cas9. PMID:27570484

  9. Molecular characterization of woodchuck IFI16 and AIM2 and their expression in woodchucks infected with woodchuck hepatitis virus (WHV)

    PubMed Central

    Yan, Qi; Li, Mengmeng; Liu, Qin; Li, Fanghui; Zhu, Bin; Wang, Junzhong; Lu, Yinping; Liu, Jia; Wu, Jun; Zheng, Xin; Lu, Mengji; Wang, Baoju; Yang, Dongliang

    2016-01-01

    IFI16 and AIM2 are important DNA sensors in antiviral immunity. To characterize these two molecules in a woodchuck model, which is widely used to study hepatitis B virus (HBV) infection, we cloned and analyzed the complete coding sequences (CDSs) of woodchuck IFI16 and AIM2, and found that AIM2 was highly conserved in mammals, whereas the degree of sequence identity between woodchuck IFI16 and its mammalian orthologues was low. IFI16 and IFN-β were upregulated following VACV ds 70 mer transfection, while AIM2 and IL-1β were upregulated following poly (dA:dT) transfection, both in vitro and in vivo; IFI16-targeted siRNA decreased the transcription of IFI16 and IFN-β stimulated by VACV ds 70 mer, and AIM2 siRNA interference downregulated AIM2 and IL-1β transcripts stimulated by poly (dA:dT), in vitro, suggesting that woodchuck IFI16 and AIM2 may play pivotal roles in the DNA-mediated induction of IFN-β and IL-1β, respectively. IFI16 and AIM2 transcripts were upregulated in the liver and spleen following acute WHV infection, while IFI16 was downregulated in the liver following chronic infection, implying that IFI16 and AIM2 may be involved in WHV infection. These data provide the basis for the study of IFI16- and AIM2-mediated innate immunity using the woodchuck model. PMID:27354260

  10. Molecular characterization of hepatitis A virus isolates from Goiânia, Gioás, Brazil.

    PubMed

    Fiaccadori, Fabíola Souza; Pereira, Maristela; Coelho, Alexandre Siqueira Guedes; Borges, Ana Maria Tavares; Parente, Juliana Alves; Soares, Célia Maria de Almeida; Cardoso, Divina das Dôres de Paula

    2008-12-01

    Hepatitis A virus (HAV) infection is a public health problem worldwide and the virus has been classified into six genotypes. In Brazil, the only genotype that has been found is genotype I, predominately from subgenotype IA. Here, the HAV genotypes were analyzed of 18 isolates circulating between 1996-2001 in Goiânia, state of Goiás, Brazil. Viral RNA was extracted from 18 serum samples and amplified (RT-PCR/nested-PCR), followed by the genomic sequencing of the VP1/2A junction region of the HAV genome. Sequences of 168 nucleotides were compared and analyzed using the BLAST N, Clustal X and PAUP v. 4.10b programs. All samples were classified as genotype I, with 10 belonging to subgenotype IA and eight to subgenotype IB. The subgenotype IA isolates showed greater diversity than the subgenotype IB isolates at the nucleotide level. Elevated identity values were found between isolates obtained in this study and those from other regions of the world, including Brazil, highlighting the high conservation among different isolates of this virus. However, changes in the HAV subgenotype circulation could also be observed during the evaluated period.

  11. Evaluation of in-house and commercial genotyping assays for molecular typing of hepatitis C virus in Hong Kong.

    PubMed

    Lam, T H J; Cheng, R S; Lai, S T; Tsang, T Y; Cheng, V C C; Ho, S L; Yam, W C

    2010-01-01

    This study aims to evaluate genotyping assays for hepatitis C virus (HCV). An in-house nucleic acid sequencing method is performed in parallel with the Roche Linear Array HCV genotyping test on 73 HCV-positive (66 clinical samples and seven proficiency testing quality control samples) and 12 HCV-negative samples (11 clinical samples and one proficiency testing sample). The performance of the in-house method was comparable with that of the Roche assay (concordance rate: 89.4%). Discordant results included four mixed infections missed by the in-house method, two false-negatives with the Roche assay, and three discrepant results. The in-house method exhibited a higher resolution (subtype vs. genotype level) at a lower running cost (25% of the commercial assay). The in-house method was also used to genotype 375 HCV clinical isolates to determine the genotypic distribution of HCV in Hong Kong between 2005 and 2008. A total of 441 (52.8%) clinical isolates proved to be genotype 1, which shows a poorer response to interferon therapy. Genotype 6 was the next most common (32.0%). Prevalence of genotypes 2 and 3 was 7.7% and 6.6%, respectively, and prevalence of genotypes 4 and 5 was 0.9% and 0%, respectively. Although the in-house nucleic acid sequencing method failed to detect a few cases of mixed HCV infection, its high resolution and low running cost make it suitable for surveillance and outbreak investigation.

  12. Molecular Mechanisms of Viral and Host Cell Substrate Recognition by Hepatitis C Virus NS3/4A Protease

    SciTech Connect

    Romano, Keith P.; Laine, Jennifer M.; Deveau, Laura M.; Cao, Hong; Massi, Francesca; Schiffer, Celia A.

    2011-08-16

    Hepatitis C NS3/4A protease is a prime therapeutic target that is responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A, and 5A5B and two host cell adaptor proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host cell cleavage sites were determined and compared to the crystal structures of viral substrates. Two distinct protease conformations were observed and correlated with substrate specificity: (i) 3-4A, 4A4B, 5A5B, and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease, and (ii) TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance.

  13. Molecular Mechanisms of Viral and Host Cell Substrate Recognition by Hepatitis C Virus NS3/4A Protease▿

    PubMed Central

    Romano, Keith P.; Laine, Jennifer M.; Deveau, Laura M.; Cao, Hong; Massi, Francesca; Schiffer, Celia A.

    2011-01-01

    Hepatitis C NS3/4A protease is a prime therapeutic target that is responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A, and 5A5B and two host cell adaptor proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host cell cleavage sites were determined and compared to the crystal structures of viral substrates. Two distinct protease conformations were observed and correlated with substrate specificity: (i) 3-4A, 4A4B, 5A5B, and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease, and (ii) TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance. PMID:21507982

  14. Nonpeptidic delta (delta) opioid agonists and antagonists of the diarylmethylpiperazine class: what have we learned?

    PubMed

    Calderon, Silvia N

    2011-01-01

    The discovery of the selective delta (delta) opioid agonists SNC 80 and BW373U86, which possess a diarylmethylpiperazine structure unique among opioids, represented a major advance in the field of delta-opioid ligands. Extensive research has recently been performed to uncover the structure-activity relationships (SAR) of this class of ligands, thereby providing valuable tools for the pharmacological characterization of the delta opioid receptor. This review focuses on the SAR of this unique series of ligands, and provides an overview of the various chemical routes that have been developed and optimized through the years to allow the syntheses of these ligands on a multigram scale. The search for selective delta opioid agonists and antagonists, as well as for those with mixed opioid agonist properties with potential therapeutic value, continues. Several questions regarding the interaction at the molecular level of diphenylmethylpiperazine derivatives and related analogs with opioid receptors and in particular with the delta opioid system still remain unanswered. Indeed, the development and pharmacological characterization of novel nonpeptidic delta opioid ligands remains an active area of research, as it may provide a better understanding of the role of this receptor in multiple disease states and disorders.

  15. Hepatitis Vaccines

    PubMed Central

    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

  16. Nile River Delta, Egypt

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The Nile River Delta of Egypt (30.0N, 31.0E) irrigated by the Nile River and its many distributaries, is some of the richest farm land in the world and home to some 45 million people, over half of Egypt's population. The capital city of Cairo is at the apex of the delta. Just across the river from Cairo can be seen the ancient three big pyramids and sphinx at Giza and the Suez Canal is just to the right of the delta.

  17. Delta Scuti stars: Theory

    NASA Technical Reports Server (NTRS)

    Guzik, J. A.

    1998-01-01

    The purpose of asteroseismology is not only to derive the internal structure of individual stars from their observed oscillation frequencies, but also to test and extend one's understanding of the physics of matter under the extremes of temperature, density, and pressure found in stellar interiors. In this review, the author hopes to point out what one can learn about the Sun by studying (delta) Scuti stars, as well as what one can learn about stars more massive or evolved than the Sun. He discusses some of the difficulties in theoretical approaches to asteroseismology for (delta) Scuti stars, using FG Vir, (delta) Scuti, and CD-24(degree) 7599 as examples.

  18. Disease surveillance of Atlantic herring: molecular characterization of hepatic coccidiosis and a morphological report of a novel intestinal coccidian.

    PubMed

    Friend, Sarah E; Lovy, Jan; Hershberger, Paul K

    2016-07-07

    Surveillance for pathogens of Atlantic herring, including viral hemorrhagic septicemia virus (VHSV), Ichthyophonus hoferi, and hepatic and intestinal coccidians, was conducted from 2012 to 2016 in the NW Atlantic Ocean, New Jersey, USA. Neither VHSV nor I. hoferi was detected in any sample. Goussia clupearum was found in the livers of 40 to 78% of adult herring in varying parasite loads; however, associated pathological changes were negligible. Phylogenetic analysis based on small subunit 18S rRNA gene sequences placed G. clupearum most closely with other extraintestinal liver coccidia from the genus Calyptospora, though the G. clupearum isolates had a unique nucleotide insertion between 604 and 729 bp that did not occur in any other coccidian species. G. clupearum oocysts from Atlantic and Pacific herring were morphologically similar, though differences occurred in oocyst dimensions. Comparison of G. clupearum genetic sequences from Atlantic and Pacific herring revealed 4 nucleotide substitutions and 2 gaps in a 1749 bp region, indicating some divergence in the geographically separate populations. Pacific G. clupearum oocysts were not directly infective, suggesting that a heteroxenous life cycle is likely. Intestinal coccidiosis was described for the first time from juvenile and adult Atlantic herring. A novel intestinal coccidian species was detected based on morphological characteristics of exogenously sporulated oocysts. A unique feature in these oocysts was the presence of 3 long (15.1 ± 5.1 µm, mean ±SD) spiny projections on both ends of the oocyst. The novel morphology of this coccidian led us to tentatively name this parasite G. echinata n. sp.

  19. Disease surveillance of Atlantic herring: molecular characterization of hepatic coccidiosis and a morphological report of a novel intestinal coccidian

    USGS Publications Warehouse

    Friend, Sarah E; Lovey, J; Hershberger, Paul

    2016-01-01

    Surveillance for pathogens of Atlantic herring, including viral hemorrhagic septicemia virus (VHSV),Ichthyophonus hoferi, and hepatic and intestinal coccidians, was conducted from 2012 to 2016 in the NW Atlantic Ocean, New Jersey, USA. Neither VHSV nor I. hoferi was detected in any sample. Goussia clupearum was found in the livers of 40 to 78% of adult herring in varying parasite loads; however, associated pathological changes were negligible. Phylogenetic analysis based on small subunit 18S rRNA gene sequences placed G. clupearum most closely with other extraintestinal liver coccidia from the genus Calyptospora, though the G. clupearum isolates had a unique nucleotide insertion between 604 and 729 bp that did not occur in any other coccidian species. G. clupearum oocysts from Atlantic and Pacific herring were morphologically similar, though differences occurred in oocyst dimensions. Comparison of G. clupearum genetic sequences from Atlantic and Pacific herring revealed 4 nucleotide substitutions and 2 gaps in a 1749 bp region, indicating some divergence in the geographically separate populations. Pacific G. clupearum oocysts were not directly infective, suggesting that a heteroxenous life cycle is likely. Intestinal coccidiosis was described for the first time from juvenile and adult Atlantic herring. A novel intestinal coccidian species was detected based on morphological characteristics of exogenously sporulated oocysts. A unique feature in these oocysts was the presence of 3 long (15.1 ± 5.1 µm, mean ±SD) spiny projections on both ends of the oocyst. The novel morphology of this coccidian led us to tentatively name this parasite G. echinata n. sp.

  20. A molecular epidemiological study of the hepatitis B virus in Thailand after 22 years of universal immunization.

    PubMed

    Yimnoi, Parichat; Posuwan, Nawarat; Wanlapakorn, Nasamon; Tangkijvanich, Pisit; Theamboonlers, Apiradee; Vongpunsawad, Sompong; Poovorawan, Yong

    2016-04-01

    Hepatitis B virus (HBV) infection affects an estimated two billion people worldwide. Since 1992, Thailand implemented universal HBV vaccination as part of the expanded program on immunization (EPI) for newborns. This study aims to compare genotypes and characterize HBV by assessing pre-S/S and basic core promoter (BCP)/precore (PC) mutations in populations born before and after EPI implementation. A nationwide serosurvey conducted in 2014 assessed the impact of universal HBV vaccination in Thailand. Two cohort groups were established based on whether they were born before or after 1992. HBV DNA was amplified from HBsAg positive samples by PCR and sequenced. HBV genotypes, pre-S/S regions, and BCP/PC mutations were characterized. From a total of 5,964 subjects, there were 2,805 (47.0%) and 3,159 (53.0%) individuals who were born before and after EPI implementation, respectively. The overall prevalence of HBsAg was 2.2%. The prevalence of HBsAg was significantly higher in the before EPI group (4.3%) than in the after EPI group (0.3%) (P < 0.001). HBV DNA was detected in 119 samples; 111 HBV-positive samples (93%) were genotype C (subgenotype C1). The "a" determinant mutation was only detected in the "before EPI" group. Twenty-two years after implementation of the EPI program, the HBV carrier rate is significantly reduced. The most prevalent genotype for the remaining HBV was C1. The "vaccine escape" mutant, especially the "a" determinant, was not detected after the launch of the EPI program, and the current HBV vaccine remains highly effective.

  1. Molecular characterization of the Hepatitis B virus genotypes in Colombia: a Bayesian inference on the genotype F.

    PubMed

    Alvarado Mora, Mónica Viviana; Romano, Camila Malta; Gomes-Gouvêa, Michele Soares; Gutierrez, Maria Fernanda; Botelho, Livia; Carrilho, Flair José; Pinho, João Renato Rebello

    2011-01-01

    Hepatitis B is a worldwide health problem affecting about 2 billion people and more than 350 million are chronic carriers of the virus. Nine HBV genotypes (A to I) have been described. The geographical distribution of HBV genotypes is not completely understood due to the limited number of samples from some parts of the world. One such example is Colombia, in which few studies have described the HBV genotypes. In this study, we characterized HBV genotypes in 143 HBsAg-positive volunteer blood donors from Colombia. A fragment of 1306 bp partially comprising HBsAg and the DNA polymerase coding regions (S/POL) was amplified and sequenced. Bayesian phylogenetic analyses were conducted using the Markov Chain Monte Carlo (MCMC) approach to obtain the maximum clade credibility (MCC) tree using BEAST v.1.5.3. Of all samples, 68 were positive and 52 were successfully sequenced. Genotype F was the most prevalent in this population (77%) - subgenotypes F3 (75%) and F1b (2%). Genotype G (7.7%) and subgenotype A2 (15.3%) were also found. Genotype G sequence analysis suggests distinct introductions of this genotype in the country. Furthermore, we estimated the time of the most recent common ancestor (TMRCA) for each HBV/F subgenotype and also for Colombian F3 sequences using two different datasets: (i) 77 sequences comprising 1306 bp of S/POL region and (ii) 283 sequences comprising 681 bp of S/POL region. We also used two other previously estimated evolutionary rates: (i) 2.60 × 10(-4)s/s/y and (ii) 1.5 × 10(-5)s/s/y. Here we report the HBV genotypes circulating in Colombia and estimated the TMRCA for the four different subgenotypes of genotype F.

  2. Characteristics of hepatitis viruses among Egyptian children with acute hepatitis.

    PubMed

    Youssef, Ahmed; Yano, Yoshihiko; El-Sayed Zaki, Maysaa; Utsumi, Takako; Hayashi, Yoshitake

    2013-04-01

    Hepatitis viral infection is hyperendemic in Egypt, western Asia and Africa. However, little is known about the status of hepatitis viruses among rural Egyptian children. Therefore, this study sought to examine the prevalence and characteristics of hepatitis viruses among symptomatic Egyptian children. Serological and molecular analyses of hepatitis viral infection were conducted in 33 children hospitalised at Mansoura University with symptomatic hepatic dysfunction (mean ± standard deviation age, 9.7±3.4 years; alanine aminotransferase level, 130±68 IU/ml). Eleven children (33%) were positive for anti-haemagglutination-IgM and were diagnosed with acute hepatitis A. Hepatitis B surface antigen (HBsAg) and anti‑hepatitis C virus (HCV) were detected in 9 (27%) and 7 (21%) children, respectively, indicating acute-on-chronic infection with hepatitis viruses. None of the children was positive for anti‑hepatitis B core antigen-IgM. Phylogenetic analysis confirmed that all HBVs belonged to genotype D (subgenotype D1) and that HCV belonged to genotypes 4a and 1g. HBV-DNA was detected in 9 children (27%) in the pre-S/S region and in 16 children (48%) in the core promoter/precore region. The Y134F amino acid mutation in the 'α' determinant region was detected in all of the patients. The A1762T/G1764A double mutation, and the T1846A and G1896A single mutations were common in children with occult HBV infection. In conclusion, hepatitis viral infection, including acute-on-chronic infection with HCV and HBV, is common in Egyptian children hospitalised with acute hepatitis.

  3. Stability, orientation and position preference of the stem region (residues 689-703) in Hepatitis C Virus (HCV) envelope glycoprotein E2: a molecular dynamics study

    PubMed Central

    Jusoh, Siti Azma

    2013-01-01

    Envelope glycoproteins of Hepatitis C Virus (HCV) play an important role in the virus assembly and initial entry into host cells. Conserved charged residues of the E2 transmembrane (TM) domain were shown to be responsible for the heterodimerization with envelope glycoprotein E1. Despite intensive research on both envelope glycoproteins, the structural information is still not fully understood. Recent findings have revealed that the stem (ST) region of E2 also functions in the initial stage of the viral life cycle. We have previously shown the effect of the conserved charged residues on the TM helix monomer of E2. Here, we extended the model of the TM domain by adding the adjacent ST segment. Explicit molecular dynamics simulations were performed for the E2 amphiphilic segment of the ST region connected to the putative TM domain (residues 683-746). Structural conformation and behavior are studied and compared with the nuclear magnetic resonance (NMR)-derived segment of E2 ( 2KQZ.pdb). We observed that the central helix of the ST region (residues 689 - 703) remained stable as a helix in-plane to the lipid bilayer. Furthermore, the TM domain appeared to provide minimal contribution to the structural stability of the amphipathic region. This study also provides insight into the orientation and positional preferences of the ST segment with respect to the membrane lipid-water interface. PMID:24555044

  4. Low molecular weight heparin for the prevention of hepatic veno-occlusive disease (VOD) after hematopoietic stem cell transplantation: a prospective phase II study.

    PubMed

    Forrest, D L; Thompson, K; Dorcas, V G; Couban, S H; Pierce, R

    2003-06-01

    We evaluated 40 patients undergoing high-dose chemo/radiotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) (allogeneic (22), autologous (18)) to determine the safety and feasibility of administering low molecular weight heparin (LMWH) as hepatic veno-occlusive disease (VOD) prophylaxis. Patients received a once daily subcutaneous injection of dalteparin 2500 anti-Xa i.u. commencing the day prior to starting HDCT, and continuing until day +30 post HSCT or hospital discharge, whichever came first. Dosage adjustments were made for patients developing renal failure. All bleeding episodes were recorded and graded and VOD was diagnosed and graded according to Seattle criteria. At 100 days of follow-up, the overall survival and probability of regimen-related mortality were 85 and 15%, respectively. Nine patients developed VOD. The probability of developing VOD post allogeneic and autologous HSCT was 28% (95% CI, 6-45) and 17% (95% CI, 0-32), respectively. VOD was graded as moderate (n=8) and severe (n=1). VOD resolved in all cases except for one patient who died secondary to severe VOD and multiorgan failure. Clinically significant bleeding episodes occurred in three patients; 24 patients developed minor bleeding not requiring specific therapy. All bleeding episodes resolved. These results suggest that LMWH for VOD prophylaxis is safe with a low incidence of serious bleeding events. Whether it is superior to unfractionated heparin, however, is unknown and should be addressed within the context of a randomized controlled trial.

  5. Molecular and structural changes related to Hepatitis E virus (HEV) antigen and its expression in testis inducing apoptosis in Mongolian gerbil model.

    PubMed

    Soomro, Majid Hussain; Shi, Ruihan; She, Ruiping; Yang, Yifei; Wang, Tongtong; Wu, Qiaoxing; Li, Heng; Hao, Wenzhuo

    2017-02-09

    Hepatitis E virus (HEV) infection has been associated with a wide range of extrahepatic manifestations, so this study was designed to examine the effect and role of HEV on structural and molecular changes in the testicular tissues of Mongolian gerbils experimentally infected with swine HEV. HEV RNA was first detected in testis at 14 day post inoculation and reached a peak between 28 to 42 days later with viral load between 3.12 logs g-¹ to 6.23 logs g-¹ by PCR assays. Microscopic changes showed vacuolation, sloughing of germ cells, formation of multinuclear giant cells, degeneration, necrosis of tubules and damaged blood-testis barrier was observed through transmission electron microscopy. HEV ORF2 antigen was detected in the sperm cell cytoplasm along with decrease in relative protein of zonula occludens-1 through immunohistochemistry. HEV ORF3 antigen and ZO-1 protein was detectable through western blot. Lower (P<0.05) serum testosterone and higher (P<0.05) blood urea nitrogen (BUN) level was observed in inoculated Mongolian gerbils. Likewise, increased (P<0.05) germ cell apoptosis rate was detected with significant increased expression of Fas-L, Fas in HEV inoculated groups at each time points. Up-regulation (P < 0.05 or P < 0.01) in mRNA level of Fas-L, Fas, Bax, Bcl-2 and caspase-3 were seen in HEV RNA positive testes. Our study demonstrated that after experimental inoculation, HEV can be detected in testis tissues and viral proteins produce structural and molecular changes that in turn disrupt the blood-testis barrier and induce germ cell apoptosis. This article is protected by copyright. All rights reserved.

  6. Recombinative events of the T cell antigen receptor delta gene in peripheral T cell lymphomas.

    PubMed Central

    Kanavaros, P; Farcet, J P; Gaulard, P; Haioun, C; Divine, M; Le Couedic, J P; Lefranc, M P; Reyes, F

    1991-01-01

    Recombinative events of the T cell antigen receptor (TCR) delta-chain gene were studied in 37 cases of peripheral T cell lymphoma (PTCL) and related to their clinical presentation and the expression of the alpha beta or gamma delta heterodimers as determined by immunostaining of frozen tissue samples. There were 22 cases of alpha beta, 5 cases of gamma delta, and 10 cases of silent TCR expressing neither the alpha beta nor gamma delta TCR. 5 different probes were used to examine the delta locus. The 22 cases of alpha beta PTCL displayed biallelic and monoallelic deletions; a monoallelic V delta 1 J delta 1 rearrangement was observed in 1 case and a monoallelic germ line configuration in 7 cases. The 5 cases of gamma delta PTCL displayed biallelic rearrangements: the productive rearrangements could be ascribed to V delta 1J delta 1 joining in 3 cases and VJ delta 1 joining in 2 cases according to the combined pattern of DNA hybridization with the appropriate probes and of cell reactivity with the TCR delta-1, delta TCS-1, and anti-V delta 2 monoclonal antibodies. In the VJ delta 1 joining, the rearranged V segments were located between V delta 1 and V delta 2. Interestingly, in the third group of 10 cases of silent PTCL, 5 cases were found to have a TCR gene configuration identical to that in the TCR alpha beta PTCL, as demonstrated by biallelic delta gene deletion. These 5 cases were CD3 positive. The 5 remaining cases showed a monoallelic delta gene rearrangement with a monoallelic germ line configuration in 4 and a monoallelic deletion in 1. Four of these cases were CD3 negative, which was consistent with an immature genotype the TCR commitent of which could not be ascertained. Finally, TCR gamma delta PTCL consisted of a distinct clinical morphological and molecular entity whereas TCR alpha beta and silent PTCL had a similar presentation. Images PMID:1991851

  7. Feature Hepatitis: Hepatitis Can Strike Anyone

    MedlinePlus

    ... 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 ...

  8. Hepatitis A through E (Viral Hepatitis)

    MedlinePlus

    ... travelers How can hepatitis B be prevented? The hepatitis B vaccine offers the best protection. All infants and unvaccinated ... should receive hepatitis B immune globulin and the hepatitis B vaccine within 12 hours of birth to help prevent ...

  9. Cellular and molecular mechanisms regulating the hepatic erythropoietin expression during acute-phase response: a role for IL-6.

    PubMed

    Ramadori, Pierluigi; Ahmad, Ghayyor; Ramadori, Giuliano

    2010-09-01

    The source of circulating erythropoietin (EPO), the mediators and the mechanisms involved in the upregulation of EPO gene expression during acute-phase reaction are still poorly understood. Acute-phase reaction was induced by either intramuscular turpentine oil (TO) or intraperitoneal lipopolysaccharide (LPS) administration into wild-type and interleukin (IL)-6 knockout (KO) mice. Animals were killed at different time points and blood, liver and muscle tissue were collected. Serum levels of EPO were measured by enzyme-linked immunoadsorbent assay; liver and injured muscle samples were processed for RNA isolation and for protein analysis. EPO, hypoxia-inducible factors 1alpha and 2alpha (HIF-1alpha and HIF-2alpha) mRNA were analyzed by RT-PCR and the protein levels were analyzed by western blot and electrophoretic mobility shift assay. HIF-1alpha and HIF-2alpha localization was performed through immunofluorescence staining. EPO, HIF-1 and HIF-2 gene and protein expression levels were also analyzed in isolated mouse hepatocytes after stimulation with IL-6. In the wild-type animals, EPO serum levels increased dramatically at 12 h after the insults together with the hepatic gene expression. In TO-treated animals, the EPO gene expression reached an 8.2-fold increase at 12 h, and in LPS-treated mice a similar induction was recorded at 6 h (about 4.5-fold increase). In the IL-6KO strain, the upregulation after the inflammatory stimuli was much lower (only 2.0-fold increase). A progressive upregulation of HIF-1alpha and HIF-2alpha was detectable until 6 h after the insults, but only HIF-1alpha upregulation was reduced in IL-6KO mice. In isolated hepatocytes, stimulation with a single dose of IL-6 induced a nuclear accumulation of HIF-1alpha, in parallel with an increase of EPO mRNA. No effect on HIF-2alpha expression was found. IL-6 appears to be the main regulator of EPO gene expression and a major contributor for HIF-1alpha induction in hepatocytes and Kupffer cells

  10. Federal Funding in the Delta.

    ERIC Educational Resources Information Center

    Reeder, Richard J.; Calhoun, Samuel D.

    2002-01-01

    The Lower Mississippi Delta region, especially the rural Delta, faces many economic challenges. The rural Delta has received much federal aid in basic income support and funding for human resource development, but less for community resource programs, which are important for economic development. Federal aid to the Delta is analyzed in terms of…

  11. Hepatitis C Test

    MedlinePlus

    ... Hepatitis C Antibody; Anti-HCV; HCV-PCR; HCV-RNA; Hepatitis C Viral Load Formal name: Viral Hepatitis C Antibody Screen; Viral Hepatitis C RNA by PCR; Hepatitis C Virus Genotype Related tests: ...

  12. Alcohol and Hepatitis

    MedlinePlus

    ... Home » Living with Hepatitis » Daily Living: Alcohol Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Alcohol for Veterans and the Public Alcohol and Hepatitis: Entire Lesson Overview Alcohol is one of the ...

  13. Hepatitis C: Clinical Trials

    MedlinePlus

    ... 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 ...

  14. Hepatitis (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Hepatitis KidsHealth > For Parents > Hepatitis Print A A A ... to Call the Doctor en español Hepatitis About Hepatitis The word hepatitis simply means an inflammation of ...

  15. Travelers' Health: Hepatitis B

    MedlinePlus

    ... Chapter 3 - Hepatitis A Chapter 3 - Hepatitis C Hepatitis B Francisco Averhoff INFECTIOUS AGENT Hepatitis B is ... their exposures. Map 3-04. Prevalence of chronic hepatitis B virus infection among adults PDF Version (printable) ...

  16. Adipocytokines and Hepatic Fibrosis

    PubMed Central

    Saxena, Neeraj K.; Anania, Frank A.

    2015-01-01

    Obesity and metabolic syndrome pose significant risk for progression of many types of chronic illnesses, including liver disease. Hormones released from adipocytes, adipocytokines, associated with obesity and metabolic syndrome, have been shown to control hepatic inflammation and fibrosis. Hepatic fibrosis is the final common pathway that can result in cirrhosis, and can ultimately require liver transplantation. Initially, two key adipocytokines, leptin and adiponectin, appeared to control many fundamental aspects of the cell and molecular biology related to hepatic fibrosis and its resolution. Leptin appears to act as a profibrogenic molecule while adiponectin possesses strong-anti-fibrotic properties. In this review, we emphasize pertinent data associated with these, and recently discovered, adipocytokines that may drive or halt the fibrogenic response in the liver. PMID:25656826

  17. Hepatitis A

    MedlinePlus

    ... inflammation of the liver.” This inflammation can be caused by a wide variety of toxins, drugs, and metabolic diseases, as well as infection. There are at least 5 hepatitis viruses. Hepatitis A is contracted when a child eats food or drinks water that is contaminated with the virus or has ...

  18. Hepatitis B

    MedlinePlus

    ... B to come back?Should I get the hepatitis B vaccine?What are the side effects of antiviral medicines?Will my liver ever be normal again? Last Updated: October 1996 This article ... B, hepatitis virus, Interferon alpha-2b, jaundice, Lamivudine, liver ...

  19. Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus Transmitted/Founder Variants by RIG-I Is Dependent on U-Core Length

    PubMed Central

    Kell, Alison; Stoddard, Mark; Li, Hui; Marcotrigiano, Joe; Shaw, George M.

    2015-01-01

    ABSTRACT Despite the introduction of direct-acting antiviral (DAA) drugs against hepatitis C virus (HCV), infection remains a major public health concern because DAA therapeutics do not prevent reinfection and patients can still progress to chronic liver disease. Chronic HCV infection is supported by a variety of viral immune evasion strategies, but, remarkably, 20% to 30% of acute infections spontaneously clear prior to development of adaptive immune responses, thus implicating innate immunity in resolving acute HCV infection. However, the virus-host interactions regulating acute infection are unknown. Transmission of HCV involves one or a few transmitted/founder (T/F) variants. In infected hepatocytes, the retinoic acid-inducible gene I (RIG-I) protein recognizes 5′ triphosphate (5′ppp) of the HCV RNA and a pathogen-associated molecular pattern (PAMP) motif located within the 3′ untranslated region consisting of poly-U/UC. PAMP binding activates RIG-I to induce innate immune signaling and type 1 interferon antiviral defenses. HCV poly-U/UC sequences can differ in length and complexity, suggesting that PAMP diversity in T/F genomes could regulate innate immune control of acute HCV infection. Using 14 unique poly-U/UC sequences from HCV T/F genomes recovered from acute-infection patients, we tested whether RIG-I recognition and innate immune activation correlate with PAMP sequence characteristics. We show that T/F variants are recognized by RIG-I in a manner dependent on length of the U-core motif of the poly-U/UC PAMP and are recognized by RIG-I to induce innate immune responses that restrict acute infection. PAMP recognition of T/F HCV variants by RIG-I may therefore impart innate immune signaling and HCV restriction to impact acute-phase-to-chronic-phase transition. IMPORTANCE Recognition of nonself molecular patterns such as those seen with viral nucleic acids is an essential step in triggering the immune response to virus infection. Innate immunity is

  20. Molecular magnetic resonance imaging of activated hepatic stellate cells with ultrasmall superparamagnetic iron oxide targeting integrin αvβ3 for staging liver fibrosis in rat model

    PubMed Central

    Zhang, Caiyuan; Liu, Huanhuan; Cui, Yanfen; Li, Xiaoming; Zhang, Zhongyang; Zhang, Yong; Wang, Dengbin

    2016-01-01

    Purpose To evaluate the expression level of integrin αvβ3 on activated hepatic stellate cells (HSCs) at different stages of liver fibrosis induced by carbon tetrachloride (CCl4) in rat model and the feasibility to stage liver fibrosis by using molecular magnetic resonance imaging (MRI) with arginine-glycine-aspartic acid (RGD) peptide modified ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) specifically targeting integrin αvβ3. Materials and methods All experiments received approval from our Institutional Animal Care and Use Committee. Thirty-six rats were randomly divided into three groups of 12 subjects each, and intraperitoneally injected with CCl4 for either 3, 6, or 9 weeks. Controls (n=10) received pure olive oil. The change in T2* relaxation rate (ΔR2*) pre- and postintravenous administration of RGD-USPIO or naked USPIO was measured by 3.0T clinical MRI and compared by one-way analysis of variance or the Student’s t-test. The relationship between expression level of integrin αvβ3 and liver fibrotic degree was evaluated by Spearman’s ranked correlation. Results Activated HSCs were confirmed to be the main cell types expressing integrin αvβ3 during liver fibrogenesis. The protein level of integrin αv and β3 subunit expressed on activated HSCs was upregulated and correlated well with the progression of liver fibrosis (r=0.954, P<0.001; r=0.931, P<0.001, respectively). After injection of RGD-USPIO, there is significant difference in ΔR2* among rats treated with 0, 3, 6, and 9 weeks of CCl4 (P<0.001). The accumulation of iron particles in fibrotic liver specimen is significantly greater for RGD-USPIO than naked USPIO after being injected with equal dose of iron. Conclusion Molecular MRI of integrin αvβ3 expressed on activated HSCs by using RGD-USPIO may distinguish different liver fibrotic stages in CCl4 rat model and shows promising to noninvasively monitor the progression of the liver fibrosis and therapeutic response to

  1. Delta II Mars Pathfinder

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Final preparations for lift off of the DELTA II Mars Pathfinder Rocket are shown. Activities include loading the liquid oxygen, completing the construction of the Rover, and placing the Rover into the Lander. After the countdown, important visual events include the launch of the Delta Rocket, burnout and separation of the three Solid Rocket Boosters, and the main engine cutoff. The cutoff of the main engine marks the beginning of the second stage engine. After the completion of the second stage, the third stage engine ignites and then cuts off. Once the third stage engine cuts off spacecraft separation occurs.

  2. Prevalence of hepatitis A virus infection in Goiânia, Goiás, Brazil, by molecular and serological procedures, 1995-2002.

    PubMed

    Fiaccadori, Fabíola Souza; Soares, Célia Maria de Almeida; Borges, Ana Maria Tavares; Cardoso, Divina das Dôres de Paula

    2006-06-01

    In this study, a total of 865 serum samples were collected between 1995 and 2002 from individuals living in Goiânia, Central Brazil, and clinically suspected of hepatitis. After exclusion of 162 samples which were positive for hepatitis B virus or hepatitis C virus, 703 samples were tested for anti-hepatitis A virus (anti-HAV) IgM antibodies by enzyme immunoassay. In addition, 588 of these samples and 22 fecal samples were analyzed by reverse transcription-nested PCR for HAV RNA detection, with positivity indices of 13.1% (77/588) and 54.5% (12/22), respectively. A similar index of viral RNA detection in anti-HAV-IgM positive or negative samples was observed in serum samples. HAV infection is a public health problem worldwide and this study underscores the extent of HAV circulation in our region.

  3. Serum immunoglobulin M antibody to hepatitis D as a surrogate marker of hepatitis D in interferon-treated patients and in patients who underwent liver transplantation.

    PubMed

    Borghesio, E; Rosina, F; Smedile, A; Lagget, M; Niro, M G; Marinucci, G; Rizzetto, M

    1998-03-01

    The kinetics of the immunoglobulin (Ig) M type antibody to the hepatitis D virus (IgM anti-HD) were investigated in hepatitis B surface antigen (HBsAg) carriers with chronic hepatitis D treated with interferon (IFN) and in patients with terminal hepatitis delta virus (HDV) cirrhosis who underwent liver transplantation. The IgM antibody disappeared in each of 8 patients who responded to IFN therapy with the persistent normalization of aminotransferases and with the clearance of serum HBsAg and HDV-RNA. The IgM reactivity did not decline in the 45 treated patients who did not respond to the cytokine or who experienced a relapse after responding while on therapy. The antibody rapidly disappeared from serum post-transplantation in each of 10 examined patients with HDV who underwent transplantation. In 5 patients who underwent transplantation and who became reinfected with HDV, the antibody remained undetectable during the early reinfection phase, as marked by HDV replication and by the absence of liver damage; however, it rapidly raised to pre-transplantation levels with the recurrence of hepatitis D (HD) in the liver graft. Monomeric 7S IgM anti-HD predominated over pentameric 19S antibody in each of the two patients examined for IgM anti-HD molecular species. The IgM antibody to HDV raises in response to HDV-induced damage and represents a valid surrogate marker of liver damage which is immunopathologically related to HDV infection. Besides providing diagnostic information, it provides the best predictor of impending resolution of chronic HDV disease, whether spontaneous or IFN-induced.

  4. DELTA PHASE PLUTONIUM ALLOYS

    DOEpatents

    Cramer, E.M.; Ellinger, F.H.; Land. C.C.

    1960-03-22

    Delta-phase plutonium alloys were developed suitable for use as reactor fuels. The alloys consist of from 1 to 4 at.% zinc and the balance plutonium. The alloys have good neutronic, corrosion, and fabrication characteristics snd possess good dimensional characteristics throughout an operating temperature range from 300 to 490 deg C.

  5. Hepatitis A

    MedlinePlus

    ... bowel movements Loss of appetite Low-grade fever Dark urine Joint pain Yellowing of the skin and ... person ingests even tiny amounts of contaminated fecal matter. The hepatitis A virus infects liver cells and ...

  6. Hepatic Encephalopathy

    MedlinePlus Videos and Cool Tools

    ... 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 ...

  7. Hepatitis E

    MedlinePlus

    ... with a positive-sense, single-stranded ribonucleic acid (RNA) genome. The virus has at least 4 different ... RT-PCR) to detect the hepatitis E virus RNA in blood and/or stool; this assay requires ...

  8. Autoimmune hepatitis.

    PubMed

    Heneghan, Michael A; Yeoman, Andrew D; Verma, Sumita; Smith, Alastair D; Longhi, Maria Serena

    2013-10-26

    Autoimmune hepatitis is a disease of the hepatic parenchyma that can present in acute or chronic forms. In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity. This dichotomy has made definition of a unifying hypothesis in the pathophysiology of the disease difficult, although data from the past 8 years have drawn attention to the role of regulatory T cells. Several triggers have been identified, and the disease arises in genetically susceptible individuals. Clinical and biochemical remission is achievable in up to 85% of cases. For the remaining patients, alternative immunosuppression strategies are an option. Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma. Variant or overlapping syndromes are worthy of consideration when unexpected disease features arise.

  9. Hepatitis E.

    PubMed

    Krawczynski, K; Aggarwal, R; Kamili, S

    2000-09-01

    Hepatitis E, previously known as enterically transmitted non-A, non-B hepatitis, is an infectious viral disease with clinical and morphologic features of acute hepatitis. Its causative agent, hepatitis E virus, consists of small, 32- to 34-nm diameter, icosahedral, nonenveloped particles with a single-stranded, positive-sense, 7.5-kb RNA. The virus has two main geographically distinct strains, Asian and Mexican; recently, novel isolates from nonendemic areas and a genetically related swine HEV have been described. HEV is responsible for large epidemics of acute hepatitis and a proportion of sporadic hepatitis cases in the Indian subcontinent, southeast and central Asia, the Middle East, parts of Africa, and Mexico. The virus is excreted in feces and is transmitted predominantly by fecal-oral route, usually through contaminated water. Person-to-person transmission is uncommon. Clinical attack rates are the highest among young adults. Recent evidence suggests that humans with subclinical HEV infection and animals may represent reservoirs of HEV; however, further data are needed. Diagnosis of hepatitis E is usually made by detection of specific IgM antibody, which disappears rapidly over a few months; IgG anti-HEV persists for at least a few years. Clinical illness is similar to other forms of acute viral hepatitis except in pregnant women, in whom illness is particularly severe with a high mortality rate. Subclinical and unapparent infections may occur; however, chronic infection is unknown. No specific treatment is yet available. Use of clean drinking water and proper sanitation is currently the most effective method of prevention. Passive immunization has not been proved to be effective, and recombinant vaccines for travelers to disease-endemic areas and for pregnant women currently are being developed.

  10. The Devil's in the Delta

    ERIC Educational Resources Information Center

    Luyben, William L.

    2007-01-01

    Students frequently confuse and incorrectly apply the several "deltas" that are used in chemical engineering. The deltas come in three different flavors: "out minus in", "big minus little" and "now versus then." The first applies to a change in a stream property as the stream flows through a process. For example, the "[delta]H" in an energy…

  11. Hepatitis A Test

    MedlinePlus

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Hepatitis A Testing Share this page: Was this page ... HAV-Ab total; Anti-HAV Formal name: Viral Hepatitis A Antibody Related tests: Hepatitis B Testing ; Hepatitis ...

  12. Travelers' Health: Hepatitis A

    MedlinePlus

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

  13. Hepatitis B Foundation

    MedlinePlus

    ... 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 ...

  14. Hepatitis A FAQs

    MedlinePlus

    ... Professional Resources Patient Education Resources Quick Links to Hepatitis … A | B | C | D | E Viral Hepatitis Home ... Grantees Policy and Programs Resource Center Viral Hepatitis Hepatitis A Questions and Answers for the Public Recommend ...

  15. Hepatitis (For Parents)

    MedlinePlus

    ... people at risk for contracting hepatitis. But frequent hand washing and good hygiene practices can reduce this risk. ... After Having Hepatitis B? Hepatitis B (HBV) Hepatitis Hand Washing Blood Transfusions Body Piercing Tattoos Contact Us Print ...

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

    MedlinePlus

    ... 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 ...

  17. DELTAS: A new Global Delta Sustainability Initiative (Invited)

    NASA Astrophysics Data System (ADS)

    Foufoula-Georgiou, E.

    2013-12-01

    Deltas are economic and environmental hotspots, food baskets for many nations, home to a large part of the world population, and hosts of exceptional biodiversity and rich ecosystems. Deltas, being at the land-water interface, are international, regional, and local transport hubs, thus providing the basis for intense economic activities. Yet, deltas are deteriorating at an alarming rate as 'victims' of human actions (e.g. water and sediment reduction due to upstream basin development), climatic impacts (e.g. sea level rise and flooding from rivers and intense tropical storms), and local exploration (e.g. sand or aggregates, groundwater and hydrocarbon extraction). Although many efforts exist on individual deltas around the world, a comprehensive global delta sustainability initiative that promotes awareness, science integration, data and knowledge sharing, and development of decision support tools for an effective dialogue between scientists, managers and policy makers is lacking. Recently, the international scientific community proposed to establish the International Year of Deltas (IYD) to serve as the beginning of such a Global Delta Sustainability Initiative. The IYD was proposed as a year to: (1) increase awareness and attention to the value and vulnerability of deltas worldwide; (2) promote and enhance international and regional cooperation at the scientific, policy, and stakeholder level; and (3) serve as a launching pad for a 10-year committed effort to understand deltas as complex socio-ecological systems and ensure preparedness in protecting and restoring them in a rapidly changing environment. In this talk, the vision for such an international coordinated effort on delta sustainability will be presented as developed by a large number of international experts and recently funded through the Belmont Forum International Opportunities Fund. Participating countries include: U.S., France, Germany, U.K., India, Japan, Netherlands, Norway, Brazil, Bangladesh

  18. Understanding pesticides in California's Delta

    USGS Publications Warehouse

    Kuivila, Kathryn; Orlando, James L.

    2012-01-01

    The Sacramento-San Joaquin River Delta (Delta) is the hub of California’s water system and also an important habitat for imperiled fish and wildlife. Aquatic organisms are exposed to mixtures of pesticides that flow through the maze of Delta water channels from sources including agricultural, landscape, and urban pest-control applications. While we do not know all of the effects pesticides have on the ecosystem, there is evidence that they cause some damage to organisms in the Delta. Decades of USGS research have provided a good understanding of when, where, and how pesticides enter the Delta. However, pesticide use is continually changing. New field studies and methods are needed so that scientists can analyze which pesticides are present in the Delta, and at what concentrations, enabling them to estimate exposure and ultimate effects on organisms. Continuing research will provide resource managers and stakeholders with crucial information to manage the Delta wisely.

  19. Martian deltas: Morphology and distribution

    NASA Technical Reports Server (NTRS)

    Rice, J. W., Jr.; Scott, D. H.

    1993-01-01

    Recent detailed mapping has revealed numerous examples of Martian deltas. The location and morphology of these deltas are described. Factors that contribute to delta morphology are river regime, coastal processes, structural stability, and climate. The largest delta systems on Mars are located near the mouths of Maja, Maumee, Vedra, Ma'adim, Kasei, and Brazos Valles. There are also several smaller-scale deltas emplaced near channel mouths situated in Ismenius Lacus, Memnonia, and Arabia. Delta morphology was used to reconstruct type, quantity, and sediment load size transported by the debouching channel systems. Methods initially developed for terrestrial systems were used to gain information on the relationships between Martian delta morphology, river regime, and coastal processes.

  20. Hepatitis C: Sex and Sexuality

    MedlinePlus

    ... 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 ...

  1. Natural processes in delta restoration: application to the Mississippi Delta.

    PubMed

    Paola, Chris; Twilley, Robert R; Edmonds, Douglas A; Kim, Wonsuck; Mohrig, David; Parker, Gary; Viparelli, Enrica; Voller, Vaughan R

    2011-01-01

    Restoration of river deltas involves diverting sediment and water from major channels into adjoining drowned areas, where the sediment can build new land and provide a platform for regenerating wetland ecosystems. Except for local engineered structures at the points of diversion, restoration mainly relies on natural delta-building processes. Present understanding of such processes is sufficient to provide a basis for determining the feasibility of restoration projects through quantitative estimates of land-building rates and sustainable wetland area under different scenarios of sediment supply, subsidence, and sea-level rise. We are not yet to the point of being able to predict the evolution of a restored delta in detail. Predictions of delta evolution are based on field studies of active deltas, deltas in mine-tailings ponds, experimental deltas, and countless natural experiments contained in the stratigraphic record. These studies provide input for a variety of mechanistic delta models, ranging from radially averaged formulations to more detailed models that can resolve channels, topography, and ecosystem processes. Especially exciting areas for future research include understanding the mechanisms by which deltaic channel networks self-organize, grow, and distribute sediment and nutrients over the delta surface and coupling these to ecosystem processes, especially the interplay of topography, network geometry, and ecosystem dynamics.

  2. Delta in Eberswalde

    NASA Technical Reports Server (NTRS)

    2006-01-01

    This HiRISE image covers a portion of a delta that partially fills Eberswalde crater in Margaritifer Sinus. The delta was first recognized and mapped using MOC images that revealed various features whose presence required sustained flow and deposition into a lake that once occupied the crater. The HiRISE image resolves meter-scale features that record the migration of channels and delta distributaries as the delta grew over time. Differences in grain-size of sediments within the environments on the delta enable differential erosion of the deposits. As a result, coarser channel deposits are slightly more resistant and stand in relief relative to finer-grained over-bank and more easily eroded distal delta deposits. Close examination of the relict channel deposits confirms the presence of some meter-size blocks that were likely too coarse to have been transported by water flowing within the channels. These blocks may be formed of the sand and gravel that more likely moved along the channels that was lithified and eroded. Numerous meter-scale polygonal structures are common on many surfaces, but mostly those associated with more quiescent depositional environments removed from the channels. The polygons could be the result of deposition of fine-grained sediments that were either exposed and desiccated (dried out), rich in clays that shrunk when the water was removed, turned into rock and then fractured and eroded, or some combination of these processes.

    Image PSP_001336_1560 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on November 8, 2006. The complete image is centered at -23.8 degrees latitude, 326.4 degrees East longitude. The range to the target site was 256.3 km (160.2 miles). At this distance the image scale is 25.6 cm/pixel (with 1 x 1 binning) so objects 77 cm across are resolved. The image shown here has been map-projected to 25 cm/pixel and north is up. The image was

  3. Pioneer Launch on Delta Vehicle

    NASA Technical Reports Server (NTRS)

    1969-01-01

    NASA launches the last in the series of interplanetary Pioneer spacecraft, Pioneer 10 from Cape Kennedy, Florida. The long-tank Delta launch vehicle placed the spacecraft in a solar orbit along the path of Earth's orbit. The spacecraft then passed inside and outside Earth's orbit, alternately speeding up and slowing down relative to Earth. The Delta launch vehicle family started development in 1959. The Delta was composed of parts from the Thor, an intermediate-range ballistic missile, as its first stage, and the Vanguard as its second. The first Delta was launched from Cape Canaveral on May 13, 1960 and was powerful enough to deliver a 100-pound spacecraft into geostationary transfer orbit. Delta has been used to launch civil, commercial, and military satellites into orbit. For more information about Delta, please see Chapter 3 in Roger Launius and Dennis Jenkins' book To Reach the High Frontier published by The University Press of Kentucky in 2002.

  4. [Delta-9-tetrahydrocannabinol pharmacokinetics].

    PubMed

    Goullé, J-P; Saussereau, E; Lacroix, C

    2008-08-01

    Delta-9-tetrahydrocannabinol (Delta-9-THC) is the main psychoactive ingredient of cannabis. Smoking is currently most common use of cannabis. The present review focuses on the pharmacokinetics of THC. The variability of THC in plant material which has significantly increased in recent years leads to variability in tissue THC levels from smoking, which is, in itself, a highly individual process. This variability of THC content has an important impact on drug pharmacokinetics and pharmacology. After smoking THC bioavailability averages 30%. With a 3.55% THC cigarette, a peak plasma level near 160 ng/mL occurs approximately 10 min after inhalation. THC is eliminated quickly from plasma in a multiphasic manner and is widely distributed to tissues, which is responsible for its pharmacologic effects. Body fat then serves as a long-term storage site. This particular pharmacokinetics explains the noncorrelation between THC blood level and clinical effects as is observed for ethanol. A major active 11-hydroxy metabolite is formed after both inhalation and oral dosing (20 and 100% of parent, respectively). The elimination of THC and its many metabolites, mainly THC-COOH, occurs via the feces and urine for several weeks. Thus, to confirm abstinence, urine THC-COOH analysis would be a useful tool. A positive result could be checked by gas chromatography-mass spectrometry THC blood analysis, indicative of a recent cannabis exposure.

  5. Importance of molecular typing in confirmation of the source of a national hepatitis A virus outbreak in Norway and the detection of a related cluster in Germany.

    PubMed

    Guzman-Herrador, Bernardo R; Panning, Marcus; Stene-Johansen, Kathrine; Borgen, Katrine; Einöder-Moreno, Margot; Huzly, Daniela; Jensvoll, Laila; Lange, Heidi; Maassen, Sigrid; Myking, Solveig; Myrmel, Mette; Neumann-Haefelin, Christoph; Nygård, Karin; Wenzel, Jürgen J; Øye, Ann Kristin; Vold, Line

    2015-11-01

    In March 2014, after an increase of notifications of domestically acquired hepatitis A virus infections, an outbreak investigation was launched in Norway. Sequenced-based typing results showed that these cases were associated with a strain that was identical to one causing an ongoing multinational outbreak in Europe linked to frozen mixed berries. Thirty-three confirmed cases with the outbreak strain were notified in Norway from November 2013 to June 2014. Epidemiological evidence and trace-back investigations linked the outbreak to the consumption of a berry mix cake. Identification of the hepatitis A virus outbreak strain in berries from one of the implicated cakes confirmed the cake to be the source. Subsequently, a cluster in Germany linked to the cake was also identified.

  6. Hepatitis B virus infection in multitransfused haemophiliacs.

    PubMed Central

    Nebbia, G; Moroni, G A; Simoni, L; Belli, M; Carnelli, V

    1986-01-01

    A longitudinal study of 44 haemophilic children, all in a treatment programme with factor concentrates, was undertaken to evaluate the occurrence, characteristics, and evolution of hepatitis B virus (HBV) infection. Twenty four children (55%) (group I) showed signs of HBV infection, while 20 (45%) (group II) did not. Age at onset of treatment, number of infusions, and total amount of concentrate received did not show significant differences between the two groups. In group I only four children (16%) had symptomatic acute hepatitis. Chronic liver disease was present in nine patients (38% of infected children). The early age of infection would seem to be an important factor for predicting chronic evolution. Evidence of delta infection in three children with severe liver disease seemed to confirm the high pathogenicity of this agent. Because of the risks associated with chronic HBV infection a careful follow up of patients positive for hepatitis B surface antigen is mandatory. PMID:3089179

  7. Hepatitis B virus (image)

    MedlinePlus

    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 ...

  8. Hepatitis Risk Assessment

    MedlinePlus

    ... please visit this page: About CDC.gov . Hepatitis Risk Assessment Recommend on Facebook Tweet Share Compartir Viral Hepatitis. ... you at risk? Take this 5 minute Hepatitis Risk Assessment developed by the CDC and get a personalized ...

  9. Preventing hepatitis A

    MedlinePlus

    Hepatitis A is inflammation (irritation and swelling) of the liver caused by the hepatitis A virus. You can take several steps to ... reduce your risk of spreading or catching the hepatitis A virus: Always wash your hands thoroughly after ...

  10. Hepatitis B Test

    MedlinePlus

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Hepatitis B Testing Share this page: Was this page ... known as: HBV Tests; Hep B; anti-HBs; Hepatitis B Surface Antibody; HBsAg; Hepatitis B Surface Antigen; ...

  11. HIV and Hepatitis C

    MedlinePlus

    ... AIDS-Related Opportunistic Infections and Coinfections HIV and Hepatitis C (Last updated 8/31/2016; last reviewed ... the medicines for any side effects. What is hepatitis C? Hepatitis C is a liver disease caused ...

  12. HIV and Hepatitis B

    MedlinePlus

    ... AIDS-Related Opportunistic Infections and Coinfections HIV and Hepatitis B (Last updated 8/31/2016; last reviewed ... should be treated for both diseases. What is hepatitis B? Hepatitis B is a liver disease caused ...

  13. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  14. [Novel treatments for hepatitis C viral infection and the hepatic fibrosis].

    PubMed

    Lugo-Baruqui, Alejandro; Bautista López, Carlos Alfredo; Armendáriz-Borunda, Juan

    2009-02-01

    Hepatitis C virus (HCV) infection represents a global health problem due to its evolution to hepatic cirrhosis and hepatocellular carcinoma. The viral pathogenesis and infectious processes are not yet fully understood. The development of natural viral resistance towards the host immune system represents a mayor challenge for the design of alternative therapeutic interventions and development of viral vaccines. The molecular mechanisms of hepatic fibrosis are well described. New alternatives for the treatment of patients with HCV infection and hepatic cirrhosis are under intensive research. New drugs such as viral protease inhibitors and assembly inhibitors, as well as immune modulators have been studied in clinical trials. Additional alternatives include antifibrotic drugs, which reverse the hepatic cellular damage caused by HCV infection. This review makes reference to viral infective mechanisms, molecular pathways of liver fibrosis and overviews conventional and new treatments for HCV infection and liver fibrosis.

  15. Mackenzie River Delta, Canada

    NASA Technical Reports Server (NTRS)

    2007-01-01

    The Mackenzie River in the Northwest Territories, Canada, with its headstreams the Peace and Finley, is the longest river in North America at 4241 km, and drains an area of 1,805,000 square km. The large marshy delta provides habitat for migrating Snow Geese, Tundra Swans, Brant, and other waterfowl. The estuary is a calving area for Beluga whales. The Mackenzie (previously the Disappointment River) was named after Alexander Mackenzie who travelled the river while trying to reach the Pacific in 1789.

    The image was acquired on August 4, 2005, covers an area of 55.8 x 55.8 km, and is located at 68.6 degrees north latitude, 134.7 degrees west longitude.

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  16. Colorado River Delta

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Colorado River ends its 2330 km journey in the Gulf of Mexico in Baja California. The heavy use of the river as an irrigation source for the Imperial Valley has dessicated the lower course of the river in Mexico such that it no longer consistently reaches the sea. Prior to the mid 20th century, the Colorado River Delta provided a rich estuarine marshland that is now essentially desiccated, but nonetheless is an important ecological resource.

    The image was acquired May 29, 2006, covers an area of 44.3 x 57.5 km, and is located at 32.1 degrees north latitude, 115.1 degrees west longitude.

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  17. "Delta Plots"--A New Way to Visualize Electronic Excitation.

    ERIC Educational Resources Information Center

    Morrison, Harry; And Others

    1985-01-01

    Presents procedures for obtaining and examples of delta plots (a way of illustrating electron density changes associated with electronic excitation). These plots are pedagogically useful for visualizing simple and complex transitions and provide a way of "seeing" the origin of highest occupied molecular orbital (HOMO)-dictated carbonyl…

  18. Hepatitis B Vaccine

    MedlinePlus

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

  19. Erosion Between Two Delta Fronts, the Mekong Delta Case

    NASA Astrophysics Data System (ADS)

    Unverricht, D.; Heinrich, C.; Nguyen, T. C.; Szczucinski, W.; Schwarzer, K.; Stattegger, K.

    2013-12-01

    Human activities, like embanking, sand mining, groundwater extraction and deforestation lead to strong changes of the deltaic environment. Especially, mangrove cutting influences strongly the coastal erosion along large areas of the southern Mekong delta coast. However, all currently published data document erosion from subaerial areas excluding the subaqueous Mekong delta. Our study fills this gap along the subaqueous Mekong Delta between the Bassac River mouth and the Gulf of Thailand. Hydroacoustic profiles and sediment coring were carried out during two cruises in 2007 and 2008. Analyses of ADCP measurements provide valuable information of current direction and velocity during the inter-monsoon season. Fine sediment dynamics including SPM were analyzed applying laser in situ scattering and Transmissiometry (LISST) at vertical profiles. Two delta fronts were found more than 200 km apart, one in front of the main Mekong river distributaries and the other around Ca Mau Cape, the south-western most spit of the Mekong River Delta. Although the delta front around Ca Mau Cape is not directly supplied by the main distributaries of the Mekong River, it is the fastest prograding region of the subaqueous Mekong delta. Alongshore sediment transport takes place from the north-eastern main distributaries towards south-west (Ca Mau Cape). Between both delta fronts, a large scale alternating sand-ridge-system, at least 120 km long and 6 to 10 km wide (ridge crest distance), has developed where erosional channels separate two sand-ridge bodies. The origin of the sand-ridge system is situated at the delta slope off Ganh Hao around water depths between 10 and 18 m. Here, the delta slope consists mainly of fine sand in the upper layer (up to 20 cm thickness) and is separated by an erosional hiatus from the lower muddy layer. The mangroves and sandy beaches at the coast in this region are also under erosion. It is assumed that the eroded beach sand feeds the sand-ridge-system. The

  20. Thalamic mechanisms underlying alpha-delta sleep with implications for fibromyalgia

    PubMed Central

    Klerman, Elizabeth B.; Adler, Gail K.; Kopell, Nancy J.

    2015-01-01

    Alpha-delta sleep is the abnormal intrusion of alpha activity (8- to 13-Hz oscillations) into the delta activity (1- to 4-Hz oscillations) that defines slow-wave sleep. Alpha-delta sleep is especially prevalent in fibromyalgia patients, and there is evidence suggesting that the irregularities in the sleep of these patients may cause the muscle and tissue pain that characterizes the disorder. We constructed a biophysically realistic mathematical model of alpha-delta sleep. Imaging studies in fibromyalgia patients suggesting altered levels of activity in the thalamus motivated a thalamic model as the source of alpha activity. Since sodium oxybate helps to alleviate the symptoms of fibromyalgia and reduces the amount of alpha-delta sleep in fibromyalgia patients, we examined how changes in the molecular targets of sodium oxybate affected alpha-delta activity in our circuit. Our model shows how alterations in GABAB currents and two thalamic currents, Ih (a hyperpolarization-activated current) and a potassium leak current, transform a circuit that normally produces delta oscillations into one that produces alpha-delta activity. Our findings suggest that drugs that reduce Ih conductances and/or increase potassium conductances, without necessarily increasing GABAB conductances, might be sufficient to restore delta sleep. Furthermore, they suggest that delta sleep might be restored by drugs that preferentially target these currents in the thalamus; such drugs might have fewer side effects than drugs that act systemically. PMID:26245315

  1. Artificial delta growth

    NASA Astrophysics Data System (ADS)

    Mikeš, Daniel

    2010-05-01

    A deltaic sedimentary system has a point source; sediment is carried over the delta plain by distributary channels away from the point source and deposited at the delta front by distributary mouth bars. The established methods to describe such a sedimentary system are "bedding analysis", "facies analysis", and "basin analysis". We shall call the ambient conditions "input" and the rock record "output". There exist a number of methods to deduce input from output, e.g. "Sequence stratigraphy" (a.o. Vail et al. 1977, Catuneanu et al. 2009), "Shoreline trajectory" (a.o. Helland-Hansen & Martinsen 1996, Helland-Hansen & Hampson 2009) on the one hand and the complex use of established techniques on the other (a.o. Miall & Miall 2001, Miall & Miall 2002). None of these deductive methods seems to be sufficient. I claim that the common errors in all these attempts are the following: (1) a sedimentary system is four-dimensional (3+1) and a lesser dimensional analysis is insufficient; (2) a sedimentary system is complex and any empirical/deductive analysis is non-unique. The proper approach to the problem is therefore the theoretical/inductive analysis. To that end we performed six scenarios of a scaled version of a passive margin delta in a flume tank. The scenarios have identical stepwise tectonic subsidence and semi-cyclic sealevel, but different supply curves, i.e. supply is: constant, highly-frequent, proportional to sealevel, inversely proportional to sealevel, lagging to sealevel, ahead of sealevel. The preliminary results are indicative. Lobe-switching occurs frequently and hence locally sedimentation occurs shortly and hiatuses are substantial; therefore events in 2D (+1) cross-sections don't correlate temporally. The number of sedimentary cycles disequals the number of sealevel cycles. Lobe-switching and stepwise tectonic subsidence cause onlap/transgression. Erosional unconformities are local diachronous events, whereas maximum flooding surfaces are regional

  2. Delta beta-thalassaemia in southern Italy: evidence for a single mutational event.

    PubMed Central

    Carè, A; Sposi, N M; Giampaolo, A; Improta, T; Calandrini, M; Petrini, M; Marinucci, M; Tagarelli, A; Brancati, C

    1984-01-01

    Haematological and molecular studies on 32 heterozygotes for G gamma A gamma delta beta(0)-thalassaemia from 15 unrelated families from southern Italy are reported. The haematological features of G gamma A gamma delta beta(0)-thalassaemia carriers are compared with those of beta-thalassaemia and Hb Lepore heterozygotes. Striking similarity exists between the phenotypic expression of beta-thalassaemia and Lepore mutations. Globin gene mapping studies indicated that the molecular lesion underlying delta beta-thalassaemia is a large deletion starting from the large intervening sequence of the delta gene and extending downstream from the beta gene. The possibility that delta beta-thalassaemia haplotypes in southern Italy originated from a single mutational event is discussed. Images PMID:6325696

  3. Hepatitis B (HBV)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Hepatitis B (HBV) KidsHealth > For Teens > Hepatitis B (HBV) A A A What's in this article? ... poisons). There are several different types of hepatitis . Hepatitis B is a type that can move from one ...

  4. Supersonic aerodynamics of delta wings

    NASA Technical Reports Server (NTRS)

    Wood, Richard M.

    1988-01-01

    Through the empirical correlation of experimental data and theoretical analysis, a set of graphs has been developed which summarize the inviscid aerodynamics of delta wings at supersonic speeds. The various graphs which detail the aerodynamic performance of delta wings at both zero-lift and lifting conditions were then employed to define a preliminary wing design approach in which both the low-lift and high-lift design criteria were combined to define a feasible design space.

  5. Treatment methods for the determination of delta2H and delta18O of hair keratin by continuous-flow isotope-ratio mass spectrometry.

    PubMed

    Bowen, Gabriel J; Chesson, Lesley; Nielson, Kristine; Cerling, Thure E; Ehleringer, James R

    2005-01-01

    The structural proteins that comprise approximately 90% of animal hair have the potential to record environmentally and physiologically determined variation in delta2H and delta18O values of body water. Broad, systematic, geospatial variation in stable hydrogen and oxygen isotopes of environmental water and the capacity for rapid, precise measurement via methods such as high-temperature conversion elemental analyzer/isotope ratio mass spectrometry (TC/EA-IRMS) make these isotope systems particularly well suited for applications requiring the geolocation of hair samples. In order for such applications to be successful, however, methods must exist for the accurate determination of hair delta2H and delta18O values reflecting the primary products of biosynthesis. Here, we present the results of experiments designed to examine two potential inaccuracies affecting delta2H and delta18O measurements of hair: the contribution of non-biologic hydrogen and oxygen to samples in the form of sorbed molecular water, and the exchange of hydroxyl-bound hydrogen between hair keratin and ambient water vapor. We show that rapid sorption of molecular water from the atmosphere can have a substantial effect on measured delta2H and delta18O values of hair (comprising approximately 7.7% of the measured isotopic signal for H and up to approximately 10.6% for O), but that this contribution can be effectively removed through vacuum-drying of samples for 6 days. Hydrogen exchange between hair keratin and ambient vapor is also rapid (reaching equilibrium within 3-4 days), with 9-16% of the total hydrogen available for exchange at room temperature. Based on the results of these experiments, we outline a recommended sample treatment procedure for routine measurement of delta2H and delta18O in mammal hair.

  6. Multiple virtual screening approaches for finding new Hepatitis c virus RNA-dependent RNA polymerase inhibitors: Structure-based screens and molecular dynamics for the pursue of new poly pharmacological inhibitors

    PubMed Central

    2012-01-01

    The RNA polymerase NS5B of Hepatitis C virus (HCV) is a well-characterised drug target with an active site and four allosteric binding sites. This work presents a workflow for virtual screening and its application to Drug Bank screening targeting the Hepatitis C Virus (HCV) RNA polymerase non-nucleoside binding sites. Potential polypharmacological drugs are sought with predicted active inhibition on viral replication, and with proven positive pharmaco-clinical profiles. The approach adopted was receptor-based. Docking screens, guided with contact pharmacophores and neural-network activity prediction models on all allosteric binding sites and MD simulations, constituted our analysis workflow for identification of potential hits. Steps included: 1) using a two-phase docking screen with Surflex and Glide Xp. 2) Ranking based on scores, and important H interactions. 3) a machine-learning target-trained artificial neural network PIC prediction model used for ranking. This provided a better correlation of IC50 values of the training sets for each site with different docking scores and sub-scores. 4) interaction pharmacophores-through retrospective analysis of protein-inhibitor complex X-ray structures for the interaction pharmacophore (common interaction modes) of inhibitors for the five non-nucleoside binding sites were constructed. These were used for filtering the hits according to the critical binding feature of formerly reported inhibitors. This filtration process resulted in identification of potential new inhibitors as well as formerly reported ones for the thumb II and Palm I sites (HCV-81) NS5B binding sites. Eventually molecular dynamics simulations were carried out, confirming the binding hypothesis and resulting in 4 hits. PMID:23282180

  7. In vivo neuronal co-expression of mu and delta opioid receptors uncovers new therapeutic perspectives

    PubMed Central

    Erbs, Eric; Faget, Lauren; Veinante, Pierre; Kieffer, Brigitte L; Massotte, Dominique

    2015-01-01

    Opioid receptors belong to the G protein coupled receptor family. They modulate brain function at all levels of neural integration and therefore impact on autonomous, sensory, emotional and cognitive processing. In vivo functional interaction between mu and delta opioid receptors are known to take place though it is still debated whether interactions occur at circuitry, cellular or molecular level. Also, the notion of receptor crosstalk via mu-delta heteromers is well documented in vitro but in vivo evidence remains scarce. To identify neurons in which receptor interactions could take place, we designed a unique double mutant knock-in mouse line that expresses functional red-fluorescent mu receptors and green-fluorescent delta receptors. We mapped mu and delta receptor distribution and co-localization throughout the nervous system and created the first interactive brain atlas with concomitant mu-delta visualization at subcellular resolution (http://mordor.ics-mci.fr/). Mu and delta receptors co-localize in neurons from subcortical networks but are mainly detected in separate neurons in the forebrain. Also, co-immunoprecipitation experiments indicated physical proximity in the hippocampus, a prerequisite to mu-delta heteromerization. Altogether, data suggest that mu-delta functional interactions take place at systems level for high-order emotional and cognitive processing whereas mu-delta may interact at cellular level in brain networks essential for survival, which has potential implications for innovative drug design in pain control, drug addiction and eating disorders. PMID:25938125

  8. In vivo neuronal co-expression of mu and delta opioid receptors uncovers new therapeutic perspectives.

    PubMed

    Erbs, Eric; Faget, Lauren; Veinante, Pierre; Kieffer, Brigitte L; Massotte, Dominique

    2014-09-01

    Opioid receptors belong to the G protein coupled receptor family. They modulate brain function at all levels of neural integration and therefore impact on autonomous, sensory, emotional and cognitive processing. In vivo functional interaction between mu and delta opioid receptors are known to take place though it is still debated whether interactions occur at circuitry, cellular or molecular level. Also, the notion of receptor crosstalk via mu-delta heteromers is well documented in vitro but in vivo evidence remains scarce. To identify neurons in which receptor interactions could take place, we designed a unique double mutant knock-in mouse line that expresses functional red-fluorescent mu receptors and green-fluorescent delta receptors. We mapped mu and delta receptor distribution and co-localization throughout the nervous system and created the first interactive brain atlas with concomitant mu-delta visualization at subcellular resolution (http://mordor.ics-mci.fr/). Mu and delta receptors co-localize in neurons from subcortical networks but are mainly detected in separate neurons in the forebrain. Also, co-immunoprecipitation experiments indicated physical proximity in the hippocampus, a prerequisite to mu-delta heteromerization. Altogether, data suggest that mu-delta functional interactions take place at systems level for high-order emotional and cognitive processing whereas mu-delta may interact at cellular level in brain networks essential for survival, which has potential implications for innovative drug design in pain control, drug addiction and eating disorders.

  9. Transmission of Hepatitis C Virus during Computed Tomography Scanning with Contrast

    PubMed Central

    Rius, Cristina; Caylà, Joan A.

    2008-01-01

    Six cases of acute hepatitis C related to computed tomography scanning with contrast were identified in 3 hospitals. A patient with chronic hepatitis C had been subjected to the same procedure immediately before each patient who developed acute infection. Viral molecular analysis showed identity between isolates from cases with acute and chronic hepatitis C. PMID:18258135

  10. Hepatitis Information for the Public

    MedlinePlus

    ... of Viral Hepatitis Contact Us 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 ...

  11. The DELTA Synchrotron Light Interferometer

    SciTech Connect

    Berges, U.

    2004-05-12

    Synchrotron radiation sources like DELTA, the Dortmund Electron Accelerator, a third generation synchrotron light source, need an optical monitoring system to measure the beam size at different points of the ring with high resolution and accuracy. These measurements also allow an investigation of the emittance of the storage ring, an important working parameter for the efficiency of working beamlines with experiments using the synchrotron radiation. The resolution limits of the different types of optical synchrotron light monitors at DELTA are investigated. The minimum measurable beamsize with the normal synchrotron light monitor using visible light at DELTA is about 80 {mu}m. Due to this a synchrotron light interferometer was built up and tested at DELTA. The interferometer uses the same beamline in the visible range. The minimum measurable beamsize is with about 8 {mu}m one order of magnitude smaller. This resolution is sufficient for the expected small vertical beamsizes at DELTA. The electron beamsize and emittance were measured with both systems at different electron beam energies of the storage ring. The theoretical values of the present optics are smaller than the measured emittance. So possible reasons for beam movements are investigated.

  12. Molecular analysis of the function of direct repeats and a polypurine tract for plus-strand DNA priming in woodchuck hepatitis virus.

    PubMed Central

    Seeger, C; Maragos, J

    1989-01-01

    The replication of the hepadnavirus DNA genome is initiated by reverse transcription of pregenome RNA into minus-strand DNA followed by plus-strand DNA synthesis. The priming of plus-strand DNA requires the transfer of an RNA primer from pregenome RNA to the primer-binding site on minus-strand DNA. Annealing of the primer to the primer-binding site is facilitated by short direct repeats, DR1 and DR2. To investigate the mechanism of plus-strand primer formation, we have introduced specific mutations into DR1 and DR2 and measured the effect of these mutants on initiation of plus-strand DNA synthesis. To facilitate such an analysis, we have constructed a vector for the efficient expression of woodchuck hepatitis virus in cultured cells. Our results suggest that the 3' end of the RNA primer is determined prior to its transfer to the primer-binding site and that the determination of the 3' end of the primer does not depend on a specific sequence motif at the cleavage site. In addition, we have identified an alternative initiation site for plus-strand DNA synthesis at a purine-rich sequence between DR1 and DR2. Initiation at this site occurs by a mechanism that is independent of the direct repeats and does not require the transfer of an RNA primer to the primer-binding site. Images PMID:2704069

  13. [Molecular characterization of hepatitis C virus in patients referred to a reference laboratory of public health, University Hospital "Antonio Patricio de Alcalá", Cumani, Venezuela].

    PubMed

    Sulbarán, María Zulay; Montaño, Lérida; Sulbarán, Yoneira; Loureiro, Carmen Luisa; Flores, Carmen Rosa; Farías, Yurviris; Maldonado, Antonio; Guillen, Genny; Rangel, Héctor; Pujol, Flor

    2016-03-01

    The World Health Organization estimates that approximately 170 million people are chronically infected with hepatitis C virus (HCV). This study evaluated the presence of antibodies against HCV by two immunoassays. HCV genotypes were analyzed by phylogenetic analysis of viral genome fragments amplified from the 5 'non-coding (5'NC) region and non-structural region 5b (NS5b), using reverse transcription and nested polymerase chain reaction (RT-PCR), in patients referred from January 2010 to February 2013 to the Reference Laboratory of Public Health, University Hospital "Antonio Patricio de Alcalá". The prevalence of anti-HCV antibodies was 0.57% (17/3005), being the group of patients older than 41 years the most affected (0.9%). A total of 16 samples were found positive for HCV RNA by RT-PCR in the 5'NC region (16/17, 94%). Phylogenetic analysis of the 5'NC region allowed to identify the circulation of genotypes 2 and 1, and one genotype 3 and one 4. By phylogenetic analysis of the NS5b region, diverse subtypes of HCV genotype 2 were identified (2a, 2j and 2s). This finding is in accordance with previous studies that indicate that this genotype is relatively diverse in our country.

  14. Chronic hepatitis B. Impact of hepatitis D virus superinfection and the hepatitis B e-system on histological outcome, and correlation of the hepatitis B e-system to HBV-DNA in serum.

    PubMed

    Lindh, G

    1986-01-01

    Chronic evolution after acute hepatitis B virus infection. During a 13 months period 1977-1978 a total of 129 cases of acute viral hepatitis type B occurred among patients who were admitted with hepatitis to Roslagstull, Hospital, Stockholm, Sweden. Less than 1% progressed to chronicity. Prevalence of Delta superinfection was studied among 60 patients with chronic hepatitis B. Nineteen (32%) were anti-delta positive. The majority of the positive patients were either non-European immigrants or addicts, both 9/19 (47%). Infections with the delta agent was found to have occurred in Stockholm already in the early 1970s. Rate of HBeAg clearance during chronic HBV was studied among 36 HBeAg positive patients. Seroconversion to anti-HBe was noted in 17 patients (47%), whereas HBeAg persisted in 19 during a mean follow-up period of 53 months. The spontaneous annual HBeAg seroconversion rate was 11%. HBeAg clearance occurred as frequently among homosexual men as among patients in other categories. However, 12/14 homosexual men were HBeAg positive after 2 years follow-up, compared with 1/13 drug addicts. Thus, homosexual men seemed to require a longer time for HBeAg seroconversion than i.v. drug addicts. HBV-DNA in serum, a strong indicator of viral particles and infectivity was analysed among patients with HBeAg seroconversion, initial HBeAg negativity and/or delta superinfection. HBV-DNA was found in 75-80% of our HBeAg positive patients. A correlation between chronic liver disease and presence of HBV-DNA in serum was also found. Thus, HBV DNA was found in 63% of patients with CAH or CAH/CI as compared with only 39% of patients with CPH. Delta infected patients had HBV-DNA more often than those without hepatitis D infection. Seven delta infected, anti-HBe positive, patients were still HBV-DNA positive five to eight years later. Therefore delta infected anti-HBe positive patients can be infectious for prolonged periods. Histological outcome. 63% (12/19) anti-delta positive

  15. Current and future hepatitis C therapies.

    PubMed

    Firpi, Roberto J; Nelson, David R

    2007-08-01

    Treatment of chronic hepatitis C patients has evolved significantly in the past 15 years. With a better knowledge of viral kinetics and molecular virology of the hepatitis C virus, we have gone from a low chance of viral eradication to a chance as high as 50%. Despite this, current therapies are not ideal and are associated with side effects, complications, and poor patient tolerability. Therefore, an urgent need to look for better strategies to treat this disease is imperative. Thanks to the current knowledge and ongoing research, we know the way we treat hepatitis C today will change dramatically in the next 5-10 years. This review will focus on current therapies for hepatitis C and the most recent advances in the search for new therapies.

  16. A proto-Okavango Delta?

    NASA Astrophysics Data System (ADS)

    Podgorski, J. E.; Kgotlhang, L.; Ngwisanyi, T.; Ploug, C.; Auken, E.; Kinzelbach, W. K.; Green, A. G.

    2010-12-01

    The Okavango Delta within the Kalahari Desert of northwestern Botswana is one of the world's largest inland deltas and the largest wetland in southern Africa. An annual flood originating from the Okavango River in the northwest passes through the upper panhandle region of the delta before inundating the 150 km x 150 km fan where most water is lost to evapotranspiration. The fan occupies an active graben at the southwestern end of the East Africa rift zone. The focus of faulting is along the fan’s southeastern end where the Kunyere-Thamalakane faults show 200-300 m of dip-slip offset, forming a backstop to the movement of water and sediments. An airborne TEM survey was flown over the entire delta in 2007 with 2 km line spacing. A preliminary inversion of the entire data set has been undertaken using a quasi-2D inversion scheme that includes resistivity, layer thickness, and transmitter height as parameters. Tests with a many-layer model indicate that a four-layer model explains the data. Inversion results are corroborated by limited borehole data. The TEM model includes significant lateral and vertical variations in electrical resistivity. In the central region of the fan, a near-surface high resistivity layer is underlain sequentially by a more conductive layer (about 100 m depth) and a more resistive half-space (about 160 m depth), the latter of which could be a fresh water aquifer. This resistive feature has a fan-like form. A plausible evolutionary scenario that explains the TEM data includes a proto-Okavango Delta (highly resistive half-space ) and a lake (intermediate-depth conductive layer). During a climatic episode similar to today’s, a proto-Okavango Delta sequence would have been deposited against a fault, much as the Kunyere-Thamalakane faults today delineate the southeastern margin of the present Okavango Delta. This region would have then been flooded by a Pleistocene lake system that inundated much of northern Botswana and was the source of

  17. Molecular Evolution and Genetic Analysis of the Major Capsid Protein VP1 of Duck Hepatitis A Viruses: Implications for Antigenic Stability.

    PubMed

    Ma, Xiuli; Sheng, Zizhang; Huang, Bing; Qi, Lihong; Li, Yufeng; Yu, Kexiang; Liu, Cunxia; Qin, Zhuoming; Wang, Dan; Song, Minxun; Li, Feng

    2015-01-01

    The duck hepatitis A virus (DHAV), a member of the family Picornaviridae, is the major cause of outbreaks with high mortality rates in young ducklings. It has three distinctive serotypes and among them, serotypes 1 (DHAV-1) and 3 (DHAV-3) were recognized in China. To investigate evolutionary and antigenic properties of the major capsid protein VP1 of these two serotypes, a primary target of neutralizing antibodies, we determined the VP1 coding sequences of 19 DHAV-1 (spanning 2000-2012) and 11 DHAV-3 isolates (spanning 2008-2014) associated with disease outbreaks. By bioinformatics analysis of VP1 sequences of these isolates and other DHAV strains reported previously, we demonstrated that DHAV-1 viruses evolved into two genetic lineages, while DHAV-3 viruses exhibited three distinct lineages. The rate of nucleotide substitution for DHAV-1 VP1 genes was estimated to be 5.57 x 10(-4) per site per year, which was about one-third times slower than that for DHAV-3 VP1 genes. The population dynamics analysis showed an upward trend for infection of DHAV-1 viruses over time with little change observed for DHAV-3 viruses. Antigenic study of representative DHAV-1 and DHAV-3 strains covering all observed major lineages revealed no detectable changes in viral neutralization properties within the serotype, despite the lack of cross-neutralization between serotypes 1 and 3 strains. Structural analysis identified VP1 mutations in DHAV-1 and DHAV-3 viruses that underpin the observed antigenic phenotypes. Results of our experiments described here shall give novel insights into evolution and antigenicity of duck picornaviruses.

  18. 3β-Hydroxysterol Δ24-Reductase on the Surface of Hepatitis C Virus-Related Hepatocellular Carcinoma Cells Can Be a Target for Molecular Targeting Therapy

    PubMed Central

    Saito, Makoto; Takano, Takashi; Nishimura, Tomohiro; Kohara, Michinori; Tsukiyama-Kohara, Kyoko

    2015-01-01

    In our previous study, we demonstrated that 3β-hydroxysterol Δ24-reductase (DHCR24) was overexpressed in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC), and that its expression was induced by HCV. Using a monoclonal antibody against DHCR24 (2-152a MAb), we found that DHCR24 was specifically expressed on the surface of HCC cell lines. Based on these findings, we aimed to establish a novel targeting strategy using 2-152a MAb to treat HCV-related HCC. In the present study, we examined the antitumor activity of 2-152a MAb. In the presence of complement, HCC-derived HuH-7 cells were killed by treatment with 2-152a MAb, which was mediated by complement-dependent cytotoxicity (CDC). In addition, the antigen recognition domain of 2-152a MAb was responsible for the unique anti-HCV activity. These findings demonstrate the feasibility of using 2-152a MAb for antibody therapy against HCV-related HCC. In addition, surface DHCR24 on HCC cells exhibited a functional property, agonist-induced internalization. We showed that 2-152a MAb-mediated binding of a cytotoxic agent (a saponin-conjugated secondary antibody) to surface DHCR24 led to significant cytotoxicity. This suggests that surface DHCR24 on HCC cells can function as a carrier for internalization. Therefore, surface DHCR24 could be a valuable target for HCV-related HCC therapy, and 2-152a MAb appears to be useful for this targeted therapy. PMID:25875901

  19. Identification of European-type hepatitis E virus subtype 3e isolates in Japanese wild boars: molecular tracing of HEV from swine to wild boars.

    PubMed

    Nakano, Tatsunori; Takahashi, Kazuaki; Arai, Masahiro; Okano, Hiroshi; Kato, Hideaki; Ayada, Minoru; Okamoto, Hiroaki; Mishiro, Shunji

    2013-08-01

    Nucleotide sequences of hepatitis E virus (HEV) isolates infecting wild boars in Mie prefecture, which is located in the central region of Japan and is far from the most prevalent regions of HEV infection in Japan, were determined and characterised. Among 144 serum samples of wild boars captured in Mie prefecture, 7 were positive for HEV-RNA. The nucleotide sequence of nearly the entire genome was determined for 4 of the 7 positive samples. Phylogenetic tree analyses indicated that 6 samples were subtype 3e and 1 was subtype 3a among the 7 isolates. We identified the indigenization of subtype 3e isolates in Japanese wild boars. Furthermore, 5 subtype 3e isolates were closely related and were located in the peripheral branch of subtype 3e isolates from European countries in the phylogenetic tree. The structure indicated that the ancestor of the 5 subtype 3e isolates originated in Europe. The phylogenetic structure and coalescent analyses suggested that the subtype 3e isolates entered Japan from Europe by importation of large-race pigs around 1966. The results also indicated that several lineages of subtype 3e expanded to a wide area of Japan around 1992 and 1 of the lineages was indigenized in wild boars in Mie prefecture between 1992 and 2009. The appearance of a wild boar cluster in the peripheral branch in the phylogenetic lineage may indicate the direction of gene flow of HEV subtype 3e from swine to wild boars. Clarification of the transmission direction or route should be helpful to prevent a future endemic or epidemic of HEV infection.

  20. Molecular and structural basis for the roles of hepatitis C virus polymerase NS5B amino acids 15, 223, and 321 in viral replication and drug resistance.

    PubMed

    Lam, Angela M; Edwards, Thomas E; Mosley, Ralph T; Murakami, Eisuke; Bansal, Shalini; Lugo, Christopher; Bao, Haiying; Otto, Michael J; Sofia, Michael J; Furman, Phillip A

    2014-11-01

    Resistance to the 2'-F-2'-C-methylguanosine monophosphate nucleotide hepatitis C virus (HCV) inhibitors PSI-352938 and PSI-353661 was associated with a combination of amino acid changes (changes of S to G at position 15 [S15G], C223H, and V321I) within the genotype 2a nonstructural protein 5B (NS5B), an RNA-dependent RNA polymerase. To understand the role of these residues in viral replication, we examined the effects of single and multiple point mutations on replication fitness and inhibition by a series of nucleotide analog inhibitors. An acidic residue at position 15 reduced replicon fitness, consistent with its proximity to the RNA template. A change of the residue at position 223 to an acidic or large residue reduced replicon fitness, consistent with its proposed proximity to the incoming nucleoside triphosphate (NTP). A change of the residue at position 321 to a charged residue was not tolerated, consistent with its position within a hydrophobic cavity. This triple resistance mutation was specific to both genotype 2a virus and 2'-F-2'-C-methylguanosine inhibitors. A crystal structure of the NS5B S15G/C223H/V321I mutant of the JFH-1 isolate exhibited rearrangement to a conformation potentially consistent with short primer-template RNA binding, which could suggest a mechanism of resistance accomplished through a change in the NS5B conformation, which was better tolerated by genotype 2a virus than by viruses of other genotypes.

  1. Different molecular mechanisms of inhibition of bovine viral diarrhea virus and hepatitis C virus RNA-dependent RNA polymerases by a novel benzimidazole.

    PubMed

    Asthana, Shailendra; Shukla, Saumya; Vargiu, Attilio V; Ceccarelli, Matteo; Ruggerone, Paolo; Paglietti, Giuseppe; Marongiu, Maria E; Blois, Sylvain; Giliberti, Gabriele; La Colla, Paolo

    2013-05-28

    The virus-encoded RNA-dependent RNA polymerase (RdRp) has emerged as a primary target in the search for selective inhibitors of Flaviviridae. Recently, we reported on the selective inhibition, in cell-based assays, of both BVDV (EC50 = 0.80 ± 0.06 μM) and HCV (EC50 = 1.11 ± 0.15 μM) by 2-{1-[2-(2,4-dimethoxyphenyl)-1H-benzimidazol-5-yl]ethylidene}hydrazinecarbothioamide (227G). Here we show that, in enzyme assays with recombinant enzymes, 227G inhibits, in a dose-dependent manner, the RdRp of both BVDV (IC50 = 0.0020 ± 0.0004 μM) and HCV (IC50 = 0.40 ± 0.04 μM). Furthermore, we report on the selection and molecular analysis of a BVDV-resistant mutant, characterized by the presence of the I261M mutation. By applying a multilevel computational approach, we identified different 227G binding sites on the two RdRps. They were further validated by the good agreement between the calculated affinities and those extrapolated from IC50 values. Our findings suggest different molecular mechanisms of inhibition of the HCV and BVDV RdRps by 227G and indicate the importance of understanding ligand-enzyme interactions at the molecular level for the rational design of new and more potent leads.

  2. Hemostasis and Hepatic Surgery.

    PubMed

    Eeson, Gareth; Karanicolas, Paul J

    2016-04-01

    Operative blood loss is a major source of morbidity and even mortality for patients undergoing hepatic resection. This review discusses strategies to minimize blood loss and the utilization of allogeneic blood transfusion pertaining to oncologic hepatic surgery.

  3. Know More Hepatitis

    MedlinePlus

    ... Boomers Hepatitis Risk Assessment Campaign Materials Fact Sheets Posters Infographics Videos Buttons & Badges Email Signatures Radio Ads and Scripts Know More Hepatitis Logos Presentation Templates Guidelines for using materials and logos About ...

  4. Hepatitis A - children

    MedlinePlus

    ... hepatitis A. Children can get hepatitis A at day care center from other children or from child care ... treatment with immunoglobulin therapy. If your child attends day care: Make sure the children and staff at the ...

  5. Hepatic (Liver) Function Panel

    MedlinePlus

    ... related side effects. The hepatic function panel evaluates: Alanine aminotransferase (ALT). This enzyme, found in the liver, ... MORE ON THIS TOPIC Mononucleosis Hepatitis Blood Test: Alanine Aminotransferase (ALT, or SGPT) Blood Test: Aspartate Aminotransferase ( ...

  6. Hepatitis Foundation International

    MedlinePlus

    ... million people globally. admin / 03/17/2015 Viral Hepatitis An estimated 4.4 million Americans from all ... Events section below. EVENTS FULL CALENDAR Loading… VIRAL HEPATITIS DISPARITIES HARD TO REACH, HARD TO TREAT™ AFRICAN ...

  7. Hepatitis virus panel

    MedlinePlus

    ... 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 ...

  8. Hepatitis B -- children

    MedlinePlus

    ... at birth: Newborn babies should receive their first hepatitis B vaccine and one dose of immunoglobulins (IG) within 12 hours. The baby should complete all hepatitis B vaccines as recommended during the first six months. Some ...

  9. Hepatitis B (HBV)

    MedlinePlus

    ... special immune injection and the first dose of hepatitis B vaccine at birth. How Is It Prevented? Because people ... B virus. Doctors recommend that teens get a hepatitis B immunization (vaccine). It's a series of three shots over a ...

  10. Hepatitis C (image)

    MedlinePlus

    Hepatitis C is a virus-caused liver inflammation which may cause jaundice, fever and cirrhosis. Persons who are most at risk for contracting and spreading hepatitis C are those who share needles for injecting drugs ...

  11. Hepatitis E Pathogenesis

    PubMed Central

    Lhomme, Sébastien; Marion, Olivier; Abravanel, Florence; Chapuy-Regaud, Sabine; Kamar, Nassim; Izopet, Jacques

    2016-01-01

    Although most hepatitis E virus (HEV) infections are asymptomatic, some can be severe, causing fulminant hepatitis and extra-hepatic manifestations, including neurological and kidney injuries. Chronic HEV infections may also occur in immunocompromised patients. This review describes how our understanding of the pathogenesis of HEV infection has progressed in recent years. PMID:27527210

  12. What Is Hepatitis?

    MedlinePlus

    ... عربي 中文 English Français Русский Español What is hepatitis? Online Q&A Reviewed July 2016 Q: What ... Question and answer archives Submit a question World Hepatitis Day Know hepatitis - Act now Event notice Key ...

  13. Stable isotope deltas: tiny, yet robust signatures in nature.

    PubMed

    Brand, Willi A; Coplen, Tyler B

    2012-09-01

    Although most of them are relatively small, stable isotope deltas of naturally occurring substances are robust and enable workers in anthropology, atmospheric sciences, biology, chemistry, environmental sciences, food and drug authentication, forensic science, geochemistry, geology, oceanography, and paleoclimatology to study a variety of topics. Two fundamental processes explain the stable isotope deltas measured in most terrestrial systems: isotopic fractionation and isotope mixing. Isotopic fractionation is the result of equilibrium or kinetic physicochemical processes that fractionate isotopes because of small differences in physical or chemical properties of molecular species having different isotopes. It is shown that the mixing of radioactive and stable isotope end members can be modelled to provide information on many natural processes, including (14)C abundances in the modern atmosphere and the stable hydrogen and oxygen isotopic compositions of the oceans during glacial and interglacial times. The calculation of mixing fractions using isotope balance equations with isotope deltas can be substantially in error when substances with high concentrations of heavy isotopes (e.g. (13)C, (2)H, and (18)O ) are mixed. In such cases, calculations using mole fractions are preferred as they produce accurate mixing fractions. Isotope deltas are dimensionless quantities. In the International System of Units (SI), these quantities have the unit 1 and the usual list of prefixes is not applicable. To overcome traditional limitations with expressing orders of magnitude differences in isotope deltas, we propose the term urey (symbol Ur), after Harold C. Urey, for the unit 1. In such a manner, an isotope delta value expressed traditionally as-25 per mil can be written as-25 mUr (or-2.5 cUr or-0.25 dUr; the use of any SI prefix is possible). Likewise, very small isotopic differences often expressed in per meg 'units' are easily included (e.g. either+0.015 ‰ or+15 per meg

  14. Stable isotope deltas: Tiny, yet robust signatures in nature

    USGS Publications Warehouse

    Brand, Willi A.; Coplen, Tyler B.

    2012-01-01

    Although most of them are relatively small, stable isotope deltas of naturally occurring substances are robust and enable workers in anthropology, atmospheric sciences, biology, chemistry, environmental sciences, food and drug authentication, forensic science, geochemistry, geology, oceanography, and paleoclimatology to study a variety of topics. Two fundamental processes explain the stable isotope deltas measured in most terrestrial systems: isotopic fractionation and isotope mixing. Isotopic fractionation is the result of equilibrium or kinetic physicochemical processes that fractionate isotopes because of small differences in physical or chemical properties of molecular species having different isotopes. It is shown that the mixing of radioactive and stable isotope end members can be modelled to provide information on many natural processes, including 14C abundances in the modern atmosphere and the stable hydrogen and oxygen isotopic compositions of the oceans during glacial and interglacial times. The calculation of mixing fractions using isotope balance equations with isotope deltas can be substantially in error when substances with high concentrations of heavy isotopes (e.g. 13C, 2H, and 18O ) are mixed. In such cases, calculations using mole fractions are preferred as they produce accurate mixing fractions. Isotope deltas are dimensionless quantities. In the International System of Units (SI), these quantities have the unit 1 and the usual list of prefixes is not applicable. To overcome traditional limitations with expressing orders of magnitude differences in isotope deltas, we propose the term urey (symbol Ur), after Harold C. Urey, for the unit 1. In such a manner, an isotope delta value expressed traditionally as−25 per mil can be written as−25 mUr (or−2.5 cUr or−0.25 dUr; the use of any SI prefix is possible). Likewise, very small isotopic differences often expressed in per meg ‘units’ are easily included (e.g. either+0.015 ‰ or+15 per meg

  15. Hepatitis C.

    PubMed

    Burra, Patrizia

    2009-02-01

    Hepatitis C virus (HCV) is a leading cause of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. HCV nearly always recurs in liver-transplanted patients, and 10 to 25% of them develop cirrhosis within 5 to 10 years. One of the strategies suggested to limit virological HCV recurrence is pretransplant antiviral treatment, but studies are warranted on the pharmacokinetics of antiviral drugs in cirrhotic patients, the benefits of fixed or escalating antiviral drug dosage schedules, the duration of the treatment, and the indications for using growth factors. Several risk factors are associated with a more aggressive recurrent HCV and early allograft failure, such as an older donor age. The relationship between immunosuppression and fibrosis progression in HCV recurrence remains uncertain. Concerning the antiviral treatment, treating established recurrent disease with a combination of interferon and ribavirin has been the mainstay of management to date, but when it is best to start and how to manage the side effects are still controversial issues. Antiviral treatment should be started once the disease has been confirmed by a biopsy when the fibrosis develops, providing that ongoing acute or chronic rejection, biliary obstruction, vascular damage, autoimmune diseases and sepsis, and any other standard contraindications for antiviral therapy, have been excluded. HCV recurrence after liver transplantation may well lead to graft failure and become an indication for retransplantation, but this is done in a relatively small number of cases, accounting for only 3 to 5% of retransplanted patients, since retransplantation is associated with much worse results than primary liver transplant procedures. We must be prepared for the fact that increasing numbers of HCV-positive recipients with allografts failing due to recurrent HCV will be asking to be retransplanted-and we do not know yet how to respond to this

  16. Design of lipid-based delivery systems for improving lymphatic transport and bioavailability of delta-tocopherol and nobiletin

    NASA Astrophysics Data System (ADS)

    Xia, Chunxin

    Lymphatic drug transport can confer bioavailability advantage by avoiding the first-pass metabolism normally observed in the portal vein hepatic route. It was reported that long chain lipid-based delivery systems can stimulate the formation of chylomicron and thus promote the lymphatic transport of drugs. In this study, a novel delta-tocopherol (delta-T) loaded Solid Lipid Nanoparticle (SLN) system was developed to investigate its effect on promoting the lymphatic transport of delta-T. The delta-T SLN was prepared with hot melt emulsification method by using glyceryl behenate (compritol RTM888) as the lipid phase and lecithin (PC75) as the emulsifier. Formula configuration, processing condition and loading capacity were carefully optimized. Physicochemical properties (particle size, surface charge, morphology) were also characterized. Moreover, excellent stability of the developed delta-T SLN in the gastrointestinal environment was observed by using an in vitro digestion model. Further investigations of the SLN in stimulating delta-T lymphatic transport were performed on mice without cannulation. Compared with the control group (delta-T corn oil dispersion), much lower delta-T levels in both blood and liver indicated reduced portal vein and hepatic transport of delta-T in the form of SLN. On the other hand, significantly higher concentrations of delta-T were observed in thymus, a major lymphatic tissue, indicating improved lymphatic transport of delta-T with the SLN delivery system. Finally, the far less excreted delta-T level in feces further confirmed improved lymphatic transport and overall bioavailability of delta-T by using SLN system. Nobiletin (NOB), one of most abundant polymethoxyflavones (PMFs) found in Citrus genus, has a low solubility in both water and oil at ambient temperatures. Thus it tends to form crystals when the loading exceeds its saturation level in the carrier system. This character greatly impaired its bioavailability and application. To

  17. Delta launch vehicle inertial guidance system (DIGS)

    NASA Technical Reports Server (NTRS)

    Duck, K. I.

    1973-01-01

    The Delta inertial guidance system, part of the Delta launch vehicle improvement effort, has been flown on three launches and was found to perform as expected for a variety of mission profiles and vehicle configurations.

  18. Revisiting double Dirac delta potential

    NASA Astrophysics Data System (ADS)

    Ahmed, Zafar; Kumar, Sachin; Sharma, Mayank; Sharma, Vibhu

    2016-07-01

    We study a general double Dirac delta potential to show that this is the simplest yet still versatile solvable potential to introduce double wells, avoided crossings, resonances and perfect transmission (T = 1). Perfect transmission energies turn out to be the critical property of symmetric and anti-symmetric cases wherein these discrete energies are found to correspond to the eigenvalues of a Dirac delta potential placed symmetrically between two rigid walls. For well(s) or barrier(s), perfect transmission (or zero reflectivity, R(E)) at energy E=0 is non-intuitive. However, this has been found earlier and called the ‘threshold anomaly’. Here we show that it is a critical phenomenon and we can have 0≤slant R(0)\\lt 1 when the parameters of the double delta potential satisfy an interesting condition. We also invoke a zero-energy and zero curvature eigenstate (\\psi (x)={Ax}+B) of the delta well between two symmetric rigid walls for R(0)=0. We resolve that the resonant energies and the perfect transmission energies are different and they arise differently.

  19. N-{Delta} weak transition

    SciTech Connect

    Graczyk, Krzysztof M.

    2011-11-23

    A short review of the Rein-Sehgal and isobar models is presented. The attention is focused on the nucleon-{Delta}(1232) weak transition form-factors. The results of the recent re-analyses of the ANL and BNL bubble chamber neutrino-deuteron scattering data are discussed.

  20. Delta-ALA urine test

    MedlinePlus

    ... increased level of urinary delta-ALA may indicate: Lead poisoning Porphyria (several types) A decreased level may occur ... A.M. Editorial team. Related MedlinePlus Health Topics Lead Poisoning Porphyria Browse the Encyclopedia A.D.A.M., ...

  1. Spongeplant Spreading in the Delta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Invasive, exotic aquatic plants impact a range of important economic and ecological functions in the Sacramento-San Joaquin Delta of California, and the state now spends over $5 million to control water hyacinth and Brazilian waterweed. In 2007, a new exotic floating plant South American Spongeplan...

  2. Phytoplankton fuels Delta food web

    USGS Publications Warehouse

    Jassby, Alan D.; Cloern, James E.; Muller-Solger, A. B.

    2003-01-01

    Populations of certain fishes and invertebrates in the Sacramento-San Joaquin Delta have declined in abundance in recent decades and there is evidence that food supply is partly responsible. While many sources of organic matter in the Delta could be supporting fish populations indirectly through the food web (including aquatic vegetation and decaying organic matter from agricultural drainage), a careful accounting shows that phytoplankton is the dominant food source. Phytoplankton, communities of microscopic free-floating algae, are the most important food source on a Delta-wide scale when both food quantity and quality are taken into account. These microscopic algae have declined since the late 1960s. Fertilizer and pesticide runoff do not appear to be playing a direct role in long-term phytoplankton changes; rather, species invasions, increasing water transparency and fluctuations in water transport are responsible. Although the potential toxicity of herbicides and pesticides to plank- ton in the Delta is well documented, the ecological significance remains speculative. Nutrient inputs from agricultural runoff at current levels, in combination with increasing transparency, could result in harmful al- gal blooms. 

  3. [Epidemiology of viral hepatitis].

    PubMed

    Kaić, Bernard; Vilibić-Cavlek, Tatjana; Filipović, Sanja Kurecić; Nemeth-Blazić, Tatjana; Pem-Novosel, Iva; Vucina, Vesna Visekruna; Simunović, Aleksandar; Zajec, Martina; Radić, Ivan; Pavlić, Jasmina; Glamocanin, Marica; Gjenero-Margan, Ira

    2013-10-01

    Understanding the country-specific epidemiology of disease, which may vary greatly among countries, is crucial for identifying the most appropriate preventive and control measures. An overview of the local epidemiology of viral hepatitis in Croatia is given in this paper. The overall prevalence of hepatitis B in Croatia is low (less than 2% HBsAg carriers in the general population). Hepatitis B incidence and prevalence began to decline significantly following the introduction of universal hepatitis B vaccination in 1999. Information on HBsAg seroprevalence is derived from routine testing of certain subpopulations (pregnant women, blood donors) and seroprevalence studies mostly targeted at high-risk populations. Universal childhood vaccination against hepatitis B remains the main preventive measure. We recommend testing for immunity one to two months after the third dose of hepatitis B vaccine for health-care workers. The incidence and prevalence of hepatitis C have also been declining in the general population. The main preventive measures are ensuring safety of blood products, prevention of drug abuse, and harm reduction programs for intravenous drug users. Hepatitis A incidence has declined dramatically since fifty years ago, when thousands of cases were reported annually. In the last five years, an average of twenty cases have been reported per year. The reduction of hepatitis A is a consequence of improved personal and community hygiene and sanitation. Hepatitis D has not been reported in Croatia. The risk of hepatitis D will get to be even smaller as the proportion of population vaccinated against hepatitis B builds up. Hepatitis E is reported only sporadically in Croatia, mostly in persons occupationally in contact with pigs and in travelers to endemic countries. In conclusion, Croatia is a low prevalence country for hepatitides A, B and C. Hepatitis D has not been reported to occur in Croatia and there are only sporadic cases of hepatitis E. Since hepatitis

  4. Synthesis of hepatic lipase in liver and extrahepatic tissues

    SciTech Connect

    Doolittle, M.H.; Wong, H.; Davis, R.C.; Schotz, M.C.

    1987-11-01

    Immunoprecipitations of hepatic lipase from pulse-labeled rat liver have demonstrated that hepatic lipase is synthesized in two distinct molecular weight forms, HL-I (Mr = 51,000) and HL-II (Mr = 53,000). Both forms are immunologically related to purified hepatic lipase, but not to lipoprotein lipase. HL-I and HL-II are also kinetically related and represent different stages of intracellular processing. Glycosidase experiments suggest that HL-I is the high mannose microsomal form of the mature, sialylated HL-II enzyme. Hepatic lipase activity was detected in liver and adrenal gland but was absent in brain, heart, kidney, testes, small intestine, lung, and spleen. The adrenal and liver lipase activities were inhibited in a similar dose-dependent manner by hepatic lipase antiserum. Immunoblot analysis of partially purified adrenal lipase showed an immunoreactive band co-migrating with HL-II at 53,000 daltons which was absent in a control blot treated with preimmune serum. Adrenal lipase and authentic hepatic lipase yielded similar peptide maps, confirming the presence of the lipase in adrenal gland. However, incorporation of L-(/sup 35/S)methionine into immunoprecipitable hepatic lipase was not detected in this tissue. In addition, Northern blot analysis showed the presence of hepatic lipase mRNA in liver but not adrenal gland. The presence of hepatic lipase in adrenal gland in the absence of detectable synthesis or messenger suggests that hepatic lipase originates in liver and is transported to this extrahepatic site.

  5. Protein Kinase C-{delta} mediates down-regulation of heterogeneous nuclear ribonucleoprotein K protein: involvement in apoptosis induction

    SciTech Connect

    Gao, Feng-Hou; Wu, Ying-Li; Zhao, Meng; Chen, Guo-Qiang

    2009-11-15

    We reported previously that NSC606985, a camptothecin analogue, induces apoptosis of acute myeloid leukemia (AML) cells through proteolytic activation of protein kinase C delta ({Delta}PKC-{delta}). By subcellular proteome analysis, heterogeneous nuclear ribonucleoprotein K (hnRNP K) was identified as being significantly down-regulated in NSC606985-treated leukemic NB4 cells. HnRNP K, a docking protein for DNA, RNA, and transcriptional or translational molecules, is implicated in a host of processes involving the regulation of gene expression. However, the molecular mechanisms of hnRNP K reduction and its roles during apoptosis are still not understood. In the present study, we found that, following the appearance of the {Delta}PKC-{delta}, hnRNP K protein was significantly down-regulated in NSC606985, doxorubicin, arsenic trioxide and ultraviolet-induced apoptosis. We further provided evidence that {Delta}PKC-{delta} mediated the down-regulation of hnRNP K protein during apoptosis: PKC-{delta} inhibitor could rescue the reduction of hnRNP K; hnRNP K failed to be decreased in PKC-{delta}-deficient apoptotic KG1a cells; conditional induction of {Delta}PKC-{delta} in U937T cells directly down-regulated hnRNP K protein. Moreover, the proteasome inhibitor also inhibited the down-regulation of hnRNP K protein by apoptosis inducer and the conditional expression of {Delta}PKC-{delta}. More intriguingly, the suppression of hnRNP K with siRNA transfection significantly induced apoptosis. To our knowledge, this is the first demonstration that proteolytically activated PKC-{delta} down-regulates hnRNP K protein in a proteasome-dependent manner, which plays an important role in apoptosis induction.

  6. Hepatitis E: an emerging disease.

    PubMed

    Pérez-Gracia, María Teresa; Suay, Beatriz; Mateos-Lindemann, María Luisa

    2014-03-01

    Currently, the infection with the hepatitis E virus represents the most frequent cause for acute hepatitis and jaundice in the world. According to WHO estimations, around two billion people, representing one third of the world's population, live in endemic areas for HEV and, therefore, are at risk of infection. In developed countries, the circulation of the virus in both human and animal (swine, boar, deer) sewage has been confirmed; however, the incidence rate is low compared to that of developing countries where outbreaks of acute hepatitis transmitted via the fecal-oral route are originated, more frequently in the flooding season or after natural disasters, combined with deficient sanitary conditions. There are currently 4 known genotypes of HEV. Genotypes 1 and 2 are isolated in all human epidemic outbreaks in developing countries, while genotypes 3 and 4 are isolated not only in humans but also in animals, in both developing and industrialized countries. These data support genotypes 3 and 4 having zoonotic nature. The diagnosis of this disease is based in the detection of anti-HEV IgG and IgM in blood serum using enzyme-linked immunosorbent methods. However, the method that best confirms the diagnosis is the RT-PCR, which detects HEV RNA in blood serum and also provides the genotype. The clinical course is generally that of an acute hepatitis which in some cases may require hospitalization and that, in transplant patients or HIV infected individuals can become a chronic hepatitis. Furthermore, the virus constitutes an important risk for pregnant women. The hepatitis E can present a wide range of symptoms, from a subclinical case to chronic liver disease with extrahepatic manifestations. For this reason, the diagnostic is challenging if no differential diagnosis is included. There is no specific antiviral drug for hepatitis E, but satisfactory results have been observed in some patients treated with pegylated interferon alfa2a and/or ribavirin. This revision is

  7. Maintenance of large deltas through channelization

    NASA Astrophysics Data System (ADS)

    Giosan, L.; Constatinescu, S.; Filip, F.

    2013-12-01

    A new paradigm for delta restoration is currently taking shape using primarily Mississippi delta examples. Here we propose an alternative for delta maintenance primarily envisioned for wave-influenced deltas based on Danube delta experiences. Over the last half century, while the total sediment load of the Danube dramatically decreased due to dam construction on tributaries and its mainstem, a grand experiment was inadvertently run in the Danube delta: the construction of a dense network of canals, which almost tripled the water discharge toward the interior of the delta plain. We use core-based and chart-based sedimentation rates and patterns to explore the delta transition from the natural to an anthropogenic regime, to understand the effects of far-field damming and near-field channelization, and to construct a conceptual model for delta development as a function sediment partition between the delta plain and the delta coastal fringe. We show that sediment fluxes increased to the delta plain due to channelization, counteracting sea level rise. In turn, the delta coastal fringe was most impacted by the Danube's sediment load collapse. Furthermore, we show that morphodynamic feedbacks at the river mouth are crucial in trapping sediment near the coast and constructing wave-dominated deltas or lobes or delaying their destruction. As a general conclusion, we suggest that increased channelization that mimics and enhances natural processes may provide a simple solution for keeping delta plains above sea level and that abandonment of wave-dominated lobes may be the most long term efficient solution for protecting the internal fluvial regions of deltas and provide new coastal growth downcoast.

  8. Quantitative structure-activity relationship and molecular docking revealed a potency of anti-hepatitis C virus drugs against human corona viruses.

    PubMed

    Elfiky, Abdo A; Mahdy, Samah M; Elshemey, Wael M

    2016-11-19

    A number of human coronaviruses (HCoVs) were reported in the last and present centuries. Some outbreaks of which (eg, SARS and MERS CoVs) caused the mortality of hundreds of people worldwide. The problem of finding a potent drug against HCoV strains lies in the inability of finding a drug that stops the viral replication through inhibiting its important proteins. In spite of its limited efficacy and potential side effects, Ribavirin is extensively used as a first choice against HCoVs. Therefore, scientists reverted towards the investigation of different drugs that can more specifically target proteins. In this study, four anti-HCV drugs (one approved by FDA and others under clinical trials) are tested against HCoV polymerases. Quantitative Structure-Activity Relationship (QSAR) and molecular docking are both used to compare the performance of the selected nucleotide inhibitors to their parent nucleotides and Ribavirin. Both QSAR and molecular docking showed that IDX-184 is superior compared to Ribavirin against MERS CoV, a result that was also reported for HCV. MK-0608 showed a performance that is comparable to Ribavirin. We strongly suggest an in vitro study on the potency of these two drugs against MERS CoV.

  9. Limited junctional diversity of V delta 5-J delta 1 rearrangement in multiple sclerosis patients.

    PubMed

    Nowak, J S; Michałowska-Wender, G; Januszkiewicz, D; Wender, M

    1997-01-01

    T-cell receptor (TCR) delta gene repertoire, as assessed by V delta-J delta rearrangements, has been analyzed in nine multiple sclerosis (MS) cases and in 30 healthy individuals by seminested PCR technique. Among the V delta-J delta junctional diversities studied, the most striking result has been observed in V delta 5-J delta 1 rearrangement. The detection of repeated V delta 5-J delta 1 nucleotide sequences in all analyzed clones from seven out of nine patients studied proved the monoclonal nature of gamma delta T-cells with V delta 5-J delta 1 rearrangement. The clonal nature of this rearrangement proved by PAGE and sequencing analysis may suggest an antigen-driven expansion of gamma delta T cells and argues for a significant role of gamma delta T-cells with V delta 5-J delta 1 rearrangement in MS pathogenesis. However, it cannot be excluded that clonal expansion of these lymphocytes may represent secondary change to central nervous system damage.

  10. High prevalence of occult hepatitis B virus genotype H infection among children with clinical hepatitis in west Mexico.

    PubMed

    Escobedo-Melendez, Griselda; Panduro, Arturo; Fierro, Nora A; Roman, Sonia

    2014-09-01

    Studies on the prevalence of infection with hepatitis B virus (HBV) among children are scarce in Latin American countries, especially in Mexico. This study was aimed to investigate the prevalence of HBV infection, occult hepatitis B infection (OBI) and HBV genotypes among children with clinical hepatitis. In total, 215 children with clinical hepatitis were evaluated for HBV infection. HBV serological markers and HBV DNA were analysed. OBI diagnosis and HBV genotyping was performed. HBV infection was found in 11.2% of children with clinical hepatitis. Among these HBV DNA positive-infected children, OBI was identified in 87.5% (n = 21/24) of the cases and 12.5% (n = 3/24) were positive for both HBV DNA and hepatitis B surface antigen. OBI was more frequent among children who had not been vaccinated against hepatitis B (p < 0.05) than in those who had been vaccinated. HBV genotype H was prevalent in 71% of the children followed by genotype G (8%) and genotype A (4%). In conclusion, OBI is common among Mexican children with clinical hepatitis and is associated with HBV genotype H. The results show the importance of the molecular diagnosis of HBV infection in Mexican paediatric patients with clinical hepatitis and emphasise the necessity of reinforcing hepatitis B vaccination in children.

  11. 27 CFR 9.96 - Mississippi Delta.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Mississippi Delta. 9.96... Mississippi Delta. (a) Name. The name of the viticultural area described in this section is “Mississippi Delta.” (b) Approved maps. The appropriate maps for determining the boundaries of the Mississippi...

  12. 27 CFR 9.96 - Mississippi Delta.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Mississippi Delta. 9.96... Mississippi Delta. (a) Name. The name of the viticultural area described in this section is “Mississippi Delta.” (b) Approved maps. The appropriate maps for determining the boundaries of the Mississippi...

  13. 27 CFR 9.96 - Mississippi Delta.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Mississippi Delta. 9.96... Mississippi Delta. (a) Name. The name of the viticultural area described in this section is “Mississippi Delta.” (b) Approved maps. The appropriate maps for determining the boundaries of the Mississippi...

  14. 27 CFR 9.96 - Mississippi Delta.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Mississippi Delta. 9.96... Mississippi Delta. (a) Name. The name of the viticultural area described in this section is “Mississippi Delta.” (b) Approved maps. The appropriate maps for determining the boundaries of the Mississippi...

  15. 27 CFR 9.96 - Mississippi Delta.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Mississippi Delta. 9.96... Mississippi Delta. (a) Name. The name of the viticultural area described in this section is “Mississippi Delta.” (b) Approved maps. The appropriate maps for determining the boundaries of the Mississippi...

  16. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of thiazolone derivatives as hepatitis C virus NS5B polymerase allosteric inhibitors

    NASA Astrophysics Data System (ADS)

    Lei, Beilei; Du, Juan; Li, Shuyan; Liu, Huanxiang; Ren, Yueying; Yao, Xiaojun

    2008-10-01

    Three-dimensional quantitative structure-activity relationship (3D-QSAR) models for a series of thiazolone derivatives as novel inhibitors bound to the allosteric site of hepatitis C virus (HCV) NS5B polymerase were developed based on CoMFA and CoMSIA analyses. Two different conformations of the template molecule and the combinations of different CoMSIA field/fields were considered to build predictive CoMFA and CoMSIA models. The CoMFA and CoMSIA models with best predictive ability were obtained by the use of the template conformation from X-ray crystal structures. The best CoMFA and CoMSIA models gave q 2 values of 0.621 and 0.685, and r 2 values of 0.950 and 0.940, respectively for the 51 compounds in the training set. The predictive ability of the two models was also validated by using a test set of 16 compounds which gave r pred 2 values of 0.685 and 0.822, respectively. The information obtained from the CoMFA and CoMSIA 3D contour maps enables the interpretation of their structure-activity relationship and was also used to the design of several new inhibitors with improved activity.

  17. Circulation of genotype-I hepatitis B virus in the primitive tribes of Arunachal Pradesh in early sixties and molecular evolution of genotype-I.

    PubMed

    Haldipur, Bangari P; Walimbe, Atul M; Arankalle, Vidya A

    2014-10-01

    Retrospective serologic screening of 1077 serum samples collected from the primitive tribe from north-eastern India in 1963 revealed high prevalence of HBV (15% HBsAg carrier rate) and HCV (7% anti-HCV positivity) and co-circulation of multiple HBV genotypes-A, C, D and G. Full genome sequencing classified all the G-genotype samples as genotype-I. Comparison of genotype-I-HBV full-genome sequences representing 1963 (n=5, this study) and 2005 (reported earlier) showed identical recombination break-points of genotypes-A/G/C. Genotype-C and genotype-C-fragment of I-genotype circulating in 1963 were distinctly different. The data demonstrates that the recombination events were not recent. Molecular clock analysis predicted existence of genotype-I in this tribe during 1920s.

  18. Discharge Asymmetry in Delta Bifurcations

    NASA Astrophysics Data System (ADS)

    Salter, G.; Paola, C.; Voller, V. R.

    2015-12-01

    Distributary networks are formed by channels which bifurcate downstream in a river delta. Sediment and water fluxes are often split unequally in delta bifurcations. Understanding flux asymmetry in distributary networks is important for predicting how a delta will respond to sea-level rise. We present results of a quasi-1D model of a delta bifurcation. Consistent with previous results, in the absence of deposition, stable bifurcations may be either symmetric or asymmetric, depending on flow conditions. However, in a depositional setting, a stable asymmetric flow partitioning is no longer possible, as the dominant branch becomes less and less steep relative to the other branch. This feedback eventually causes the second branch to become favored. For the depositional case, we identify three regimes of bifurcation behavior: 1) stable symmetric bifurcation, 2) "soft" avulsions where the dominant branch switches without complete abandonment of the previous channel, and 3) complete avulsions where one branch is completely abandoned. In each case, the bifurcation is symmetric in the long-term average, but the latter two allow for short-term asymmetry. We find that keeping upstream sediment and water discharges fixed, as downstream channel length increases the regime shifts from symmetric to soft avulsions to complete avulsions. In the two avulsion regimes we examine the effect of upstream sediment and water discharges and downstream channel length on avulsion period and maximum discharge ratio. Finally, we compare numerical modeling results to a fixed-wall bifurcation experiment. As in the numerical model, the presence or absence of a downstream sink exerts a strong control on system behavior. If a sink is present, a bifurcation may be asymmetric indefinitely. Conversely, without a sink the system is depositional, and the feedback between sediment discharge asymmetry and slope causes the bifurcation to remain symmetric in the long-term average.

  19. Novel Immunotherapies for Autoimmune Hepatitis

    PubMed Central

    Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal

    2017-01-01

    Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4+ T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects. PMID:28184367

  20. Novel Immunotherapies for Autoimmune Hepatitis.

    PubMed

    Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal

    2017-01-01

    Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4(+) T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects.

  1. Delta-Doped Back-Illuminated CMOS Imaging Arrays: Progress and Prospects

    NASA Technical Reports Server (NTRS)

    Hoenk, Michael E.; Jones, Todd J.; Dickie, Matthew R.; Greer, Frank; Cunningham, Thomas J.; Blazejewski, Edward; Nikzad, Shouleh

    2009-01-01

    In this paper, we report the latest results on our development of delta-doped, thinned, back-illuminated CMOS imaging arrays. As with charge-coupled devices, thinning and back-illumination are essential to the development of high performance CMOS imaging arrays. Problems with back surface passivation have emerged as critical to the prospects for incorporating CMOS imaging arrays into high performance scientific instruments, just as they did for CCDs over twenty years ago. In the early 1990's, JPL developed delta-doped CCDs, in which low temperature molecular beam epitaxy was used to form an ideal passivation layer on the silicon back surface. Comprising only a few nanometers of highly-doped epitaxial silicon, delta-doping achieves the stability and uniformity that are essential for high performance imaging and spectroscopy. Delta-doped CCDs were shown to have high, stable, and uniform quantum efficiency across the entire spectral range from the extreme ultraviolet through the near infrared. JPL has recently bump-bonded thinned, delta-doped CMOS imaging arrays to a CMOS readout, and demonstrated imaging. Delta-doped CMOS devices exhibit the high quantum efficiency that has become the standard for scientific-grade CCDs. Together with new circuit designs for low-noise readout currently under development, delta-doping expands the potential scientific applications of CMOS imaging arrays, and brings within reach important new capabilities, such as fast, high-sensitivity imaging with parallel readout and real-time signal processing. It remains to demonstrate manufacturability of delta-doped CMOS imaging arrays. To that end, JPL has acquired a new silicon MBE and ancillary equipment for delta-doping wafers up to 200mm in diameter, and is now developing processes for high-throughput, high yield delta-doping of fully-processed wafers with CCD and CMOS imaging devices.

  2. Comparative Molecular Dynamics Simulation of Hepatitis C Virus NS3/4A Protease (Genotypes 1b, 3a and 4a) Predicts Conformational Instability of the Catalytic Triad in Drug Resistant Strains

    PubMed Central

    Kramer, Mitchell; Halleran, Daniel; Rahman, Moazur; Iqbal, Mazhar; Anwar, Muhammad Ikram; Sabet, Salwa; Ackad, Edward; Yousef, Mohammad

    2014-01-01

    The protease domain of the Hepatitis C Virus (HCV) nonstructural protein 3 (NS3) has been targeted for inhibition by several direct-acting antiviral drugs. This approach has had marked success to treat infections caused by HCV genotype 1 predominant in the USA, Europe, and Japan. However, genotypes 3 and 4, dominant in developing countries, are resistant to a number of these drugs and little progress has been made towards understanding the structural basis of their drug resistivity. We have previously developed a 4D computational methodology, based on 3D structure modeling and molecular dynamics simulation, to analyze the active sites of the NS3 proteases of HCV-1b and 4a in relation to their catalytic activity and drug susceptibility. Here, we improved the methodology, extended the analysis to include genotype 3a (predominant in South Asia including Pakistan), and compared the results of the three genotypes (1b, 3a and 4a). The 4D analyses of the interactions between the catalytic triad residues (His57, Asp81, and Ser139) indicate conformational instability of the catalytic site in HCV-3a and 4a compared to that of HCV-1b NS3 protease. The divergence is gradual and genotype-dependent, with HCV-1b being the most stable, HCV-4a being the most unstable and HCV-3a representing an intermediate state. These results suggest that the structural dynamics behavior, more than the rigid structure, could be related to the altered catalytic activity and drug susceptibility seen in NS3 proteases of HCV-3a and 4a. PMID:25111232

  3. Hepatic hematoma and hepatic rupture in pregnancy.

    PubMed

    Poo, Jorge Luis; Góngora, Julieta

    2006-01-01

    Hepatic perforation is an unusual complication of woman pregnancy associated with a poor outcome. A comprehensive review of epidemiology, clinical spectrum, diagnostic methods and therapeutic options is presented in this short paper.

  4. Glucagon receptor of human liver. Studies of its molecular weight and binding properties, and its ability to activate hepatic adenylyl cyclase of non-obese and obese subjects.

    PubMed Central

    Livingston, J N; Einarsson, K; Backman, L; Ewerth, S; Arner, P

    1985-01-01

    The glucagon receptor and the adenylyl cyclase system of human liver membranes were studied in six non-obese and six obese subjects who had elevated insulin and plasma glucagon levels. Analysis of specific glucagon binding by the method of Scatchard demonstrated a linear (monocomponent) plot with a dissociation constant of 2-3 nM, and the binding at low hormone concentrations was sensitive to guanosine triphosphate (GTP). The molecular weight of the glucagon receptor was 63,000 D as determined by an affinity labeling procedure and sodium dodecyl sulfate gel electrophoresis. Affinity labeling of this structure was specific for glucagon and inhibited by GTP. Glucagon stimulated the production of cyclic adenosine monophosphate (cAMP) by human membranes with half-maximal activation elicited by 6 nM hormone. The human cyclase system required GTP to facilitate an optimal glucagon response. NaF (10 mM) also activated the cyclase system and produced the same magnitude of response as maximum glucagon activation. A comparison of the liver adenylyl cyclase system of non-obese and obese subjects was made using glucagon (5 nM and 1 microM) and NaF (10 mM). No significant differences in cAMP production were noted between the two groups, regardless of the agent used to activate the enzyme. These findings agree with the glucagon binding studies that showed similar amounts of binding activity in the membranes from the two groups. Also, there was no influence of either age or sex of the subjects on the adenylyl cyclase response. In conclusion, human liver membranes contain a glucagon receptor and an adenylyl cyclase system that correspond closely to the well-studied system in animal liver. This system in human obesity is not altered by the approximately twofold elevation in plasma glucagon that occurs in this metabolic disorder. Images PMID:2982913

  5. Deformation characteristics of {delta} phase in the delta-processed Inconel 718 alloy

    SciTech Connect

    Zhang, H.Y.; Zhang, S.H.; Cheng, M.; Li, Z.X.

    2010-01-15

    The hot working characteristics of {delta} phase in the delta-processed Inconel 718 alloy during isothermal compression deformation at temperature of 950 deg. C and strain rate of 0.005 s{sup -1}, were studied by using optical microscope, scanning electron microscope and quantitative X-ray diffraction technique. The results showed that the dissolution of plate-like {delta} phase and the precipitation of spherical {delta} phase particles coexisted during the deformation, and the content of {delta} phase decreased from 7.05 wt.% to 5.14 wt.%. As a result of deformation breakage and dissolution breakage, the plate-like {delta} phase was spheroidized and transferred to spherical {delta} phase particles. In the center with largest strain, the plate-like {delta} phase disappeared and spherical {delta} phase appeared in the interior of grains and grain boundaries.

  6. Autophagy in hepatic fibrosis.

    PubMed

    Song, Yang; Zhao, Yingying; Wang, Fei; Tao, Lichan; Xiao, Junjie; Yang, Changqing

    2014-01-01

    Hepatic fibrosis is a leading cause of morbidity and mortality worldwide. Hepatic fibrosis is usually associated with chronic liver diseases caused by infection, drugs, metabolic disorders, or autoimmune imbalances. Effective clinical therapies are still lacking. Autophagy is a cellular process that degrades damaged organelles or protein aggregation, which participates in many pathological processes including liver diseases. Autophagy participates in hepatic fibrosis by activating hepatic stellate cells and may participate as well through influencing other fibrogenic cells. Besides that, autophagy can induce some liver diseases to develop while it may play a protective role in hepatocellular abnormal aggregates related liver diseases and reduces fibrosis. With a better understanding of the potential effects of autophagy on hepatic fibrosis, targeting autophagy might be a novel therapeutic strategy for hepatic fibrosis in the near future.

  7. Preventing hepatitis B or C

    MedlinePlus

    ... 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 ...

  8. Delta deposition influenced by diapiric uplifts

    SciTech Connect

    Kindinger, J.L.

    1988-01-01

    The continental shelf in the northern Gulf of Mexico is overlain by many superimposed deltas. One late Wisconsinan delta, here informally named the lagniappe, is located east of the Mississippi River bird-foot delta and extends from mid-shelf to the continental slope. The lagniappe delta is adjacent to, but not genetically associated with, the Mississippi River delta complex. The lagniappe delta is a shelf-margin delta formed in part by stream erosion of the exposed inner and outer shelf during the late Wisconsinan lowstand. On the basis of its overall pattern and direction of accretion, the delta's fluvial source was most probably the ancient Pearl or Mobile River farther east. The progradational deposits, as seen in the high-resolution seismic reflection profile, are characterized by foreset and bottomset bedding. Areal distribution and sediment thickness were partially controlled by two diapirs active before and during deltaic sedimentation. The diapirs were a barrier to seaward progradation. As the delta prograded seaward, sediment ponded in an area between and shoreward of both uplifted diapirs. The basic geometry of the lagniappe delta was effectively changed during deposition by the presence of these diapirs.

  9. Future Deltas Utrecht University research focus area: towards sustainable management of sinking deltas

    NASA Astrophysics Data System (ADS)

    Stouthamer, E.; van Asselen, S.

    2015-11-01

    Deltas are increasingly under pressure from human impact and climate change. To deal with these pressures that threat future delta functioning, we need to understand interactions between physical, biological, chemical and social processes in deltas. This requires an integrated approach, in which knowledge on natural system functioning is combined with knowledge on spatial planning, land and water governance and legislative frameworks. In the research focus area Future Deltas of Utrecht University an interdisciplinary team from different research groups therefore works together. This allows developing integrated sustainable and resilient delta management strategies, which is urgently needed to prevent loss of vital delta services.

  10. [From the national competence network for viral hepatitis (HepNet) emerged the German Liver Foundation (Deutsche Leberstiftung)].

    PubMed

    Hardtke, S; Wiebner, B; Manns, M P

    2016-04-01

    The competence network for viral hepatitis (HepNet) was founded in 2002 with funding from the German government and has influenced the research on viral hepatitis in Germany. HepNet collaborator sites have been involved in numerous national and international investigator-initiated, as well as industry-sponsored, phase 1-3 studies. Within the HepNet Study-House, many groundbreaking investor-initiated trials have been completed and are still ongoing. For example, the acute hepatitis C trials and trials on chronic hepatitis D (delta), which led to therapy optimization. Continuation of the competence network on viral hepatitis has been achieved by the foundation of the German Liver Foundation, which has been an external cooperation partner of the German Center for Infection Research (DZIF) for two years. The well-established HepNet Study-House acts here as the clinical trial platform for all DZIF hepatitis trials.

  11. Ostrich crystallins. Structural characterization of delta-crystallin with enzymic activity.

    PubMed Central

    Chiou, S H; Lo, C H; Chang, C Y; Itoh, T; Kaji, H; Samejima, T

    1991-01-01

    Lens crystallins from the African ostrich (Struthio camelus) were isolated and characterized. Four crystallin fractions corresponding to alpha-, delta/beta- and beta-crystallins similar to those of duck crystallins were isolated, but epsilon-crystallin was found to be absent. The native molecular masses and subunit structures of the purified fractions were analysed by gel filtration. SDS/PAGE and isoelectric focusing, revealing various extents of heterogeneity in each orthologous crystallin class. An ion-exchange chromatographic method was used for the large-scale preparation of delta-crystallin suitable for structural and enzymic studies. It was unexpectedly found that the purified native delta-crystallin of ostrich lens possessed high argininosuccinate lyase activity, in contrast with chicken delta-crystallin. The c.d. spectra indicated a predominant beta-sheet structure in alpha- and beta-crystallins, and a significant contribution of alpha-helical structure in the delta-crystallin fraction. The estimate of secondary structures from c.d. spectroscopy for each crystallin class bears a resemblance to that of duck crystallins, except that ostrich delta-crystallin possesses much less helical content than duck delta-crystallin. Comparison of crystallin compositions and structures from aquatic and terrestrial birds revealed distinct differences. Images Fig. 1. Fig. 2. Fig. 3. PMID:1991029

  12. Hepatitis B virus burden in developing countries.

    PubMed

    Zampino, Rosa; Boemio, Adriana; Sagnelli, Caterina; Alessio, Loredana; Adinolfi, Luigi Elio; Sagnelli, Evangelista; Coppola, Nicola

    2015-11-14

    Hepatitis B virus (HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence of hepatitis B surface antigen chronic carriers have decreased in several countries because of the HBV universal vaccination programs started in the nineties. Some countries, however, are still unable to implement these programs, particularly in their hyperendemic rural areas. The diffusion of HBV infection is still wide in several low-income countries where the prevention, management and treatment of HBV infection are a heavy burden for the governments and healthcare authorities. Of note, the information on the HBV epidemiology is scanty in numerous eastern European and Latin-American countries. The studies on molecular epidemiology performed in some countries provide an important contribution for a more comprehensive knowledge of HBV epidemiology, and phylogenetic studies provide information on the impact of recent and older migratory flows.

  13. COMMD1 regulates the delta epithelial sodium channel ({delta}ENaC) through trafficking and ubiquitination

    SciTech Connect

    Chang, Tina; Ke, Ying; Ly, Kevin; McDonald, Fiona J.

    2011-08-05

    Highlights: {yields} The COMM domain of COMMD1 mediates binding to {delta}ENaC. {yields} COMMD1 reduces the cell surface population of {delta}ENaC. {yields} COMMD1 increases the population of {delta}ENaC-ubiquitin. {yields} Both endogenous and transfected {delta}ENaC localize with COMMD1 and transferrin suggesting they are located in early/recycling endosomes. -- Abstract: The delta subunit of the epithelial sodium channel ({delta}ENaC) is a member of the ENaC/degenerin family of ion channels. {delta}ENaC is distinct from the related {alpha}-, {beta}- and {gamma}ENaC subunits, known for their role in sodium homeostasis and blood pressure control, as {delta}ENaC is expressed in brain neurons and activated by external protons. COMMD1 (copper metabolism Murr1 domain 1) was previously found to associate with and downregulate {delta}ENaC activity. Here, we show that COMMD1 interacts with {delta}ENaC through its COMM domain. Co-expression of {delta}ENaC with COMMD1 significantly reduced {delta}ENaC surface expression, and led to an increase in {delta}ENaC ubiquitination. Immunocytochemical and confocal microscopy studies show that COMMD1 promoted localization of {delta}ENaC to the early/recycling endosomal pool where the two proteins were localized together. These results suggest that COMMD1 downregulates {delta}ENaC activity by reducing {delta}ENaC surface expression through promoting internalization of surface {delta}ENaC to an intracellular recycling pool, possibly via enhanced ubiquitination.

  14. Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype

    PubMed Central

    Madejón, Antonio; Romero, Míriam; Hernández, Ángela; García-Sánchez, Araceli; Sánchez-Carrillo, Marta; Olveira, Antonio; García-Samaniego, Javier

    2016-01-01

    AIM: To study the hepatitis B virus (HBV) and hepatitis D virus (HDV) replication interferences in patients with chronic hepatitis delta infected with different HBV genotypes. METHODS: We conducted a transversal study including 68 chronic hepatitis delta (CHD) (37 HIV-positive) patients and a control group of 49 chronic hepatitis B (CHB) (22 HIV-positive) patients. In addition, a dynamic follow-up was performed in 16 CHD patients. In all the samples, the surface antigen of hepatitis B (HBsAg) serum titers were analyzed with the Monolisa HBsAg Ultra system (Bio-Rad), using as quantification standard a serial dilution curve of an international HBsAg standard. Serum HBV-DNA titers were analyzed using the Roche Cobas TaqMan (Roche, Barcelona, Spain), and the serum HDV-RNA using an in-house real-time qRT-PCR method, with TaqMan probes. HBV genotype was determined with the line immunoassay LiPA HBV genotyping system (Innogenetics, Ghent, Belgium). In those patients negative for LiPA assay, a nested PCR method of complete HBsAg coding region, followed by sequence analysis was applied. RESULTS: No differences in the HBV-DNA levels were found in CHB patients infected with different HBV genotypes. However, in CHD patients the HBV-DNA levels were lower in those infected with HBV-A than in those with HBV-D, both in HIV negative [median (IQR): 1.25 (1.00-1.35) vs 2.95 (2.07-3.93) log10 (copies/mL), P = 0.013] and HIV positive patients [2.63 (1.24-2.69) vs 7.25 (4.61-7.55) log10 (copies/mL), P < 0.001]. This was confirmed in the dynamic study of the HBV/HDV patients. These differences induce an under-estimation of HBV-A incidence in patients with CHD analyzed with LiPA assay. Finally, the HBsAg titers reflected no significant differences in CHD patients infected with HBV-A or D. CONCLUSION: Viral replication interference between HBV and HDV is HBV-genotype dependent, and more evident in patients infected with HBV-genotype A, than with HBV-D or E. PMID:27003993

  15. Mission Stream Analysis - Delta Analytic Model. Revision

    DTIC Science & Technology

    2014-09-01

    demonstrating mission effectiveness. The second tool is the  ( Delta ) Analytic Model, which provides an approach for identifying disparate...requirements into a system’s technical performance and operator workload requirements; and help minimize the “ delta ” between domains across the system’s...mission and system capability requirements into a system’s technical performance and operator workload requirements; and help minimize the “ delta

  16. Delta Clipper vehicle design for supportability

    NASA Astrophysics Data System (ADS)

    Smiljanic, Ray R.; Klevatt, Paul L.; Steinmeyer, Donald A.

    1993-02-01

    The paper describes the Single Stage Rocket Technology (SSRT) Delta Clipper vehicle design. As a means of reducing vehicle processing and turnaround times, the SSRT Delta Clipper design, contrary to past practices, incorporates support ability engineering features into its initial set of design requirements. The engineering process used to 'design-in' supportability into the Delta Clipper vehicle is described in detail and is illustrated using diagrams.

  17. Delta Clipper - Design for supportability

    NASA Astrophysics Data System (ADS)

    Smiljanic, Ray R.; Conrad, Charles; Spaulding, Ed; Gisburne, Don

    1993-07-01

    The 'Delta Clipper' Single Stage Rocket Technology (SSRT) currently under development in the DC-X program will implement reliability-centered maintenance and support, involving on-equipment/off-equipment two-level maintenance, a logistics and spares pipeline, and a minimization of 'blue suit' skill-level personnel. Attention is given to the range of SSRT features that are to be validated via the DC-X test program; these prominently involve LRUs replaceability and accessibility, standardization and interchangeability, and 'aircraft-like' automated data collection.

  18. Climate change and the Delta

    USGS Publications Warehouse

    Dettinger, Michael; Anderson, Jamie; Anderson, Michael L.; Brown, Larry R.; Cayan, Daniel; Maurer, Edwin P.

    2016-01-01

    Anthropogenic climate change amounts to a rapidly approaching, “new” stressor in the Sacramento–San Joaquin Delta system. In response to California’s extreme natural hydroclimatic variability, complex water-management systems have been developed, even as the Delta’s natural ecosystems have been largely devastated. Climate change is projected to challenge these management and ecological systems in different ways that are characterized by different levels of uncertainty. For example, there is high certainty that climate will warm by about 2°C more (than late-20th-century averages) by mid-century and about 4°C by end of century, if greenhouse-gas emissions continue their current rates of acceleration. Future precipitation changes are much less certain, with as many climate models projecting wetter conditions as drier. However, the same projections agree that precipitation will be more intense when storms do arrive, even as more dry days will separate storms. Warmer temperatures will likely enhance evaporative demands and raise water temperatures. Consequently, climate change is projected to yield both more extreme flood risks and greater drought risks. Sea level rise (SLR) during the 20th century was about 22cm, and is projected to increase by at least 3-fold this century. SLR together with land subsidence threatens the Delta with greater vulnerabilities to inundation and salinity intrusion. Effects on the Delta ecosystem that are traceable to warming include SLR, reduced snowpack, earlier snowmelt and larger storm-driven streamflows, warmer and longer summers, warmer summer water temperatures, and water-quality changes. These changes and their uncertainties will challenge the operations of water projects and uses throughout the Delta’s watershed and delivery areas. Although the effects of climate change on Delta ecosystems may be profound, the end results are difficult to predict, except that native species will fare worse than invaders. Successful

  19. Chemical mechanism of the endogenous argininosuccinate lyase activity of duck lens delta2-crystallin.

    PubMed Central

    Wu, C Y; Lee, H J; Wu, S H; Chen, S T; Chiou, S H; Chang, G G

    1998-01-01

    The endogenous argininosuccinate lyase activity of duck delta2-crystallin was specifically inactivated by the histidine-specific reagent, diethyl pyrocarbonate. The protein was protected by l-citrulline or l-arginine from the diethyl pyrocarbonate inactivation. To characterize further the chemical mechanism of the delta2-crystallin-catalysed reaction, deuterium-labelled argininosuccinate was enzymically synthesized from fumarate and l-arginine with delta2-crystallin in 2H2O. The argininosuccinate synthesized contained about 19% of the anhydride form; however, the deuterium was clearly demonstrated to be incorporated enantioselectively. Only the pro-HR atom at C-9 of the succinate moiety was labelled in the [2H]argininosuccinate-9-d synthesized, which indicates an anti-elimination mechanism for the endogenous argininosuccinate lyase activity of delta2-crystallin. The enzymic activity of duck lens delta2-crystallin in the pH range 5.5-8.5 was investigated using both protium- and deuterium-labelled argininosuccinate as the substrate. From the logkcat versus pH plot, two molecular pKa values of 6.18+/-0.02 and 8.75+/-0.03 were detected in the delta2-crystallin-argininosuccinate binary complex. The former must be dehydronated and the latter hydronated to achieve an optimum reaction rate. The logkcat/Km versus pH plot suggested two molecular pKa values of 5.96+/-0.09 and 8.29+/-0.10 for the free delta2-crystallin to be involved in the substrate binding. Small kinetic isotope effects of 1.17+/-0.02 and 1.05+/-0.09 were found for kcat and kcat/Km respectively. Combining results from labelling and kinetic analysis indicates that the endogenous argininosuccinate lyase activity of duck delta2-crystallin is compatible with a stepwise E1cB mechanism, the rate-limiting step probably at the C-N bond-cleavage step. PMID:9657972

  20. Navigational Use of Cassini Delta V Telemetry

    NASA Technical Reports Server (NTRS)

    Roth, Duane C.; Antreasian, Peter G.; Ardalan, Shadan M.; Criddle, Kevin E.; Goodson, Troy; Ionasescu, Rodica; Jones, Jeremy B.; Parcher, Daniel W.; Pelletier, Frederic J.; Thompson, Paul F.; Vaughan, Andrew T.

    2008-01-01

    Telemetry data are used to improve navigation of the Saturn orbiting Cassini spacecraft. Thrust induced delta V's are computed on-board the spacecraft, recorded in telemetry, and downlinked to Earth. This paper discusses how and why the Cassini Navigation team utilizes spacecraft delta V telemetry. Operational changes making this information attractive to the Navigation Team will be briefly discussed, as will spacecraft hardware and software algorithms responsible for the on-board computation. An analysis of past delta V telemetry, providing calibrations and accuracies that can be applied to the estimation of future delta V activity, is described.

  1. From Natural to Design River Deltas

    NASA Astrophysics Data System (ADS)

    Giosan, Liviu

    2016-04-01

    Productive and biologically diverse, deltaic lowlands attracted humans since prehistory and may have spurred the emergence of the first urban civilizations. Deltas continued to be an important nexus for economic development across the world and are currently home for over half a billion people. But recently, under the double whammy of sea level rise and inland sediment capture behind dams, they have become the most threatened coastal landscape. Here I will address several deceptively simple questions to sketch some unexpected answers using example deltas from across the world from the Arctic to the Tropics, from the Danube to the Indus, Mississippi to Godavari and Krishna, Mackenzie to Yukon. What is a river delta? What is natural and what is not in a river delta? Are the geological and human histories of a delta important for its current management? Is maintaining a delta the same to building a new one? Can we design better deltas than Nature? These answers help us see clearly that survival of deltas in the next century depends on human intervention and is neither assured nor simple to address or universally applicable. Empirical observations on the hydrology, geology, biology and biochemistry of deltas are significantly lagging behind modeling capabilities endangering the applicability of numerical-based reconstruction solutions and need to be ramped up significantly and rapidly across the world.

  2. {Delta} isobars and (p,p') reactions

    SciTech Connect

    Sammarruca, F.; Stephenson, E. J.

    2001-09-01

    We explore the role of coupling to {Delta} isobars (in both the N{Delta} and {Delta}{Delta} channels) in medium modifications of the effective NN interaction that drives 200-MeV proton inelastic scattering. A comparison of the predictions to natural-parity (p,p') cross section and analyzing power data show that isobar degrees of freedom in the medium generate overly repulsive effective interactions. Furthermore, this model extension is unable to resolve difficulties observed earlier describing polarization transfer measurements in some high-spin, unnatural-parity (p,p') transitions.

  3. Comments on the slip factor and the relation Delta phi = -h Delta theta

    SciTech Connect

    Ng, K.Y.; /Fermilab

    2009-09-01

    The definition of the slip factor can be obtained from the phase equation. However, a derivation using the relation {Delta}{phi} = -h{Delta}{theta} leads to a different slip-factor definition. This apparent paradox is examined in detail and resolved. Here {Delta}{phi} is the rf phase difference and {Delta}{theta} is the azimuthal phase difference around the accelerator ring between an off-momentum particle and the synchronous particle, while h is the rf harmonic.

  4. Developing a Truly Global Delta Database to Assess Delta Morphology and Morphodynamics

    NASA Astrophysics Data System (ADS)

    Caldwell, R. L.; Edmonds, D. A.; Baumgardner, S. E.; Whaling, A.

    2015-12-01

    Delta morphology reflects the interplay of various environmental parameters, though these relationships have only been tested on small datasets with 30-50 deltas. These datasets are biased toward the largest deltas, which typically have compound morphologies, form on passive margins, and may not be representative of the full breadth in delta morphology. With the goal of building more robust predictions of delta morphology to enhance hazard mitigation and resiliency planning, we have developed a truly global delta database including every delta on the world's marine coastlines. Using Google Earth imagery, we first identified all fluvial river mouths (≥ 50 m wide) connected to an upstream catchment. Deltas are defined geomorphically as river mouths that split into two or more active or relict distributary channels, end in a depositional protrusion from the shoreline, or do both. In our database we identified 5,801 river mouths, and 1,426 of those coastal rivers (~25%) have a geomorphic delta. ~75% of deltas exhibit an active or relict distributary network, while the remaining ~25% are single channel deltas with a basinward protrusion. Preliminary morphometric analysis (ratio of shore-parallel width, W, to shore-perpendicular length, L) on a subset of 159 deltas suggests W:L values range from 0.52 (elongate) to 23.6 (broad/cuspate). The median W:L value is 2.68, suggesting the majority of deltas are roughly semi-circular (W:L = 2), and the distribution is heavily skewed to the broad/cuspate deltas (~28% are >4 times wider than they are long). Preliminary comparison to downstream significant wave height data shows that the 'wider' deltas relate to higher wave heights (R2 = 0.42), though the data are scattered. Ultimately, the database will include additional measured morphometrics, including number of channel mouths and delta area, and morphodynamic data derived from serial Landsat imagery.

  5. The Atchafalaya River Delta. Report 1. A Plan for Predicting Delta Evolution

    DTIC Science & Technology

    1991-05-01

    Report HL-85-1, US Army Engineer Waterways Experi- ment Station, Vicksburg, MS. Thomas, W. A., Heath, R. E., Stewart, J. P., and Clark , D G., 1988...the Brazilian Continental Margin, Belem City. Para, Brazil, 29 October- 4 November 1972. pp 145-155. WAVES, DISCHARGE, DELTAS. Coleman, J. M., and...and Clark , D. G. 1988 (Dec). "The Atchafalaya River Delta Report 5, The Atchafalaya River Delta Quasi-Two- Dimensional Model of Delta Growth and

  6. Hepatitis C -- children

    MedlinePlus

    ... children; HCV children; Pregnancy - hepatitis C - children; Maternal transmission - hepatitis C - children References Elisofon SA, Jonas MMF. ... Hospital, Hollywood, FL. Review provided by VeriMed Healthcare Network. Also reviewed by David ... this important distinction for online health information and services. Learn more about A.D.A. ...

  7. Heavy Metals in Liver and Brain of Waterfowl from the Evros Delta, Greece.

    PubMed

    Aloupi, Maria; Karagianni, Asimina; Kazantzidis, Savas; Akriotis, Triantaphyllos

    2017-02-01

    The concentrations of six heavy metals (cadmium [Cd], chromium [Cr], copper [Cu], manganese [Mn], lead [Pb], and zinc [Zn]) were determined in liver and brain of nine species of waterfowl from the Evros Delta, one of the most important wetlands in Greece, to assess metal contamination and potential risk to waterfowl. Significant differences among species were found for hepatic Cr, Cu, Pb, and Zn; the highest levels of all metals were found in liver of mute swans. Cd increased significantly with age in both organs of wigeon; some differences were also observed between males and females of the same species. Feeding habits were found to significantly affect hepatic Cr, Zn, and Cu concentrations with greater concentrations found in herbivorous than omnivorous species. Several significant positive correlations between metals were detected mainly in liver samples, which were attributable either to their association to metallothioneins or to common routes of exposure of waterfowl. Hepatic and cerebral concentrations of Cd and Pb correlated positively. Given the discrepancies in the thresholds or critical levels of metals in tissues of waterfowl, our survey showed that environmental exposure to increased levels of heavy metals may threaten, at least to some degree, the populations of waterfowl wintering in the Evros Delta. In a small percentage of birds, values indicative of severe adverse effects were determined. Swans that had been found dead showed some of the highest values, whereas accumulation levels did not follow a consistent pattern among the ducks examined.

  8. Update on Alcoholic Hepatitis.

    PubMed

    Torok, Natalie J

    2015-11-02

    Alcoholic liver disease is one of the most prevalent liver diseases worldwide, and a major cause of morbidity and mortality. Alcoholic hepatitis is a severe form of liver injury in patients with alcohol abuse, can present as an acute on chronic liver failure associated with a rapid decline in liver synthetic function, and consequent increase in mortality. Despite therapy, about 30%-50% of patients with severe alcoholic hepatitis eventually die. The pathogenic pathways that lead to the development of alcoholic hepatitis are complex and involve oxidative stress, gut dysbiosis, and dysregulation of the innate and adaptive immune system with injury to the parenchymal cells and activation of hepatic stellate cells. As accepted treatment approaches are currently limited, a better understanding of the pathophysiology would be required to generate new approaches that improve outcomes. This review focuses on recent advances in the diagnosis, pathogenesis of alcoholic hepatitis and novel treatment strategies.

  9. Viral Hepatitis: Information for Gay and Bisexual Men

    MedlinePlus

    VIRAL HEPATITIS Information for Gay and Bisexual Men What is viral hepatitis? Viral hepatitis is an infection of the liver caused by ... United States, the most common types of viral hepatitis are Hepatitis A, Hepatitis B, and Hepatitis C. ...

  10. CASSCF/CI calculations for first row transition metal hydrides - The TiH(4-phi), VH(5-delta), CrH(6-sigma-plus), MnH(7-sigma-plus), FeH(4,6-delta) and NiH(2-delta) states

    NASA Technical Reports Server (NTRS)

    Walch, S. P.; Bauschlicher, C. W., Jr.

    1983-01-01

    Calculations are performed for the predicted ground states of TiH(4-phi), VH(5-delta), CrH(6-sigma-plus), MnH(7-sigma-plus), Fett(4,6-delta) and NiH(2-delta). For FeH both the 6-delta and 4-delta states are studied, since both are likely candidates for the ground state. The ground state symmetries are predicted based on a combination of atomic coupling arguments and coupling of 4s(2)3d(n) and 4s(1)3d(n+1) terms in the molecular system. Electron correlation is included by a CASSCF/CI (SD) treatment. The CASSCF includes near-degeneracy effects, while correlation of the 3d electrons in included at the CI level.

  11. Posterior reversible encephalopathy syndrome in alcoholic hepatitis: Hepatic encephalopathy a common theme.

    PubMed

    John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita

    2017-01-14

    Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome.

  12. Posterior reversible encephalopathy syndrome in alcoholic hepatitis: Hepatic encephalopathy a common theme

    PubMed Central

    John, Elizabeth S; Sedhom, Ramy; Dalal, Ishita; Sharma, Ranita

    2017-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a neuro-radiologic diagnosis that has become more widely recognized and reported over the past few decades. As such, there are a number of known risk factors that contribute to the development of this syndrome, including volatile blood pressures, renal failure, cytotoxic drugs, autoimmune disorders, pre-eclampsia, and eclampsia. This report documents the first reported case of PRES in a patient with severe alcoholic hepatitis with hepatic encephalopathy and delves into a molecular pathophysiology of the syndrome. PMID:28127211

  13. Molecular orchestration of the hepatic circadian symphony.

    PubMed

    Albrecht, Urs

    2006-01-01

    The circadian clock determines the rhythmic expression of many different genes throughout a 24-hour period. A recent study investigating the circadian regulation of liver proteins reveals multiple levels of regulation, including transcriptional, post-transcriptional and post-translational mechanisms.

  14. Biomagnification profiles of polycyclic aromatic hydrocarbons, alkylphenols and polychlorinated biphenyls in Tokyo Bay elucidated by delta13C and delta15N isotope ratios as guides to trophic web structure.

    PubMed

    Takeuchi, Ichiro; Miyoshi, Noriko; Mizukawa, Kaoruko; Takada, Hideshige; Ikemoto, Tokutaka; Omori, Koji; Tsuchiya, Kotaro

    2009-05-01

    Biomagnification profiles of polycyclic aromatic hydrocarbons (PAHs), alkylphenols, and polychlorinated biphenyls (PCBs) from the innermost part of Tokyo Bay, Japan were analyzed using stable carbon (delta(13)C) and nitrogen (delta(15)N) isotope ratios as guides to trophic web structure. delta(15)N analysis indicated that all species of mollusks tested were primary consumers, while decapods and fish were secondary consumers. Higher concentrations of PCBs occurred in decapods and fish than in mollusks. In contrast, concentrations of PAHs and alkylphenols were lower in decapods and fish than in mollusks. Unlike PCBs, whose concentrations largely increased with increasing delta(15)N (i.e. increasing trophic level), all PAHs and alkylphenols analyzed followed a reverse trend. Molecular weights of PAHs are lower than those of PCBs, therefore low membrane permeability caused by large molecular size is an unlikely factor in the "biodilution" of PAHs. Organisms at higher trophic levels may rapidly metabolize PAHs or they may assimilate less of them.

  15. [The ABC of viral hepatitis].

    PubMed

    Van Bambeke, F

    2008-03-01

    Viral hepatitis has long been under-diagnosed. Hepatitis A is an acute disease, while patients infected by hepatitis B and hepatitis C viruses are likely to develop chronical infections and severe complications (cancer, cirrhosis). The current treatment of hepatitis B and C consists in alpha interferon (preferably under its pegylated form), in combination with ribavirin for hepatitis C. The frequent and severe adverse effects of interferon-based therapy constitute, however, a major limiting factor (reactions at the injection site, flu-like syndrome, neurological disorders, ...). For hepatitis B, two alternatives are available so far, namely lamivudine and adefovir (used as a prodrug with highe oral bioavailability).

  16. Revision of the Delta Nursing Scales.

    ERIC Educational Resources Information Center

    Wilson, Barry J.; Packwood, Gene

    An item analysis was performed on two rating scales, the Delta Survey of Nurses and the Delta Nursing Survey, developed for evaluating the preparation and job performance of nursing graduates. Resulting data supported the basic design of the instruments. The revised instruments consist of seven fewer items; two subtests were deleted, and a number…

  17. Electromagnetic excitation of the Delta(1232) resonance

    SciTech Connect

    V. Pascalutsa; M. Vanderhaeghen; Shin Nan Yang

    2006-09-05

    We review the description of the lowest-energy nucleon excitation--the Delta(1232)-resonance. Much of the recent effort has been focused on the precision measurements of the nucleon to Delta transition by means of electromagnetic probes. We review the results of those measurements and confront them with the state-of-the-art calculations based on chiral effective-field theories (EFT), lattice QCD, and QCD-inspired models. Some of the theoretical approaches are reviewed in detail. In particular, we describe the chiral EFT of QCD in the energy domain of the Delta-resonance, and its applications to the electromagnetic nucleon-to-Delta transition (gamma N Delta). We also describe the recent dynamical and unitary-isobar models of pion electroproduction which are extensively used in the extraction of the gamma* N Delta form factors from experiment. Furthermore, we discuss the link of the gamma* N Delta form factors to generalized parton distributions (GPDs), as well as the predictions of perturbative QCD for these transition form factors. The present status of understanding the Delta-resonance properties and the nature of its excitation is summarized.

  18. Delta Blues Scholarship and Imperialist Nostalgia.

    ERIC Educational Resources Information Center

    Nye, William P.

    When Delta blues are considered to be "folk music," the genre is inextricably tied to the neocolonial, sharecropping system of cotton production characteristic of the Mississippi Delta region between the Civil War and World War II. "Imperialist nostalgia," then, arises in accounts which pay primary and positive tribute to blues…

  19. Wave-angle control of delta evolution

    NASA Astrophysics Data System (ADS)

    Ashton, Andrew D.; Giosan, Liviu

    2011-07-01

    Wave-influenced deltas, with large-scale arcuate shapes and demarcated beach ridge complexes, often display an asymmetrical form about their river channel. Here, we use a numerical model to demonstrate that the angles from which waves approach a delta can have a first-order influence upon its plan-view morphologic evolution and sedimentary architecture. The directional spread of incoming waves plays a dominant role over fluvial sediment discharge in controlling the width of an active delta lobe, which in turn affects the characteristic rates of delta progradation. Oblique wave approach (and a consequent net alongshore sediment transport) can lead to the development of morphologic asymmetry about the river in a delta's plan-view form. This plan-form asymmetry can include the development of discrete breaks in shoreline orientation and the appearance of self-organized features arising from shoreline instability along the downdrift delta flank, such as spits and migrating shoreline sand waves—features observed on natural deltas. Somewhat surprisingly, waves approaching preferentially from one direction tend to increase sediment deposition updrift of the river. This ‘morphodynamic groin effect’ occurs when the delta's plan-form aspect ratio is sufficiently large such that the orientation of the shoreline on the downdrift flank is rotated past the angle of maximum alongshore sediment transport, resulting in preferential redirection of fluvial sediment updrift of the river mouth.

  20. SF Bay Delta TMDL Progress Assessment

    EPA Pesticide Factsheets

    EPA assessed the progress 14 TMDLs in the SF Bay Delta Estuary (SF Bay Delta) to determine if the actions called for in the TMDL were being accomplished and water quality was improving. Status and water quality reports can be found here.

  1. Immunogenicity of Staphylococcus aureus delta-toxin.

    PubMed Central

    Nolte, F S; Kapral, F A

    1981-01-01

    Studies were conducted to determine the immunogenicity of purified Staphylococcus aureus delta-toxin. Rabbits and guinea pigs immunized with delta-toxin incorporated into a multiple antibody, whereas animals given toxin in saline or toxin in saline with Tween 80 did not produce antibody. The immunoglobulin G (IgG) fraction isolated by chromatography on protein A-Sepharose was examined for the presence of anti-delta-toxin antibody by immunoelectrophoresis, immunodiffusion, quantitative precipitation tests, affinity chromatography, and toxin neutralization tests. Although delta-toxin-specific IgG precipitated the toxin in agar gels, the antibody did not neutralize the toxin's hemolytic activity. Delta-toxin binding to human erythrocyte membranes was demonstrated by indirect immunofluorescent staining of toxin-treated erythrocytes. Images PMID:7014461

  2. Delta connected resonant snubber circuit

    DOEpatents

    Lai, J.S.; Peng, F.Z.; Young, R.W. Sr.; Ott, G.W. Jr.

    1998-01-20

    A delta connected, resonant snubber-based, soft switching, inverter circuit achieves lossless switching during dc-to-ac power conversion and power conditioning with minimum component count and size. Current is supplied to the resonant snubber branches solely by the dc supply voltage through the main inverter switches and the auxiliary switches. Component count and size are reduced by use of a single semiconductor switch in the resonant snubber branches. Component count is also reduced by maximizing the use of stray capacitances of the main switches as parallel resonant capacitors. Resonance charging and discharging of the parallel capacitances allows lossless, zero voltage switching. In one embodiment, circuit component size and count are minimized while achieving lossless, zero voltage switching within a three-phase inverter. 36 figs.

  3. Delta connected resonant snubber circuit

    DOEpatents

    Lai, Jih-Sheng; Peng, Fang Zheng; Young, Sr., Robert W.; Ott, Jr., George W.

    1998-01-01

    A delta connected, resonant snubber-based, soft switching, inverter circuit achieves lossless switching during dc-to-ac power conversion and power conditioning with minimum component count and size. Current is supplied to the resonant snubber branches solely by the dc supply voltage through the main inverter switches and the auxiliary switches. Component count and size are reduced by use of a single semiconductor switch in the resonant snubber branches. Component count is also reduced by maximizing the use of stray capacitances of the main switches as parallel resonant capacitors. Resonance charging and discharging of the parallel capacitances allows lossless, zero voltage switching. In one embodiment, circuit component size and count are minimized while achieving lossless, zero voltage switching within a three-phase inverter.

  4. Hepatitis Testing: MedlinePlus Health Topic

    MedlinePlus

    ... Resources Hepatitis A Test (American Association for Clinical Chemistry) Hepatitis B Test (American Association for Clinical Chemistry) Hepatitis C Test (American Association for Clinical Chemistry) ...

  5. Novel six-nucleotide deletion in the hepatic fructose-1,6-bisphosphate aldolase gene in a patient with hereditary fructose intolerance and enzyme structure-function implications.

    PubMed

    Santamaria, R; Vitagliano, L; Tamasi, S; Izzo, P; Zancan, L; Zagari, A; Salvatore, F

    1999-01-01

    Hereditary fructose intolerance (HFI) is an autosomal recessive human disease that results from the deficiency of the hepatic aldolase isoenzyme. Affected individuals will succumb to the disease unless it is readily diagnosed and fructose eliminated from the diet. Simple and non-invasive diagnosis is now possible by direct DNA analysis that scans for known and unknown mutations. Using a combination of several PCR-based methods (restriction enzyme digestion, allele specific oligonucleotide hybridisation, single strand conformation analysis and direct sequencing) we identified a novel six-nucleotide deletion in exon 6 of the aldolase B gene (delta 6ex6) that leads to the elimination of two amino acid residues (Leu182 and Val183) leaving the message inframe. The three-dimensional structural alterations induced in the enzyme by delta 6ex6 have been elucidated by molecular graphics analysis using the crystal structure of the rabbit muscle aldolase as reference model. These studies showed that the elimination of Leu182 and Val183 perturbs the correct orientation of adjacent catalytic residues such as Lys146 and Glu187.

  6. Geomorphologic model for Mississippi delta evolution

    SciTech Connect

    Boyd, R.; Penland, S.

    1988-09-01

    The Holocene Mississippi delta is over 9000 years old. During this time, the Mississippi River has established six delta complexes. Sediments are currently supplied only to two of these complexes, neither of which is more than 500 years old. Deltaic sedimentation during most of the Holocene has occurred in shoal-water deltas, unlike the modern Balize lobe, which is located at the shelf break. Mississippi delta sedimentation is cyclic and consists of a regressive and a transgressive phase. Each delta complex first experiences progradation until overextension leads to abandonment and reworking. Mississippi deltas undergoing transgression are dominated by subsidence and marine basin processes leading to the formation of sandy barriers and lagoons. Each of the six delta complexes followed a common pattern of development. Current delta geomorphology reflects the variation in age of each delta complex and can be summarizes in a three-stage model beginning with stage 1: erosional headland and flanking barriers. Here, distributary sands are reworked by the retreating shoreface and dispersed laterally by longshore transport into flanking barriers which enclose interdistributary bays. In stage 2, transgressive barrier island arc, submergence of the erosional headland generates an intradeltaic lagoon that separates the barrier island arc from the retreating mainland. The model ends with stage 3, inner shelf shoals, where the retreating barrier-island arc is unable to keep pace with relative sea level rise or the more rapidly retreating mainland. This stage results in submergence of the barrier-island arc, which continues to be reworked as a sandy shoal on the inner continental shelf. This model of delta evolution illustrates mechanisms for generation of both barrier islands (in stages 1 and 2) and continental shelf sand bodies (in stage 3).

  7. Feature Hepatitis: The Dangers of Hepatitis: What you should know from A to E

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Feature Hepatitis The Dangers of Hepatitis: What you should know from A to E ... drugs. In some cases, hepatitis lasts a lifetime. Hepatitis: Acute or Chronic? Acute hepatitis is the initial ...

  8. Viral hepatitis and hepatitis B antigen: recent advances

    PubMed Central

    Krugman, Saul

    1974-01-01

    Recent advances in hepatitis research have shed new light on the etiology, pathogenesis, epidemiology and prevention of type B hepatitis infection. The so-called ‘Dane’ particle is probably the complete hepatitis B virion; its outer coat is the hepatitis B (Australia) antigen (HB Ag) and its inner core is an immunologically distinct particle. Subtypes of HB Ag (a, d, y, w and r) are useful indices for epidemiological surveys. Concepts of epidemiology have changed: type B hepatitis is transmissible by contact as well as by inoculation. The presence of HB Ag in blood is indicative of the presence of hepatitis B virus. Tests to detect antigen and use of voluntary blood donors have played a major role in the decreased incidence of post transfusion hepatitis. A special hepatitis B gammaglobulin preparation and a heat-inactivated hepatitis B vaccine have proved to be effective in preliminary studies. PMID:4219230

  9. 78 FR 53127 - Delta-Bienville Resource Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-28

    ...; ] DEPARTMENT OF AGRICULTURE Forest Service Delta-Bienville Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. Date change. SUMMARY: The Delta-Bienville Resource Advisory...

  10. Relationships between hepatic trace element concentrations, reproductive status, and body condition of female greater scaup

    USGS Publications Warehouse

    Badzinski, S.S.; Flint, P.L.; Gorman, K.B.; Petrie, S.A.

    2009-01-01

    We collected female greater scaup (Aythya marila) on the Yukon-Kuskokwim Delta, Alaska during two breeding seasons to determine if concentrations of 18 trace elements in livers and eggs were elevated and if hepatic concentrations correlated with body condition or affected reproductive status. Fifty-six percent, 5%, and 42% of females, respectively, had elevated hepatic cadmium (Cd: >3 ??g g-1 dry weight [dw]), mercury (Hg: >3 ??g g-1 dw), and selenium (Se: >10 ??g g-1 dw). Somatic protein and lipid reserves were not correlated with hepatic Cd or Hg, but there was a weak negative correlation between protein and Se. Hepatic Cd, Hg, and Se were similar in females that had and had not initiated egg production. In a sample of six eggs, 33% and 100%, respectively, contained Se and Hg, but concentrations were below embryotoxicity thresholds. We conclude that trace element concentrations documented likely were not adversely impacting this study population. ?? 2009 Elsevier Ltd.

  11. Influence of different organic fertilizers on quality parameters and the delta(15)N, delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of orange fruit (Citrus sinensis L. Osbeck).

    PubMed

    Rapisarda, Paolo; Camin, Federica; Fabroni, Simona; Perini, Matteo; Torrisi, Biagio; Intrigliolo, Francesco

    2010-03-24

    To investigate the influence of different types of fertilizers on quality parameters, N-containing compounds, and the delta(15)N, delta(13)C, delta(2)H, delta (34)S, and delta(18)O values of citrus fruit, a study was performed on the orange fruit cv. 'Valencia late' (Citrus sinensis L. Osbeck), which was harvested in four plots (three organic and one conventional) located on the same farm. The results demonstrated that different types of organic fertilizers containing the same amount of nitrogen did not effect important changes in orange fruit quality parameters. The levels of total N and N-containing compounds such as synephrine in fruit juice were not statistically different among the different treatments. The delta(15)N values of orange fruit grown under fertilizer derived from animal origin as well as from vegetable compost were statistically higher than those grown with mineral fertilizer. Therefore, delta(15)N values can be used as an indicator of citrus fertilization management (organic or conventional), because even when applied organic fertilizers are of different origins, the natural abundance of (15)N in organic citrus fruit remains higher than in conventional ones. These treatments also did not effect differences in the delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of fruit.

  12. Hepatitis B Vaccination Protection

    MedlinePlus

    ... Protection Hepatitis B virus (HBV) is a pathogenic microorganism that can cause potentially life- threatening disease in ... bloodbornepathogens/index.html. To file a complaint by phone, report an emergency, or get OSHA advice, assistance, ...

  13. Hepatitis C and Incarceration

    MedlinePlus

    ... the Hepatitis Cvirus? Bleaching, boiling, heating with a flame, or using common cleaning fluids, alcohol, or peroxide ... Cbe treated? Yes, but not everyone needs medical treatment or can benefit from it. If possible, it ...

  14. Travelers' Health: Hepatitis E

    MedlinePlus

    ... by hepatitis E virus (HEV), a single-stranded, RNA virus belonging to the Hepeviridae family. TRANSMISSION HEV ... HEV IgM and IgG in serum. Detecting HEV RNA in serum or stools further confirms the serologic ...

  15. Alcohol and Hepatitis

    MedlinePlus

    ... code here Enter ZIP code here Daily Living: Alcohol for Veterans and the Public Alcohol and Hepatitis: Entire Lesson Overview Alcohol is one ... related to choices you make about your lifestyle . Alcohol and fibrosis Fibrosis is the medical term for ...

  16. Aggressive hepatitis (image)

    MedlinePlus

    Chronic active hepatitis is a liver disease caused by infection, drug ingestion, metabolic or autoimmune disorders. Necrosis (death) of liver cells, inflammation and fibrosis may lead to liver failure. Death within 5 years of onset occurs in ...

  17. Minimal hepatic encephalopathy.

    PubMed

    Zamora Nava, Luis Eduardo; Torre Delgadillo, Aldo

    2011-06-01

    The term minimal hepatic encephalopathy (MHE) refers to the subtle changes in cognitive function, electrophysiological parameters, cerebral neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and fluid homeostasis that can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy; the prevalence is as high as 84% in patients with hepatic cirrhosis. Physician does generally not perceive cirrhosis complications, and neuropsychological tests and another especial measurement like evoked potentials and image studies like positron emission tomography can only make diagnosis. Diagnosis of minimal hepatic encephalopathy may have prognostic and therapeutic implications in cirrhotic patients. The present review pretends to explore the clinic, therapeutic, diagnosis and prognostic aspects of this complication.

  18. Management of hepatic injury.

    PubMed Central

    Hanna, S. S.; Jirsch, D. W.

    1977-01-01

    Liver injuries may be due to either blunt or penetrating trauma to the thorax or abdomen. Specific treatment depends on the site and extent of hepatic injury. Following resuscitation with intravenous fluids and blood as needed, surgical therapy is directed to provide hemostasis, remove necrotic liver tissue and promote adequate external drainage in the postoperative period. While local measures are usually sufficient, complex hepatic wounds may require extensive resection and vascular ligature or repair. PMID:890631

  19. Identifying hazards associated with lava deltas

    USGS Publications Warehouse

    Poland, Michael P.; Orr, Tim R.

    2014-01-01

    Lava deltas, formed where lava enters the ocean and builds a shelf of new land extending from the coastline, represent a significant local hazard, especially on populated ocean island volcanoes. Such structures are unstable and prone to collapse—events that are often accompanied by small explosions that can deposit boulders and cobbles hundreds of meters inland. Explosions that coincide with collapses of the East Lae ‘Apuki lava delta at Kīlauea Volcano, Hawai‘i, during 2005–2007 followed an evolutionary progression mirroring that of the delta itself. A collapse that occurred when the lava–ocean entry was active was associated with a blast of lithic blocks and dispersal of spatter and fine, glassy tephra. Shortly after delta growth ceased, a collapse exposed hot rock to cold ocean water, resulting in an explosion composed entirely of lithic blocks and lapilli. Further collapse of the delta after several months of inactivity, by which time it had cooled significantly, resulted in no recognizable explosion deposit. Seaward displacement and subsidence of the coastline immediately inland of the delta was measured by both satellite and ground-based sensors and occurred at rates of several centimeters per month even after the lava–ocean entry had ceased. The anomalous deformation ended only after complete collapse of the delta. Monitoring of ground deformation may therefore provide an indication of the potential for delta collapse, while the hazard associated with collapse can be inferred from the level of activity, or the time since the last activity, on the delta.

  20. Immigration and viral hepatitis.

    PubMed

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO 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 iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants.

  1. Mechanisms of Hepatic Fibrogenesis

    PubMed Central

    Friedman, Scott L.

    2010-01-01

    Substantial improvements in the treatment of chronic liver disease have accelerated interest in uncovering the mechanisms underlying hepatic fibrosis and its resolution. Activation of resident hepatic stellate cells into proliferative, contractile, and fibrogenic cells in liver injury remains a dominant theme driving the field. However, several new areas of rapid progress in the past 5–10 years also have taken root, including: (1) identification of different fibrogenic populations apart from resident stellate cells, for example, portal fibroblasts, fibrocytes, and bone-marrow– derived cells, as well as cells derived from epithelial mesenchymal transition; (2) emergence of stellate cells as finely regulated determinants of hepatic inflammation and immunity; (3) elucidation of multiple pathways controlling gene expression during stellate cell activation including transcriptional, post-transcriptional, and epigenetic mechanisms; (4) recognition of disease-specific pathways of fibrogenesis; (5) re-emergence of hepatic macrophages as determinants of matrix degradation in fibrosis resolution and the importance of matrix cross-linking and scar maturation in determining reversibility; and (6) hints that hepatic stellate cells may contribute to hepatic stem cell behavior, cancer, and regeneration. Clinical and translational implications of these advances have become clear, and have begun to impact significantly on the management and outlook of patients with chronic liver disease. PMID:18471545

  2. Hepatitis B FAQs for the Public

    MedlinePlus

    ... Professional Resources Patient Education Resources Quick Links to Hepatitis … A | B | C | D | E Viral Hepatitis Home ... Grantees Policy and Programs Resource Center Viral Hepatitis Hepatitis B FAQs for the Public Recommend on Facebook ...

  3. Surveillance for Viral Hepatitis - United States, 2014

    MedlinePlus

    ... Historical reported cases and estimates Quick Links to Hepatitis … A | B | C | D | E Viral Hepatitis Home ... Programs Resource Center Viral Hepatitis Surveillance for Viral Hepatitis – United States, 2014 Recommend on Facebook Tweet Share ...

  4. Hepatitis C FAQs for the Public

    MedlinePlus

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

  5. Viral Hepatitis: A through E and Beyond

    MedlinePlus

    ... travelers How can hepatitis B be prevented? The hepatitis B vaccine offers the best pro tection. All infants and ... should receive hepatitis B immune globulin and the hepatitis B vaccine within 12 hours of birth to help prevent ...

  6. Hepatitis B virus infection in immigrant populations

    PubMed Central

    Coppola, Nicola; Alessio, Loredana; Pisaturo, Mariantonietta; Macera, Margherita; Sagnelli, Caterina; Zampino, Rosa; Sagnelli, Evangelista

    2015-01-01

    Hepatitis B virus (HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen (HBsAg) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBsAg-positive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention. PMID:26730274

  7. Recurrent hepatitis C after liver transplant

    PubMed Central

    deLemos, Andrew S; Schmeltzer, Paul A; Russo, Mark W

    2014-01-01

    End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5B polymerase inhibitors and NS5A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients. PMID:25152571

  8. Fulminant herpes hepatitis mimicking hepatic abscesses.

    PubMed

    Wolfsen, H C; Bolen, J W; Bowen, J L; Fenster, L F

    1993-01-01

    Fulminant hepatitis due to herpes simplex virus (HSV) in adults is a rare and deadly disease. We describe a 23-year-old woman with a 20-year history of Crohn's disease (CD) who was hospitalized with an acute febrile illness and diarrhea. A computed tomography (CT) scan of the abdomen demonstrated an intramural sigmoid colon abscess and multiple abscesses in the liver. Despite high-dose parenteral corticosteroids and broad-spectrum antibiotics, the patient remained acutely ill, with high fever and markedly elevated serum transaminase levels, but no jaundice. Sigmoid resection and wedge liver biopsy were performed at laparotomy. Histologic examination documented HSV-type intranuclear inclusions and inflammation with necrosis in both the sigmoid colon and liver specimens. The patient subsequently died despite parenteral acyclovir treatment. Although rare, fulminant hepatitis due to HSV simplex virus should be considered in the differential diagnosis of all patients with severe hepatitis. Of special note, the necrotizing liver lesions may be mistaken for pyogenic abscesses on CT scan.

  9. Novel diazabicycloalkane delta opioid agonists.

    PubMed

    Loriga, Giovanni; Lazzari, Paolo; Manca, Ilaria; Ruiu, Stefania; Falzoi, Matteo; Murineddu, Gabriele; Bottazzi, Mirko Emilio Heiner; Pinna, Giovanni; Pinna, Gérard Aimè

    2015-09-01

    Here we report the investigation of diazabicycloalkane cores as potential new scaffolds for the development of novel analogues of the previously reported diazatricyclodecane selective delta (δ) opioid agonists, as conformationally constrained homologues of the reference δ agonist (+)-4-[(αR)-α((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80). In particular, we have simplified the diazatricyclodecane motif of δ opioid agonist prototype 1a with bridged bicyclic cores. 3,6-diazabicyclo[3.1.1]heptane, 3,8-diazabicyclo[3.2.1]octane, 3,9-diazabicyclo[3.3.1]nonane, 3,9-diazabicyclo[4.2.1]nonane, and 3,10-diazabicyclo[4.3.1]decane were adopted as core motifs of the novel derivatives. The compounds were synthesized and biologically assayed as racemic (3-5) or diastereoisomeric (6,7) mixtures. All the novel compounds 3-7 showed δ agonism behaviour and remarkable affinity to δ receptors. Amongst the novel derivatives, 3,8-diazabicyclo[3.2.1]octane based compound 4 evidenced improved δ affinity and selectivity relative to SNC80.

  10. Delta Electroproduction in 12-C

    SciTech Connect

    McLauchlan, Steven

    2003-01-01

    The Δ-nucleus potential is a crucial element in the understanding of the nuclear system. Previous electroexcitation measurements in the delta region reported a Q2 dependence of the Δ mass indicating that this potential is dependent on the momentum of the Δ. Such a dependence is not observed for protons and neutrons in the nuclear medium. This thesis presents the experimental study of the electroexcitation of the Δ resonance in 12C, performed using the high energy electron beam at the Thomas Jefferson National Accelerator Facility, and the near 4π acceptance detector CLAS that enables the detection of the full reaction final state. Inclusive, semi inclusive, and exclusive cross sections were measured with an incident electron beam energy of 1.162GeV over the Q2 range 0.175-0.475 (GeV/c)2. A Q2 dependence of the Δ mass was only observed in the exclusive measurements indicating that the Δ-nucleus potential is affected by the momentum of the Δ.

  11. Hepatic encephalopathy associated with hepatic lipidosis in llamas (Lama glama).

    PubMed

    Pillitteri, C A; Craig, L E

    2013-01-01

    Hepatic encephalopathy has been listed as a differential for llamas displaying neurologic signs, but it has not been histopathologically described. This report details the neurologic histopathologic findings associated with 3 cases of hepatic lipidosis with concurrent neurologic signs and compares them to 3 cases of hepatic lipidosis in the absence of neurologic signs and 3 cases without hepatic lipidosis. Brain from all 3 llamas displaying neurologic signs contained Alzheimer type II cells, which were not detected in either subset of llamas without neurologic signs. Astrocytic immunohistochemical staining intensity for glial fibrillary acid protein was decreased in llamas with neurologic signs as compared to 2 of 3 llamas with hepatic lipidosis and without neurologic signs and to 2 of 3 llamas without hepatic lipidosis. Immunohistochemical staining for S100 did not vary between groups. These findings suggest that hepatic encephalopathy may be associated with hepatic lipidosis in llamas.

  12. Delta-nucleus dynamics: proceedings of symposium

    SciTech Connect

    Lee, T.S.H.; Geesaman, D.F.; Schiffer, J.P.

    1983-10-01

    The appreciation of the role in nuclear physics of the first excited state of the nucleon, the delta ..delta..(1232), has grown rapidly in the past decade. The delta resonance dominates nuclear reactions induced by intermediate energy pions, nucleons, and electromagnetic probes. It is also the most important non-nucleonic degree of freedom needed to resolve many fundamental problems encountered in the study of low-energy nuclear phenomena. Clearly, a new phase of nuclear physics has emerged and conventional thinking must be extended to account for this new dimension of nuclear dynamics. The most challenging problem we are facing is how a unified theory can be developed to describe ..delta..-nucleus dynamics at all energies. In exploring this new direction, it is important to have direct discussions among researchers with different viewpoints. Separate entries were prepared for the 49 papers presented. (WHK)

  13. Damped Oscillator with Delta-Kicked Frequency

    NASA Technical Reports Server (NTRS)

    Manko, O. V.

    1996-01-01

    Exact solutions of the Schrodinger equation for quantum damped oscillator subject to frequency delta-kick describing squeezed states are obtained. The cases of strong, intermediate, and weak damping are investigated.

  14. Contemporary depositional environments of the Omo delta.

    PubMed

    Butzer, K W

    1970-05-02

    Geomorphological and sedimentological studies of depositional environments of the modern Omo River delta and floodplain are essential to an understanding of the Pliocene to Pleistocene Mursi, Nkalabong and Kibish Formations of the Lower Omo Basin (southwestern Ethiopia).

  15. Migration in Vulnerable Deltas: A Research Strategy

    NASA Astrophysics Data System (ADS)

    Hutton, C.; Nicholls, R. J.; Allan, A.

    2015-12-01

    C. Hutton1, & R. J. Nicholls1, , 1 University of Southampton, University Road, Southampton, Hampshire, United Kingdom, SO17 1BJ. cwh@geodata. soton.ac.ukAbstractGlobally, deltas contain 500 million people and with rising sea levels often linked to large number of forced migrants are expected in the coming century. However, migration is already a major process in deltas, such as the growth of major cities such as Dhaka and Kolkata. Climate and environmental change interacts with a range of catchment and delta level drivers, which encompass a nexus of sea-level rise, storms, freshwater and sediment supply from the catchment, land degradation, subsidence, agricultural loss and socio-economic stresses. DECCMA (Deltas, Vulnerability and Climate Change: Migration and Adaptation/CARRIA) is investigating migration in the Ganges-Brahmaputra-Meghna (GBM), Mahanadi and Volta Deltas, including the influence of climate change. The research will explore migration from a range of perspectives including governance and stakeholder analysis, demographic analysis, household surveys of sending and receiving areas, macro-economic analysis, and hazards and hotspot analysis both historically and into the future. Migration under climate change will depend on other adaptation in the deltas and this will be examined. Collectively, integrated analysis will be developed to examine migration, other adaptation and development pathways with a particular focus on the implications for the poorest. This will require the development of input scenarios, including expert-derived exogenous scenarios (e.g., climate change) and endogenous scenarios of the delta developed in a participatory manner. This applied research will facilitate decision support methods for the development of deltas under climate change, with a focus on migration and other adaptation strategies.

  16. Lena River delta formation during the Holocene

    NASA Astrophysics Data System (ADS)

    Bolshiyanov, D.; Makarov, A.; Savelieva, L.

    2015-01-01

    The Lena River delta, the largest delta of the Arctic Ocean, differs from other deltas because it consists mainly of organomineral sediments, commonly called peat, that contain a huge organic carbon reservoir. The analysis of delta sediment radiocarbon ages showed that they could not have formed as peat during floodplain bogging; rather, they accumulated when Laptev Sea water level was high and green mosses and sedges grew and were deposited on the surface of flooded marshes. The Lena River delta formed as organomineral masses and layered sediments accumulated during transgressive phases when sea level rose. In regressive phases, the islands composed of these sediments and other, more ancient islands were eroded. Each new sea transgression led to further accumulation of layered sediments. As a result of alternating transgressive and regressive phases, the first alluvial-marine terrace formed, consisting of geological bodies of different ages. Determining the formation age of different areas of the first terrace and other marine terraces on the coast allowed the periods of increasing (8000-6000 BP (years before present), 4500-4000, 2500-1500, and 400-200 BP) and decreasing (5000, 3000, and 500 BP) Laptev Sea levels to be distinguished in the Lena Delta area.

  17. Preparing Nimbus E on Delta Vehicle

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Nimbus E, the sixth spacecraft in the Nimbus series, is shown preparing for launch on December 12, 1972 from the Western Test Range (WTR), Space Launch Complex SLC-2, West, by the Thrust- Augmented Delta vehicle. The satellite was placed in an 1100-kilometer run-synchronous nearly circular polar orbit. The spacecraft was designated Nimbus 5 upon confirmation that it had achieved successful orbit. The Delta launch vehicle family started development in 1959. The Delta is composed of parts from the Thor, an intermediate-range ballistic missile, as its first stage, and the Vanguard as its second. The first Delta was launched from Cape Canaveral on May 13, 1960 and was powerful enough to deliver a 100-pound spacecraft into geostationary transfer orbit. Delta has been used to launch civil, commercial, and military satellites into orbit. For more information about Delta, please see Chapter 3 in Roger Launius and Dennis Jenkins' book To Reach the High Frontier published by The University Press of Kentucky in 2002.

  18. FastStats: Viral Hepatitis

    MedlinePlus

    ... Submit What's this? Submit Button NCHS Home Viral Hepatitis Recommend on Facebook Tweet Share Compartir Data are for the U.S. Morbidity Number of new hepatitis A cases: 1,781 (2013) Number of new ...

  19. Diabetes and Hepatitis B Vaccination

    MedlinePlus

    ... monitoring in close succession. CDC now recommends the hepatitis B vaccine for adults with diabetes. What is the recommendation ... As with other vaccines, the effectiveness of the hepatitis B vaccine decreases with age. Decisions to vaccinate should include ...

  20. Sea urchin elongation factor 1delta (EF1delta) and evidence for cell cycle-directed localization changes of a sub-fraction of the protein at M phase.

    PubMed

    Boulben, S; Monnier, A; Le Breton, M; Morales, J; Cormier, P; Bellé, R; Mulner-Lorillon, O

    2003-10-01

    Eukaryotic elongation factor 1 (eEF1) is a translational multimolecular complex reported in higher eukaryotes to be a target of CDK1/cyclin B, the universal regulator of M phase, but whose role in the cell cycle remains to be determined. A specific polyclonal antibody was produced and used to characterize the delta subunit of sea urchin elongation factor 1 (SgEF1delta) in early embryos, a powerful model for investigating cell cycle regulation. The SgEF1delta protein was present in unfertilized eggs as two isoforms of 35 and 37 kDa, issued from two different mRNAs. The two canonical eEF1delta partners, eEF1gamma and eEF1beta, were shown to co-immunoprecipitate with the SgEF1delta isoforms. Both isoforms were associated in a macromolecular complex, which resolved upon gel filtration chromatography at a molecular weight > 400 kDa, suggesting association with other yet unidentified partners. After fertilization, the amount as well as the ratio of both SgEF1delta isoforms remained constant during the first cell division as judged by Western blotting. Immunofluorescence analysis showed that a pool of the protein concentrated as a ring at the embryo nuclear location around the period of nuclear envelope breakdown and was visualized later as two large spheres around the mitotic spindle poles. Thus, the eEF1delta protein shows cell cycle-specific localization changes in sea urchin embryos.

  1. Pregnancy with autoimmune hepatitis

    PubMed Central

    Braga, António Costa; Vasconcelos, Carlos; Braga, Jorge

    2016-01-01

    Aim: The aim of this study was to review our experience with gestations in autoimmune hepatitis patients. Background: There are only limited data describing pregnancy in patients with autoimmune hepatitis. Patients and methods: Retrospective analysis of pregnancies with autoimmune hepatitis followed in Centro Hospitalar do Porto, Portugal in the last ten years. Results: We reported nine pregnancies in seven patients with autoimmune hepatitis. Two patients had documented liver cirrhosis prior to the pregnancy. In this study, 66.7% of patients were treated with azathioprine and 88.9% with prednisolone. Clinical improvements were observed in 11.1% of pregnancies and 22.2% exacerbations were diagnosed. There were six live births and two preterm deliveries (preterm delivery rate of 33%). We also report three first trimester miscarriages (early gestation miscarriage rate of 33%). There were no neonatal or maternal deaths. Conclusion: The favorable obstetric outcome is a realistic expectation in patients with autoimmune hepatitis. Tight monitoring and control of asymptomatic and unpredictable exacerbations, which are unrelated to the severity of the underlying disease, are essential to the prognosis of the current pregnancy. PMID:27458515

  2. Hepatic hemangioma -review-.

    PubMed

    Bajenaru, N; Balaban, V; Săvulescu, F; Campeanu, I; Patrascu, T

    2015-01-01

    Hepatic hemangiomas are benign tumors of the liver consisting of clusters of blood-filled cavities, lined by endothelial cells, fed by the hepatic artery. The vast majority of HH are asymptomatic, most often being discovered incidentally during imaging investigations for various unrelated pathologies. Typical hemangiomas, the so-called capillary hemangiomas, range from a few mm to 3 cm, do not increase in size over time and therefore are unlikely to generate future symptomatology. Small (mm-3 cm) and medium (3 cm-10 cm) hemangiomas are well-defined lesions, requiring no active treatment beside regular follow-ups. However, the so-called giant liver hemangiomas, of up to 10 cm (most commonly) and even 20+ cm in size (according to occasional reports) can, and usually will develop symptoms and complications that require prompt surgical intervention or other kind of therapy. HH belong to the class of hepatic "incidentalomas", so-called because they are diagnosed incidentally, on imaging studies performed as routine examinations or for other reasons than the evaluation of a possible liver mass. Less than half of HH present with overt clinical symptoms, consisting, most often, of upper abdominal pain (this is usually the case for large lesions, which cause the distension of Glisson's capsule). Hepatic hemangiomas require a careful diagnosis to differentiate from other focal hepatic lesions, co-occurring diagnoses are also possible.

  3. A novel mouse PKC{delta} splice variant, PKC{delta}IX, inhibits etoposide-induced apoptosis

    SciTech Connect

    Kim, Jung D.; Seo, Kwang W.; Lee, Eun A.; Quang, Nguyen N.; Cho, Hong R.; Kwon, Byungsuk

    2011-07-01

    Highlights: {yields} A novel PKC{delta} isoform, named PKC{delta}IX, that lacks the C1 domain and the ATP-binding site is ubiquitously expressed. {yields} PKC{delta}IX inhibits etoposide-induced apoptosis. {yields} PKC{delta}IX may function as an endogenous dominant negative isoform for PKC{delta}. -- Abstract: Protein kinase C (PKC) {delta} plays an important role in cellular proliferation and apoptosis. The catalytic fragment of PKC{delta} generated by caspase-dependent cleavage is essential for the initiation of etoposide-induced apoptosis. In this study, we identified a novel mouse PKC{delta} isoform named PKC{delta}IX (Genebank Accession No. (HQ840432)). PKC{delta}IX is generated by alternative splicing and is ubiquitously expressed, as seen in its full-length PKC{delta}. PKC{delta}IX lacks the C1 domain, the caspase 3 cleavage site, and the ATP binding site but preserves an almost intact c-terminal catalytic domain and a nuclear localization signal (NLS). The structural characteristics of PKC{delta}IX provided a possibility that this PKC{delta} isozyme functions as a novel dominant-negative form for PKC{delta} due to its lack of the ATP-binding domain that is required for the kinase activity of PKC{delta}. Indeed, overexpression of PKC{delta}IX significantly inhibited etoposide-induced apoptosis in NIH3T3 cells. In addition, an in vitro kinase assay showed that recombinant PKC{delta}IX protein could competitively inhibit the kinase activity of PKC{delta}. We conclude that PKC{delta}IX can function as a natural dominant-negative inhibitor of PKC{delta}in vivo.

  4. Long-distance communication in the HDV ribozyme: insights from molecular dynamics and experiments.

    PubMed

    Veeraraghavan, Narayanan; Bevilacqua, Philip C; Hammes-Schiffer, Sharon

    2010-09-10

    The hepatitis delta virus ribozyme is a small, self-cleaving RNA with a compact tertiary structure and buried active site that is important in the life cycle of the virus. The ribozyme's function in nature is to cleave an internal phosphodiester bond and linearize concatemers during rolling circle replication. Crystal structures of the ribozyme have been solved in both pre-cleaved and post-cleaved (product) forms and reveal an intricate network of interactions that conspire to catalyze bond cleavage. In addition, extensive biochemical studies have been performed to work out a mechanism for bond cleavage in which C75 and a magnesium ion catalyze the reaction by general acid-base chemistry. One issue that has remained unclear in this ribozyme and in other ribozymes is the nature of long-distance communication between peripheral regions of the RNA and the buried active site. We performed molecular dynamics simulations on the hepatitis delta virus ribozyme in the product form and assessed communication between a distal structural portion of the ribozyme-the protonated C41 base triple-and the active site containing the critical C75. We varied the ionization state of C41 in both the wild type and a C41 double mutant variant and determined the impact on the active site. In all four cases, effects at the active site observed in the simulations agree with experimental studies on ribozyme activity. Overall, these studies indicate that small functional RNAs have the potential to communicate interactions over long distances and that wild-type RNAs may have evolved ways to prevent such interactions from interfering with catalysis.

  5. Update on occult hepatitis B virus infection

    PubMed Central

    Makvandi, Manoochehr

    2016-01-01

    The event of mutations in the surface antigen gene of hepatitis B virus (HBV) results in undetectable hepatitis B surface antigen with positive/negative anti-hepatitis B core (anti-HBc) antibody status in serum and this phenomenon is named occult hepatitis B infection (OBI). The presence of anti-HBc antibody in serum is an important key for OBI tracking, although about 20% of OBI cases are negative for anti-HBc antibody. The diagnosis of OBI is mainly based on polymerase chain reaction (PCR) and real-time PCR assays. However, real-time PCR is a more reliable method than PCR. OBI is a great issue for the public health problem and a challenge for the clinical entity worldwide. The persistence of OBI may lead to the development of cirrhosis and hepatocellular carcinoma. With regard to OBI complications, the screening of HBV DNA by the highly sensitive molecular means should be implemented for: (1) patients with a previous history of chronic or acute HBV infection; (2) patients co-infected with hepatitis C virus/human immunodeficiency virus; (3) patients undergoing chemotherapy or anti-CD20 therapy; (4) recipients of organ transplant; (5) blood donors; (6) organ transplant donors; (7) thalassemia and hemophilia patients; (8) health care workers; (9) patients with liver related disease (cryptogenic); (10) hemodialysis patients; (11) patients undergoing lamivudine or interferon therapy; and (12) children in time of HBV vaccination especially in highly endemic areas of HBV. Active HBV vaccination should be implemented for the close relatives of patients who are negative for OBI markers. Thus, the goal of this review is to evaluate the rate of OBI with a focus on status of high risk groups in different regions of the world. PMID:27818588

  6. New diarylmethylpiperazines as potent and selective nonpeptidic delta opioid receptor agonists with increased In vitro metabolic stability.

    PubMed

    Plobeck, N; Delorme, D; Wei, Z Y; Yang, H; Zhou, F; Schwarz, P; Gawell, L; Gagnon, H; Pelcman, B; Schmidt, R; Yue, S Y; Walpole, C; Brown, W; Zhou, E; Labarre, M; Payza, K; St-Onge, S; Kamassah, A; Morin, P E; Projean, D; Ducharme, J; Roberts, E

    2000-10-19

    Nonpeptide delta opioid agonists are analgesics with a potentially improved side-effect and abuse liability profile, compared to classical opioids. Andrews analysis of the NIH nonpeptide lead SNC-80 suggested the removal of substituents not predicted to contribute to binding. This approach led to a simplified lead, N, N-diethyl-4-[phenyl(1-piperazinyl)methyl]benzamide (1), which retained potent binding affinity and selectivity to the human delta receptor (IC(50) = 11 nM, mu/delta = 740, kappa/delta > 900) and potency as a full agonist (EC(50) = 36 nM) but had a markedly reduced molecular weight, only one chiral center, and increased in vitro metabolic stability. From this lead, the key pharmacophore groups for delta receptor affinity and activation were more clearly defined by SAR and mutagenesis studies. Further structural modifications on the basis of 1 confirmed the importance of the N, N-diethylbenzamide group and the piperazine lower basic nitrogen for delta binding, in agreement with mutagenesis data. A number of piperazine N-alkyl substituents were tolerated. In contrast, modifications of the phenyl group led to the discovery of a series of diarylmethylpiperazines exemplified by N, N-diethyl-4-[1-piperazinyl(8-quinolinyl)methyl]benzamide (56) which had an improved in vitro binding profile (IC(50) = 0.5 nM, mu/delta = 1239, EC(50) = 3.6 nM) and increased in vitro metabolic stability compared to SNC-80.

  7. The Okavango: Whose Delta is it?

    NASA Astrophysics Data System (ADS)

    Magole, Lapologang; Magole, Lefatshe Innocent

    The Okavango Delta is amongst the largest Ramsar sites ( http://www.ramsar.org/sitelist.pdf) in the world and an important wetland for community livelihoods, conservation and tourism in Botswana. Over the years, the utilization of the delta has shifted from communal use to state control, with an increased use for conservation and tourism. This increased use for conservation and tourism has manifested in the physical expansion of the conservation area - Moremi Game Reserve and the formation of Wildlife Management Areas (WMAs) around the reserve, whose primary land use is wildlife utilization. The expansion of the conservation area has translated into several practical matters, including expansion of the area for non-hunting activities or photographic areas. The livelihoods of local communities of the Okavango delta who depended on fishing, hunter-gathering, livestock rearing, rain-fed agriculture and flood recession farming have been negatively affected by the expansion of conservation and tourism in the delta. The livelihoods alternatives in the form of Community Based Natural Resource Management (CBNRM) and tourism have not provided substitutes for the people as the communities are still reliant on the same old livelihood sources as in the past, albeit within smaller and restricted areas. This paper explores the ownership of the natural resources within the Okavango Delta. It asks and attempts to answer the following questions: Who owns and controls the use of the land? Who has access to other resources there in? Who makes the decisions on how the delta resources should be managed and used? Who benefits from the delta resources? We argue firstly that ownership of the delta as defined by legal parameters and demonstrated in natural resource management practice is vested on government. Secondly, government, after assuming ownership of the delta continues to sell its stake to the international community, at the expense of local ownership and access to resources. We

  8. Chromium-induced toxic hepatitis.

    PubMed

    Lança, Sara; Alves, Amanda; Vieira, Ana Isabel; Barata, José; de Freitas, João; de Carvalho, Alvaro

    2002-12-01

    A clinical case of acute hepatitis in a patient undergoing an alternative medicine weight-reduction regimen is reported. Chromium polynicotinate had been ingested in combination with vegetable extracts over a 5-month period. Liver biopsy was compatible with toxic hepatitis and greatly elevated hepatic chromium levels were found (>10x normal). The clinical picture regressed following suspension of the medication.

  9. Alcoholic hepatitis: current management.

    PubMed

    Spengler, Erin K J; Dunkelberg, Jeffrey; Schey, Ron

    2014-10-01

    Alcoholic hepatitis is an acute manifestation of alcoholic liver disease with mortality as high as 40-50% in severe cases. Patients usually have a history of prolonged alcohol abuse with or without a known history of liver disease. Although there is significant range in severity at presentation, patients with severe alcoholic hepatitis typically present with anorexia, fatigue, fever, jaundice, and ascites. The use of either pentoxifylline or corticosteroids in those with severe disease (Maddrey's discriminate function >32) has significant mortality benefit. The addition of N-acetylcysteine to corticosteroids decreases the incidences of hepatorenal syndrome, infection, and short-term mortality, but does not appear to significantly affect 6-month mortality. Nutritional support with high-calorie, high-protein diet is recommended in all patients screening positive for malnutrition. Liver transplantation for a highly selected group of patients with severe alcoholic hepatitis may be an option in the future, but is not currently recommended or available at most transplant institutions.

  10. Primary hepatic carcinoid tumor.

    PubMed

    Gao, Jinbo; Hu, Zhijian; Wu, Junwei; Bai, Lishan; Chai, Xinqun

    2011-11-19

    Primary hepatic carcinoid tumor is rare and poses a challenge for diagnosis and management. We presented a case of primary hepatic carcinoid tumor in a 53-year-old female with a complaint of right upper abdominal pain. Computer tomography scans revealed a hypervascular mass in segment 4 of the liver. An ultrasonography-guided biopsy showed a carcinoid tumor. No other lesions were found by the radiological investigations. Surgery resection was performed and histopathological examination revealed a primary hepatic carcinoid tumor. Three years later, recurrence was found and transcatheter arterial chemoembolization was performed. After transcatheter arterial chemoembolization, the patient has been free of symptom and had no radiological disease progression for over 6 months. Surgical resection combination with transcatheter arterial chemoembolization is effective to offer excellent palliation.

  11. [Hepatitis E as zoonosis].

    PubMed

    Baumann-Popczyk, Anna

    2011-01-01

    The hepatitis E virus (HEV) the causative agent of hepatitis E, is a non-enveloped RNA virus. HEV is transmitted through oral consumption of contaminated food and water According to the currently knowledge now be considered as zoonosis. The main reservoir of HEV are pigs, boars and deer. For the first time HEV was isolated from animals (pigs) in 1997 in the U.S. Genetic analysis of strains isolated from pigs showed high similarity to strains HEV isolated from humans. This was the first evidence showing that HEV is a zoonosis. Further studies have shown that occupational groups e.g. veterinarians, swine breeders with close contact to pigs have an increased risk for HEV infections. The additional evidence supported the zoonotic potential of HEV were reports of acute hepatitis E after the consumption of undercooked meat from deer and wild boar. Infection of HEV in the domestic pig and wild boar population in Europe is widespread.

  12. Neonatal hepatitis syndrome.

    PubMed

    Roberts, Eve A

    2003-10-01

    Conjugated hyperbilirubinaemia in an infant indicates neonatal liver disease. This neonatal hepatitis syndrome has numerous possible causes, classified as infective, anatomic/structural, metabolic, genetic, neoplastic, vascular, toxic, immune and idiopathic. Any infant who is jaundiced at 2-4 weeks old needs to have the serum conjugated bilirubin measured, even if he/she looks otherwise well. If conjugated hyperbilirubinaemia is present, a methodical and comprehensive diagnostic investigation should be performed. Early diagnosis is critical for the best outcome. In particular, palliative surgery for extrahepatic biliary atresia has the best chance of success if performed before the infant is 8 weeks old. Definitive treatments available for many causes of neonatal hepatitis syndrome should be started as soon as possible. Alternatively, liver transplantation may be life saving. Supportive care, especially with attention to nutritional needs, is important for all infants with neonatal hepatitis syndrome.

  13. JAM-A is both essential and inhibitory to development of hepatic polarity in WIF-B cells.

    PubMed

    Braiterman, Lelita T; Heffernan, Sean; Nyasae, Lydia; Johns, David; See, Alfred P; Yutzy, Rebeca; McNickle, Allison; Herman, Mira; Sharma, Arun; Naik, Ulhas P; Hubbard, Ann L

    2008-02-01

    Junctional adhesion molecule (JAM) is involved in tight junction (TJ) formation in epithelial cells. Three JAMs (A, B, and C) are expressed in rat hepatocytes, but only rat JAM-A is present in polarized WIF-B cells, a rat-human hepatic line. We used knockdown (KD) and overexpression in WIF-B cells to determine the role of JAM-A in the development of hepatic polarity. Expression of rat JAM-A short hairpin RNA resulted in approximately 50% KD of JAM-A and substantial loss of hepatic polarity, as measured by the absence of apical cysts formed by adjacent cells and sealed by TJ belts. When inhibitory RNA-resistant human JAM-A (huWT) was expressed in KD cells, hepatic polarity was restored. In contrast, expression of JAM-A that either lacked its PDZ-binding motif (huDeltaC-term) or harbored a point mutation (T273A) did not complement, indicating that multiple sites within JAM-A's cytoplasmic tail are required for the development of hepatic polarity. Overexpression of huWT in normal WIF-B cells unexpectedly blocked WIF-B maturation to the hepatic phenotype, as did expression of three huJAM-A constructs with single point mutations in putative phosphorylation sites. In contrast, huDeltaC-term was without effect, and the T273A mutant only partially blocked maturation. Our results show that JAM-A is essential for the development of polarity in cultured hepatic cells via its possible phosphorylation and recruitment of relevant PDZ proteins and that hepatic polarity is achieved within a narrow range of JAM-A expression levels. Importantly, formation/maintenance of TJs and the apical domain in hepatic cells are linked, unlike simple epithelia.

  14. Hepatitis G virus: is it a hepatitis virus?

    PubMed Central

    Cheung, R C; Keeffe, E B; Greenberg, H B

    1997-01-01

    Hepatitis G virus (HGV) and GB virus C (GBV-C) are two newly discovered viral agents, different isolates of a positive-sense RNA virus that represents a new genus of Flaviviridae. The purpose of this review is to analyze new data that have recently been published on the epidemiology and associations between HGV and liver diseases such as posttransfusion hepatitis, acute and chronic non-A-E hepatitis, fulminant hepatitis, cryptogenic cirrhosis, and hepatocellular carcinoma. The role of HGV in coinfection with other hepatitis viruses, the response to antiviral therapy, and the impact of HGV on liver transplantation are also discussed. HGV is a transmissible blood-borne viral agent that frequently occurs as a coinfection with other hepatitis viruses due to common modes of transmission. The prevalence of HGV ranges from 0.9 to 10% among blood donors throughout the world and is found in 1.7% of volunteer blood donors in the United States. The majority of patients infected with HGV by blood transfusion do not develop chronic hepatitis, but hepatitis G viremia frequently persists without biochemical evidence of hepatitis. Serum HGV RNA has been found in 0 to 50% of patients with fulminant hepatitis of unknown etiology and 14 to 36% of patients with cryptogenic cirrhosis. The association between HGV and chronic non-A-E hepatitis remains unclear. Although HGV appears to be a hepatotrophic virus, its role in independently causing acute and chronic liver diseases remains uncertain. PMID:9265860

  15. Model for the {Delta}(1600) resonance and {gamma}N{yields}{Delta}(1600) transition

    SciTech Connect

    Ramalho, G.; Tsushima, K.

    2010-10-01

    A covariant spectator constituent quark model is applied to study the {gamma}N{yields}{Delta}(1600) transition. Two processes are important in the transition: a photon couples to the individual quarks of the {Delta}(1600) core (quark core), and a photon couples to the intermediate pion-baryon states (pion cloud). While the quark core contributions are estimated assuming {Delta}(1600) as the first radial excitation of {Delta}(1232), the pion cloud contributions are estimated based on an analogy with the {gamma}N{yields}{Delta}(1232) transition. To estimate the pion cloud contributions in the {gamma}N{yields}{Delta}(1600) transition, we include the relevant intermediate states, {pi}N, {pi}{Delta}, {pi}N(1440) and {pi}{Delta}(1600). Dependence on the four-momentum transfer squared, Q{sup 2}, is predicted for the magnetic dipole transition form factor, G{sub M}*(Q{sup 2}), as well as the helicity amplitudes, A{sub 1/2}(Q{sup 2}) and A{sub 3/2}(Q{sup 2}). The results at Q{sup 2}=0 are compared with the existing data.

  16. A model for the Delta(1600) resonance and gamma N -> Delta(1600) transition

    SciTech Connect

    G. Ramalho, K. Tsushima

    2010-10-01

    A covariant spectator constituent quark model is applied to study the gamma N -> Delta(1600) transition. Two processes are important in the transition: a photon couples to the individual quarks of the Delta(1600) core (quark core), and a photon couples to the intermediate pion-baryon states (pion cloud). While the quark core contributions are estimated assuming Delta(1600) as the first radial excitation of Delta(1232), the pion cloud contributions are estimated based on an analogy with the gamma N -> Delta(1232) transition. To estimate the pion cloud contributions in the gamma N -> Delta(1600) transition, we include the relevant intermediate states, pi-N, pi-Delta, pi-N(1440) and pi-Delta(1600). Dependence on the four-momentum transfer squared, Q2, is predicted for the magnetic dipole transition form factor, GM*(Q2), as well as the helicity amplitudes, A_1/2(Q2) and A_3/2(Q2). The results at Q2=0 are compared with the existing data.

  17. Interdisciplinary and Distance Education in the Delta: The Delta Health Education Partnership.

    ERIC Educational Resources Information Center

    Skorga, Phyllis

    2002-01-01

    Describes the Delta Health Education Partnership, an interdisciplinary distance education program intended to recruit, educate, and retain interdisciplinary groups of primary care health practitioners to increase access to health care in medically underserved and health professional shortage areas of the lower Mississippi Delta. It spans six…

  18. Epidemiological study of viral hepatitis types A, B, C, D and E among Inuits in West Greenland.

    PubMed

    Langer, B C; Frösner, G G; von Brunn, A

    1997-09-01

    A descriptive study was performed to evaluate the relative frequencies and molecular epidemiological features of viral hepatitis types A to E among the Inuit population in West Greenland. Serum samples were collected from 503 Inuits (186 males and 317 females; mean age 35 years; range 7-79 years) and were tested for markers of viral hepatitis infection. The hepatitis A prevalence averaged 54%, with a significant rise from 9% to 50% between the second and third decade of life. As for hepatitis B, 42% of the total study population showed serological evidence of current or past hepatitis B virus (HBV) infection and 7% were hepatitis B surface antigen (HBsAg) carriers. Among the carriers, 6% were also positive for hepatitis B e antigen (HBeAg), and HBV DNA could be detected in 49% of carriers by polymerase chain reaction. Typing of the HBV isolates revealed genomic group D in 83% (serotype ayw2) and group A in 17% (serotype adw 2). Less than 1% of the study population had antibodies to the hepatitis C virus. None were positive for HCV RNA. Serological evidence of hepatitis D infection was found in 7% of those with hepatitis B helper virus infection markers and in 40% of the HBsAg carriers. As for hepatitis E, 3% of the Inuits showed reactivity in an enzyme immunoassay that detected hepatitis E virus antibody. HEV RNA could not be detected.

  19. The DELTA MONSTER: An RPV designed to investigate the aerodynamics of a delta wing platform

    NASA Technical Reports Server (NTRS)

    Connolly, Kristen; Flynn, Mike; Gallagher, Randy; Greek, Chris; Kozlowski, Marc; Mcdonald, Brian; Mckenna, Matt; Sellar, Rich; Shearon, Andy

    1989-01-01

    The mission requirements for the performance of aerodynamic tests on a delta wind planform posed some problems, these include aerodynamic interference; structural support; data acquisition and transmission instrumentation; aircraft stability and control; and propulsion implementation. To eliminate the problems of wall interference, free stream turbulence, and the difficulty of achieving dynamic similarity between the test and actual flight aircraft that are associated with aerodynamic testing in wind tunnels, the concept of the remotely piloted vehicle which can perform a basic aerodynamic study on a delta wing was the main objective for the Green Mission - the Delta Monster. The basic aerodynamic studies were performed on a delta wing with a sweep angle greater than 45 degrees. These tests were performed at various angles of attack and Reynolds numbers. The delta wing was instrumented to determine the primary leading edge vortex formation and location, using pressure measurements and/or flow visualization. A data acquisition system was provided to collect all necessary data.

  20. Hepatitis A transmitted by food.

    PubMed

    Fiore, Anthony E

    2004-03-01

    Hepatitis A is caused by hepatitis A virus (HAV). Transmission occurs by the fecal-oral route, either by direct contact with an HAV-infected person or by ingestion of HAV-contaminated food or water. Foodborne or waterborne hepatitis A outbreaks are relatively uncommon in the United States. However, food handlers with hepatitis A are frequently identified, and evaluation of the need for immunoprophylaxis and implementation of control measures are a considerable burden on public health resources. In addition, HAV-contaminated food may be the source of hepatitis A for an unknown proportion of persons whose source of infection is not identified.