Science.gov

Sample records for verisure pro hbv

  1. Hepatitis B (HBV)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Hepatitis B (HBV) KidsHealth > For Teens > Hepatitis B (HBV) Print A A A Text Size ... Prevented? How Is It Treated? What Is It? Hepatitis (pronounced: hep-uh-TIE-tiss) is a disease ...

  2. HBV culture and infectious systems.

    PubMed

    Hayes, C Nelson; Chayama, Kazuaki

    2016-07-01

    While an effective vaccine against hepatitis B virus (HBV) has long been available, chronic HBV infection remains a severe global public health concern. Current treatment options have limited effectiveness, and long-term therapy is required to suppress HBV replication; however, complete elimination of the virus is rare. The lack of suitable animal models and infection systems has hindered efforts to unravel the HBV life cycle, particularly the early events in HBV entry, which appear to be highly species- and tissue-specific. Human primary hepatocytes remain the gold standard for HBV replication studies but are limited by availability and variability. While the HepaRG cell line is permissive for HBV replication, other hepatoma cell lines such as HepG2 do not support HBV replication. The recent discovery of sodium taurocholate transporting peptide (NTCP) as a primary receptor for HBV binding has led to the development of replication-competent cell lines such as HepG2-NTCP. Human hepatocytes grown in chimeric mice have provided another approach that allows primary human hepatocytes to be used while overcoming many of their limitations. Although the difficulty in developing HBV infection systems has hindered development of effective treatments, the variability and limited replication efficiency among cell lines point to additional liver-specific factors involved in HBV infection. It is hoped that HBV infection studies will lead to novel drug targets and therapeutic options for the treatment of chronic HBV infection. PMID:26935052

  3. HBV cure: why, how, when?

    PubMed

    Levrero, Massimo; Testoni, Barbara; Zoulim, Fabien

    2016-06-01

    Current HBV treatments control replication and liver disease progression in the vast majority of treated patients. However, HBV patients often require lifelong therapies due to the persistence of transcriptionally active viral cccDNA mini-chromosome in the nucleus, which is not directly targeted by current antiviral therapies. A true complete cure of HBV would require clearance of intranuclear cccDNA from all infected hepatocytes. An intermediate but still relevant step forward that would allow treatment cessation would be reaching a functional cure, equivalent to resolved acute infection, with a durable HBsAg loss±anti-HBs seroconversion, undetectable serum DNA and persistence of cccDNA in a transcriptionally inactive status. Recent advances in technologies and pharmaceutical sciences, including the cloning of the mayor HBV receptor (i.e. the NTCP transporter) and the development in vitro HBV infection models, have heralded a new horizon of innovative antiviral and immune-therapeutic approaches. PMID:27447092

  4. HBV Genotypic Variability in Cuba

    PubMed Central

    Loureiro, Carmen L.; Aguilar, Julio C.; Aguiar, Jorge; Muzio, Verena; Pentón, Eduardo; Garcia, Daymir; Guillen, Gerardo; Pujol, Flor H.

    2015-01-01

    The genetic diversity of HBV in human population is often a reflection of its genetic admixture. The aim of this study was to explore the genotypic diversity of HBV in Cuba. The S genomic region of Cuban HBV isolates was sequenced and for selected isolates the complete genome or precore-core sequence was analyzed. The most frequent genotype was A (167/250, 67%), mainly A2 (149, 60%) but also A1 and one A4. A total of 77 isolates were classified as genotype D (31%), with co-circulation of several subgenotypes (56 D4, 2 D1, 5 D2, 7 D3/6 and 7 D7). Three isolates belonged to genotype E, two to H and one to B3. Complete genome sequence analysis of selected isolates confirmed the phylogenetic analysis performed with the S region. Mutations or polymorphisms in precore region were more common among genotype D compared to genotype A isolates. The HBV genotypic distribution in this Caribbean island correlates with the Y lineage genetic background of the population, where a European and African origin prevails. HBV genotypes E, B3 and H isolates might represent more recent introductions. PMID:25742179

  5. The HBV Drugs Work: Now What?

    PubMed

    Pruett, Timothy L

    2016-09-01

    Chemotherapeutic agents for Hepatitis B virus (HBV) suppression work, but only when administered to the patient. They do not appear to promote durable, long-term immunological control. After 3 years of effective anti-HBV therapy, a small percentage of patients maintained good control, manifest by controlled serum liver enzymes, low-level HBV-DNA, and controlled HBsAg concentrations. However, this did not occur in the majority of patients. We need a better understanding of the defects in HBV immunity and how to induce effective reconstitution that will maintain viral suppression, albeit either through innate or adaptive immunity. PMID:27580778

  6. Inhibition of hepatitis B virus (HBV) by LNA-mediated nuclear interference with HBV DNA transcription

    SciTech Connect

    Sun, Zhen; Xiang, Wenqing; Guo, Yajuan; Chen, Zhi; Liu, Wei; Lu, Daru

    2011-06-10

    Highlights: {yields} LNA-modified oligonucleotides can pass through the plasma membrane of cultured cells even without using transfection machinery. {yields} LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. {yields} LNA-oligonucleotide designed to target nuclear HBV DNA efficiently suppresses HBV replication and transcription in cultured hepatic cells. -- Abstract: Silencing target genes with small regulatory RNAs is widely used to investigate gene function and therapeutic drug development. Recently, triplex-based approaches have provided another attractive means to achieve targeted gene regulation and gene manipulation at the molecular and cellular levels. Nuclear entry of oligonucleotides and enhancement of their affinity to the DNA targets are key points of such approaches. In this study, we developed lipid-based transport of a locked-nucleic-acid (LNA)-modified oligonucleotide for hepatitis B virus (HBV) DNA interference in human hepatocytes expressing HBV genomic DNA. In these cells, the LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. The oligonucleotide specifically targeting HBV DNA clearly interfered with HBV DNA transcription as shown by a block in pregenomic RNA (pgRNA) production. The HBV DNA-targeted oligonucleotide suppressed HBV DNA replication and HBV protein production more efficiently than small interfering RNAs directed to the pgRNA. These results demonstrate that fusion with lipid can carry LNA-modified oligonucleotides to the nucleus where they regulate gene expression. Interfering with HBV DNA transcription by LNA-modified oligonucleotides has strong potential as a new strategy for HBV inhibition.

  7. A mouse model for HBV immunotolerance and immunotherapy.

    PubMed

    Yang, Dan; Liu, Longchao; Zhu, Danming; Peng, Hua; Su, Lishan; Fu, Yang-Xin; Zhang, Liguo

    2014-01-01

    Lack of an appropriate small animal model remains a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B virus (HBV) infection. In this study, we report a mouse model with sustained HBV viremia after infection with a recombinant adeno-associated virus (AAV) carrying a replicable HBV genome (AAV/HBV). Similar to the clinical HBV carriers, the mice infected with AAV/HBV were sero-negative for antibodies against HBV surface antigen (HBsAg). Immunization with the conventional HBV vaccine in the presence of aluminum adjuvant failed to elicit an immune response against HBV in these mice. To identify a vaccine that can potentially circumvent this tolerance, the TLR9 agonist CpG was added to HBsAg as an adjuvant. Vaccination of mice with HBsAg/CpG induced not only clearance of viremia, but also strong antibody production and T-cell responses. Furthermore, both the DNA replication and protein expression of HBV were significantly reduced in the livers of AAV/HBV-infected mice. Accordingly, AAV/HBV-infected mice may be used as a robust model for investigating the underlying mechanism(s) of HBV immunotolerance and for developing novel immunotherapies to eradicate HBV infections. PMID:24076617

  8. Global strategies are required to cure and eliminate HBV infection.

    PubMed

    Revill, Peter; Testoni, Barbara; Locarnini, Stephen; Zoulim, Fabien

    2016-04-01

    Chronic HBV infection results in >1 million deaths per year from cirrhosis and liver cancer. No known cure for chronic HBV exists, due in part to the continued presence of transcriptionally active DNA in the nucleus that is not directly targeted by current antiviral therapies. A coordinated approach is urgently needed to advance an HBV cure worldwide, such as those established in the HIV field. We propose the establishment of an International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) to facilitate the formation of international working groups on HBV virology, immunology, innovative tools and clinical trials: to promote awareness and education as well as to drive changes in government policy and ensure funds are channelled to HBV cure research and drug development. With the ICE-HBV in place, it should be possible to enable a HBV cure within the next decade. PMID:26907881

  9. The Role of Immune Cells in Chronic HBV Infection

    PubMed Central

    Li, Hai-Jun; Zhai, Nai-Cui; Song, Hong-Xiao; Yang, Yang; Cui, An; Li, Tian-Yang; Tu, Zheng-Kun

    2015-01-01

    Hepatitis B virus (HBV) infection is a major cause of chronic liver diseases that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses are important factors that determine whether HBV infection is cleared or persists. After infection, viral replication occurs inside hepatocytes, and the secretion of infectious virions can take place at high rates for decades. Consequently, HBV DNA and viral proteins, like HBV early antigen (HBeAg) and HBV surface antigen (HBsAg), can be easily detected in serum. Chronic infection with HBV is the result of an ineffective antiviral immune response towards the virus. In this review, we discuss the role of immune cells in chronic HBV infection. PMID:26807384

  10. [Extrahepatic manifestations of HBV and HCV infection].

    PubMed

    Hartmann, H

    1997-07-16

    Acute as well as chronic infections by HBV and HCV can be associated with extrahepatic disease. As in liver disease of non-viral etiology, several extrahepatic manifestations can be observed that are non-specific for HBV or HCV, e.g. those clinical signs and symptoms frequently encountered when cirrhosis of the liver is present. In addition, distinct clinical conditions have been described in which the unterlying liver disease is specifically due to HBV or HCV infection. In chronic HBV infection, glomerulonephritis (of the membranous and of the membranoproliferative type) and polyarteritis nodosa have been observed. The pathogenesis of both conditions involves the deposition of circulating immune complexes. Although controlled trials are lacking, interferon therapy appears to be beneficial. The use of immunosuppressive drugs and of plasmapheresis should probably be limited to the initial phase of treatment. In chronic HCV infection, mixed cryoglobulinemia (and ensuing systemic vasculitis) is a frequent extrahepatic manifestation. The clinical presentation might include the presence of purpura, arthralgias, weakness and renal involvement. Nowadays, HCV can be regarded as the etiological agent of a form of mixed cryoglobulinemia formerly considered to be 'essential'. In addition, an association to lymphoma has been postulated recently. Interferon alpha has been used for treatment with similar response rates as those observed in HCV-infected patients without cryoglobulinemia. Interestingly, the antiviral activity of interferon, e.g. normalization of transaminases and loss of serum HCV RNA, was closely related to the beneficial effect on cryoglobulinemia. An association of Sjögren's syndrome and of porphyria cutanea tarda to HCV infection (though claimed before) remains questionable. Serological markers of autoimmunity, e.g. antinuclear antibodies or anti-LKM-1, are present in many patients with chronic HCV infection. The clinical relevance of this latter observation

  11. HBV endemicity in Mexico is associated with HBV genotypes H and G

    PubMed Central

    Roman, Sonia; Panduro, Arturo

    2013-01-01

    Hepatitis B virus (HBV) genotypes have distinct genetic and geographic diversity and may be associated with specific clinical characteristics, progression, severity of disease and antiviral response. Herein, we provide an updated overview of the endemicity of HBV genotypes H and G in Mexico. HBV genotype H is predominant among the Mexican population, but not in Central America. Its geographic distribution is related to a typical endemicity among the Mexicans which is characterized by a low hepatitis B surface antigen seroprevalence, apparently due to a rapid resolution of the infection, low viral loads and a high prevalence of occult B infection. During chronic infections, genotype H is detected in mixtures with other HBV genotypes and associated with other co-morbidities, such as obesity, alcoholism and co-infection with hepatitis C virus or human immunodeficiency virus. Hepatocellular carcinoma prevalence is low. Thus, antiviral therapy may differ significantly from the standard guidelines established worldwide. The high prevalence of HBV genotype G in the Americas, especially among the Mexican population, raises new questions regarding its geographic origin that will require further investigation. PMID:24023487

  12. Clinical Relevance of HLA Gene Variants in HBV Infection

    PubMed Central

    Wang, Li; Zou, Zhi-Qiang; Wang, Kai

    2016-01-01

    Host gene variants may influence the natural history of hepatitis B virus (HBV) infection. The human leukocyte antigen (HLA) system, the major histocompatibility complex (MHC) in humans, is one of the most important host factors that are correlated with the clinical course of HBV infection. Genome-wide association studies (GWASs) have shown that single nucleotide polymorphisms (SNPs) near certain HLA gene loci are strongly associated with not only persistent HBV infection but also spontaneous HBV clearance and seroconversion, disease progression, and the development of liver cirrhosis and HBV-related hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB). These variations also influence the efficacy of interferon (IFN) and nucleot(s)ide analogue (NA) treatment and response to HBV vaccines. Meanwhile, discrepant conclusions were reached with different patient cohorts. It is therefore essential to identify the associations of specific HLA allele variants with disease progression and viral clearance in chronic HBV infection among different ethnic populations. A better understanding of HLA polymorphism relevance in HBV infection outcome would enable us to elucidate the roles of HLA SNPs in the pathogenesis and clearance of HBV in different areas and ethnic groups, to improve strategies for the prevention and treatment of chronic HBV infection. PMID:27243039

  13. Progress and Prospects of Anti-HBV Gene Therapy Development

    PubMed Central

    Maepa, Mohube B.; Roelofse, Ilke; Ely, Abdullah; Arbuthnot, Patrick

    2015-01-01

    Despite the availability of an effective vaccine against hepatitis B virus (HBV), chronic infection with the virus remains a major global health concern. Current drugs against HBV infection are limited by emergence of resistance and rarely achieve complete viral clearance. This has prompted vigorous research on developing better drugs against chronic HBV infection. Advances in understanding the life cycle of HBV and improvements in gene-disabling technologies have been impressive. This has led to development of better HBV infection models and discovery of new drug candidates. Ideally, a regimen against chronic HBV infection should completely eliminate all viral replicative intermediates, especially covalently closed circular DNA (cccDNA). For the past few decades, nucleic acid-based therapy has emerged as an attractive alternative that may result in complete clearance of HBV in infected patients. Several genetic anti-HBV strategies have been developed. The most studied approaches include the use of antisense oligonucleotides, ribozymes, RNA interference effectors and gene editing tools. This review will summarize recent developments and progress made in the use of gene therapy against HBV. PMID:26263978

  14. Genie Pro

    Energy Science and Technology Software Center (ESTSC)

    2004-05-15

    Genie Pro is a general purpose, interactive, adaptive tool for automatically labeling regions and finding objects in large amounts of image data. Genie Pro uses supervised learning techniques to search for spatio-spectral algorithms that are best able to match exaple labels provided by a user during a training session. After Genie Pro has discovered a useful algorithm, this algorith can then be applied to other similar types of image data, to label regions and objectsmore » similar to those provided during the training session. Genie Pro was originally developed for analyzing multispectral satellite data, but it works equally well with panchromatic (grayscale) and hyperspectral satellite data, aerial imagery, and various kinds of medical imagery. AS a rough guideline, Genie Pro can work with any imagery where the scene being imaged is all approximately at a constant distance fromt he imaging device, and so the scale of imagery is fixed. Applications for Genie Pro include: Crop and terrain type mapping, Road and river network mapping, Broad area search for vehicles and buildings, and Cancer identification in histological images.« less

  15. Bloodborne Pathogens: HIV and HBV Contagion Risks at Camp.

    ERIC Educational Resources Information Center

    Skaros, Susan

    1996-01-01

    AIDS and hepatitis B are diseases caused by the viruses HIV and HBV, respectively, which are spread in blood and body fluids. HBV is 100 times more contagious than HIV. Diligent implementation of universal precautions, an exposure control plan, use of personal protective equipment, a vaccination program, and ongoing staff and camper education can…

  16. If You Have Chronic Hepatitis B Virus (HBV) Infection

    MedlinePlus

    If you have chronic hepatitis B virus (HBV) infection . . . If you have chronic hepatitis B virus (HBV) infection, you are not alone. Today, approximately one ... receive pneumococcal polysaccharide vac- cine.  Get vaccinated against hepatitis A. Hepati- tis A can further damage your ...

  17. HBV vaccine efficacy and detection and genotyping of vaccineé asymptomatic breakthrough HBV infection in Egypt

    PubMed Central

    Abushady, Eman AE; Gameel, Magda MA; Klena, John D; Ahmed, Salwa F; Abdel-Wahab, Kouka SE; Fahmy, Sanya M

    2011-01-01

    AIM: To evaluate the impact of mass vaccination against the hepatitis B virus (HBV) in Egypt, and to search for vaccinee asymptomatic breakthrough HBV infection and its genotype. METHODS: Seven hundred serum samples from vaccinated children and adults (aged 2-47 years) were used for quantitative and qualitative detection of HBsAb by ELISA. Three hundred and sixty serum samples representing undetectable or low or high HBsAb were screened for markers of active HBV infection (HBsAg, HBcAb (IgG) and HBeAb by ELISA, plus HBsAg by AxSYM) and HBV-DNA genotyping by nested multiplex PCR and by DNA sequencing. RESULTS: It was found that 65% of children aged 2-4 years, and 20.5% aged 4-13 years, as well as 45% adults were good responders to HBV vaccination mounting protective level HBsAb. Poor responders were 28%, 59.5% and 34%, and non-responders were 7%, 20% and 21% respectively, in the three studied groups. Markers of asymptomatic HBV infections were HBsAg detected by ELISA in 2.5% vs 11.39% by AxSYM. Other markers were HBcAb (IgG) in 1.38%, HBeAb in 0.83%, and HBV-DNA in 7.8%. All had HBV genotype E infection. CONCLUSION: It is concluded that HBV vaccine is efficient in controlling HBV infection among children and adults. The vaccine breakthrough infection was by HBV genotype E. A booster dose of vaccine is recommended, probably four years after initial vaccination. PMID:21860674

  18. Application of CRISPR/Cas9 Technology to HBV

    PubMed Central

    Lin, Guigao; Zhang, Kuo; Li, Jinming

    2015-01-01

    More than 240 million people around the world are chronically infected with hepatitis B virus (HBV). Nucleos(t)ide analogs and interferon are the only two families of drugs to treat HBV currently. However, none of these anti-virals directly target the stable nuclear covalently closed circular DNA (cccDNA), which acts as a transcription template for viral mRNA and pre-genomic RNA synthesis and secures virus persistence. Thus, the fact that only a small number of patients treated achieve sustained viral response (SVR) or cure, highlights the need for new therapies against HBV. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing system can specifically target the conserved regions of the HBV genome. This results in robust viral suppression and provides a promising tool for eradicating the virus. In this review, we discuss the function and application of the CRISPR/Cas9 system as a novel therapy for HBV. PMID:26540039

  19. Rapamycin Enhances HBV Production by Inducing Cellular Autophagy

    PubMed Central

    Huang, Wenjuan; Zhao, Fengrong; Huang, Ying; Li, Xia; Zhu, Sufei; Hu, Qin; Chen, Weixian

    2014-01-01

    Background: Some reports revealed that rapamycin could reactivate HBV infection. However, the mechanism has not been clearly explained. Objectives: In this report, we studied the mechanism by which rapamycin enhances HBV replication and expression by inducing cellular autophagy. Materials and Methods: HepG2.2.15 cells were treated with rapamycin to induce autophagy. Autophagosomes were observed by fluorescence microscopy and transmission electron microscopy. Autophagy marker protein LC3-Ⅱ/LC3-Ⅰwas detected by Western blotting. HBV DNA and mRNA were determined by real time PCR and Southern blotting. HBsAg was evaluated by ELISA. Results: In HepG2.2.15 cells, HBV DNA and HBsAg increased when host cells were treated with rapamycin and the effect was reversed by autophagy inhibitor, 3-methyladenine (3-MA). Conclusions: These results indicated a potential explanation for reactivation of HBV infection when patients with hepatitis receive rapamycin. PMID:25419217

  20. Epigallocatechin-3-gallate opposes HBV-induced incomplete autophagy by enhancing lysosomal acidification, which is unfavorable for HBV replication

    PubMed Central

    Zhong, L; Hu, J; Shu, W; Gao, B; Xiong, S

    2015-01-01

    Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, exhibits diverse beneficial properties, including antiviral activity. Autophagy is a cellular process that is involved in the degradation of long-lived proteins and damaged organelles. Recent evidence indicates that modulation of autophagy is a potential therapeutic strategy for various viral diseases. In the present study, we investigated the effect of EGCG on hepatitis B virus (HBV) replication and the possible involvement of autophagy in this process. Our results showed that HBV induced autophagosome formation, which was required for replication of itself. However, although EGCG efficiently inhibited HBV replication, it enhanced, but not inhibited, autophagosome formation in hepatoma cells. Further study showed that HBV induced an incomplete autophagy, while EGCG, similar to starvation, was able to induce a complete autophagic process, which appeared to be unfavorable for HBV replication. Furthermore, it was found that HBV induced an incomplete autophagy by impairing lysosomal acidification, while it lost this ability in the presence of EGCG. Taken together, these data demonstrated that EGCG treatment opposed HBV-induced incomplete autophagy via enhancing lysosomal acidification, which was unfavorable for HBV replication. PMID:25996297

  1. Therapeutic vaccines in HBV: lessons from HCV.

    PubMed

    Barnes, Eleanor

    2015-02-01

    Currently, millions of people infected with hepatitis B virus (HBV) are committed to decades of treatment with anti-viral therapy to control viral replication. However, new tools for immunotherapy that include both viral vectors and molecular checkpoint inhibitors are now available. This has led to a resurgence of interest in new strategies to develop immunotherapeutic strategies with the aim of inducing HBeAg seroconversion--an end-point that has been associated with a decrease in the rates of disease progression. Ultimately, a true cure will involve the elimination of covalently closed circular DNA which presents a greater challenge for immunotherapy. In this manuscript, I describe the development of immunotherapeutic strategies for HBV that are approaching or currently in clinical studies, and draw on observations of T cell function in natural infection supported by recent animal studies that may lead to additional rational vaccine strategies using checkpoint inhibitors. I also draw on our recent experience in developing potent vaccines for HCV prophylaxis based on simian adenoviral and MVA vectors used in prime-boost strategies in both healthy volunteers and HCV infected patients. I have shown that the induction of T cell immune responses is markedly attenuated when administered to people with persistent HCV viremia. These studies and recently published animal studies using the woodchuck model suggest that potent vaccines based on DNA or adenoviral vectored vaccination represent a rational way forward. However, combining these with drugs to suppress viral replication, alongside checkpoint inhibitors may be required to induce long-term immune control. PMID:25573348

  2. Breastfeeding and chronic HBV infection: Clinical and social implications

    PubMed Central

    Petrova, Mihaela; Kamburov, Victor

    2010-01-01

    Mother-to-child transmission of hepatitis B virus (HBV) is among the most important causes of chronic HBV infection and is the commonest mode of transmission worldwide. Currently, the presence of HBsAg, HBeAg and HBV DNA in breast milk is confirmed. Several studies have reported that breastfeeding carries no additional risk that might lead to vertical transmission. Beyond some limitations, the surveys have not demonstrated any differences in HBV transmission rate regarding feeding practices in early childhood. Promotion of breastfeeding is substantial, especially for low-income individuals and regions with uncertain, unfeasible, and unsafe water supplies. Lactoferrin, minimal inflammation or activation within the infant gut during exclusive breastfeeding, and nonspecific biological molecules in the milk are identified as major factors of breast-milk defense. This review discusses preemptive antiviral therapy during pregnancy and lactation. Long-term follow up of breast-milk HBV concentrations and correlation with serum viral load; nucleos(t)ide analogue concentrations in breast milk in HBV-positive mothers in the setting of chronic HBV infection; safety of antiviral therapy during pregnancy and lactation; and the difference in viral load in the milk in exclusive or non-exclusive breastfeeding are still open questions. The paper reviews the current data and outlines the course of further investigation into this often underestimated issue. PMID:20976840

  3. HBV DNA vaccine with adjuvant cytokines induced specific immune responses against HBV infection

    PubMed Central

    Du, De-Wei; Jia, Zhan-Sheng; Li, Guang-Yu; Zhou, Yong-Ying

    2003-01-01

    AIM: To seek for an effective method to improve the immune responses induced by DNA vaccine expressing HBV surface antigen (pCR3.1-S) in Balb/c mice (H-2d). METHODS: The pCR3.1-S plasmid and the eukaryotic expression vectors expressing murine IL-2 (pDOR-IL-2) or IL-12 (pWRG3169) were injected into mice subcutaneously. The immune responses to pCR3.1-S and the adjuvant effect of the cytokines plasmid were studied. Meanwhile the effect of pCR3.1-S on anti-translated subcutaneous tumor of P815 mastocytoma cells stably expressing HBsAg (P815-HBV-S) was also studied. Anti-HBs in serum was detected by enzyme-linked immunoadsordent assay (ELISA) and HBsAg specific cytotoxic T lymphocytes (CTLs) activity was measured by 51Cr release assay. After three weeks of DNA immunization, the cells of P815-HBV-S were inoculated into mice subcutaneously and the tumor growth was measured every five days. The survival rate and living periods of mice were also calculated. RESULTS: After 8 wk DNA immunization, the A 450 nm values of sera in mice immunized with pCR3.1, pCR3.1-S and pCR3.1-S codeliveried with IL-2 or IL-12 plasmids were 0.03 ± 0.01, 1.24 ± 0.10, 1.98 ± 0.17 and 1.67 ± 0.12 respectively. Data in mice codeliveried pCR3.1-S with IL-2 or IL-12 plasmids were significantly higher than that of mice injected pCR3.1 or pCR3.1-S only. The HBsAg specific CTL activities in mice coinjected with pCR3.1-S and IL-2 or IL-12 eukaryotic expression vectors were (61.9 ± 7.1)% and (73.3 ± 8.8)%, which were significantly higher than that of mice injected with pCR3.1 (10.1 ± 2.1)% or pCR3.1-S (50.5 ± 6.4)%. The HBsAg specific CTL activities in mice injected with pCR3.1, pCR3.1-S, pCR3.1-S combined with IL-2 or IL-12 eukaryotic expression vectors decreased significantly to (3.2 ± 0.8)%, (10.6 ± 1.4)%, (13.6 ± 1.3)% and (16.9 ± 2.3)% respectively after the spleen cells were treated by anti-CD8+ monoclonal antibody, but presented no significant change to anti-CD4+ monoclonal antibody or

  4. Trained immunity in newborn infants of HBV-infected mothers

    PubMed Central

    Hong, Michelle; Sandalova, Elena; Low, Diana; Gehring, Adam J.; Fieni, Stefania; Amadei, Barbara; Urbani, Simonetta; Chong, Yap-Seng; Guccione, Ernesto; Bertoletti, Antonio

    2015-01-01

    The newborn immune system is characterized by an impaired Th1-associated immune response. Hepatitis B virus (HBV) transmitted from infected mothers to newborns is thought to exploit the newborns’ immune system immaturity by inducing a state of immune tolerance that facilitates HBV persistence. Contrary to this hypothesis, we demonstrate here that HBV exposure in utero triggers a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhances the ability of cord blood immune cells to respond to bacterial infection in vitro. These training effects are associated with an alteration of the cytokine environment characterized by low IL-10 and, in most cases, high IL-12p40 and IFN-α2. Our data uncover a potentially symbiotic relationship between HBV and its natural host, and highlight the plasticity of the fetal immune system following viral exposure in utero. PMID:25807344

  5. Changes of HBV DNA After Chemoembolization for Hepatocellular Carcinoma and the Efficacy of Antiviral Treatment.

    PubMed

    Lin, Xiao-Jun; Lao, Xiang-Ming; Shi, Ming; Li, Sheng-Ping

    2016-09-01

    Unlike systemic chemotherapy for hematological malignancies with hepatitis B virus (HBV) infection, transarterial chemoembolization (TACE) for HBV-related hepatocellular carcinoma (HCC) has only recently been reported to cause HBV reactivation and subsequent hepatitis. Most patients with HBV-related HCC have an underlying disease with liver fibrosis or cirrhosis, and TACE may potentially induce HBV reactivation and liver decompensation. Currently, there are no clinical guidelines for managing TACE-caused HBV reactivation. In this review, we summarize the changes of HBV status and liver function after TACE and the effect of antiviral treatment before, during, or after TACE. PMID:27105647

  6. Polymorphisms of FGFR1 in HBV-related hepatocellular carcinoma.

    PubMed

    Xie, Haiyang; Xing, Chunyang; Wei, Bajin; Xu, Xiao; Wu, Liming; Wu, Jian; Chen, Leiming; Cao, Guoqiang; Chen, Hai; Meng, Xueqin; Yin, Shengyong; Zhou, Lin; Zheng, Shusen

    2015-11-01

    Hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers in China. It is important to understand the genetic mechanisms underlying the development and progression of HBV-related HCC and to identify new biomarkers for clinical treatment. The important role of fibroblast growth factor receptors (FGFRs) has been widely recognized in many types of cancers, but the association between FGFR polymorphisms and HCC carcinogenesis has been rarely reported. In this study, 199 patients with HBV-associated cirrhosis, 203 with HBV-associated HCC, and 184 healthy controls with no liver diseases were enrolled as participants. Using SNaPshot assays, five SNPs (rs13317, rs7825208, rs1047057, rs1047111, and rs1966265) of growth factor receptor genes were genotyped. Our results showed that the G/A and G/G genotypes at rs7825208 of FGFR1 were negatively correlated with HBV-related HCC (odds ratio (OR) = 0.45, 95% confidence interval (CI) = 0.22-0.93, P = 0.027). However, after Bonferroni correction, these significant differences no longer existed (P > 0.05). Our results indicated that these five polymorphisms of fibroblast growth factor receptor genes do not play any independent roles in the tumorigenesis and progression of HBV-related HCC in Han Chinese patients. PMID:26069105

  7. TLR3 Plays Significant Roles against HBV-Associated HCC

    PubMed Central

    Chen, Xiao-lan; Xu, Yu-yin; Chen, Li; Wang, Gui-lan; Shen, Yin

    2015-01-01

    Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in immune signaling and plays a crucial role in survival by being able to recognize various viral components including double-stranded RNA (dsRNA). The role of TLR3 in hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infections is not well understood. To investigate the ability of TLR3 in regulating HBV replication in HCC, 80 cases of human HCC were collected and their tissue microarray was made. In HCC cells, the expression and location of TLR3, hepatitis-associated virus, and interstitial immunoreactive cells were assayed with immunohistochemical staining. The apoptosis of tumor cells was also detected by TUNEL stain. Correlations between TLR3 expression and HBV infection, interstitial immunoreactive cells, and cells apoptosis in HCC were investigated. In addition, we explored whether TLR3 agonist dsRNA can inhibit HepG2.2.15 cells secreting HBV. We found that the cytoplasmic expression of TLR3 in HCC is positively related to HBsAg infection and HCC with cirrhosis and promotes interstitial immunoreactive cells infiltration and cancer cells apoptosis. In HepG2.2.15 cells, dsRNA inhibited the secretion of HBV and induced apoptosis. These results indicate that TLR3 signaling activity may be involved in immune responses against HBV in HCC. PMID:25983748

  8. HBV-Associated Postinfectious Acute Glomerulonephritis: A Report of 10 Cases

    PubMed Central

    Zhang, Yong; Li, Junxia; Peng, Weihua; Yu, Guoqing; Wang, Liping; Chen, Jian; Zheng, Feng

    2016-01-01

    Postinfectious acute glomerulonephritis (PIGN) may occur after various bacterial and viral infections. Hepatitis B virus (HBV) infection is a cause of chronic glomerulonephritis. We report here 10 cases (ages 7–20 years-old) of chronic HBV carriers with acute glomerulonephritis, with positive glomerular staining of hepatitis B surface antigen, and detectable presence of HBV DNA in the glomeruli. This form of PIGN, HBV-PIGN, has not been previously identified. To further characterize clinical and pathological features of HBV- PIGN, we selected 10 cases of age-matched non-HBV PIGN for comparison. While both HBV associated PIGN and non-HBV PIGN similarly presented as proteinuria, hematuria, and hypertension, there was a trend of higher acute kidney injury and worsened prognosis in HBV-PIGN. 6 months after the onset, 4 patients with HBV associated PIGN did not show improvement from the disease, whereas all patients with non-HBV PIGN had complete or partial recovery. Pathologically, both HBV associated PIGN and non-HBV PIGN showed typical diffuse glomerular endocapillary proliferation, but HBV associated PIGN differed from classical PIGN with much fewer sub-epithelial glomerular “hump-shape” immune complex depositions. In conclusion, we have identified a novel association of HBV infection with acute glomerulonephritis. PMID:27512989

  9. A Novel Hydrodynamic Injection Mouse Model of HBV Genotype C for the Study of HBV Biology and the Anti-Viral Activity of Lamivudine

    PubMed Central

    Li, Xiumei; Liu, Guangze; Chen, Meijuan; Yang, Yang; Xie, Yong; Kong, Xiangping

    2016-01-01

    Background: Absence of an immunocompetent mouse model of persistent hepatitis B virus (HBV) infection has hindered the research of HBV infection and the development of antiviral medications. Objectives: In the present study, we aimed to develop a novel HBV genotype C mouse model by hydrodynamic injection (HI) and then used it to evaluate the antiviral activity of lamivudine. Materials and Methods: A quantity of 15 μg of HBV plasmid [pcDNA3.1 (+)-HBV1.3C], adeno-associated virus-HBV1.3C (pAAV-HBV1.3C) or pAAV-HBV1.2A) were injected into male C57BL/6 mice, by HI, accounting for a total of 13 mice per group. Then, lamivudine was administered to mice with sustained HBV viremia, for 4 weeks. Real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry methods were used to detect HBsAg, HBeAg, HBsAb, HBcAg and HBV DNA, in serum or liver of the mice, at indicated time points. Results: In 60% of the mice injected with pcDNA3.1 (+)-HBV1.3C, HBsAg, HBeAg, HBcAg and HBV DNA persisted for > 20 weeks in liver, post-injection, with no HBsAb appearance. Meanwhile, no significant inflammation was observed in these mice. Compared with pAAV-HBV1.2A and pAAV-HBV1.3C, pcDNA3.1 (+)-HBV1.3C administration led to higher and longer HBV viremia. Furthermore, serum HBV DNA was significantly reduced by lamivudine, after 4 weeks administration, and returned to the original level, after ceasing administration for 1 week, in the mice. Conclusions: In conclusion, our observations indicated that pcDNA3.1 (+)-HBV1.3C was superior to AAV/HBV plasmid for establishment of persistent HBV infection by HI, in vivo, and this mouse model could be useful for studies of hepatitis virology and for the development of innovatory treatments for HBV infections. PMID:27195013

  10. The prognosis and management of inactive HBV carriers.

    PubMed

    Invernizzi, Federica; Viganò, Mauro; Grossi, Glenda; Lampertico, Pietro

    2016-01-01

    Patients with chronic hepatitis B virus (HBV) infection lacking the serum hepatitis B e antigen (HBeAg) and with antibodies against HBeAg (anti-HBe), are the prevalent subgroup of HBV carriers worldwide. The prognosis of these patients is different from inactive carriers (ICs), who are characterized by persistently normal serum alanine aminotransferase (ALT) and low (<2000 IU/ml) serum HBV DNA levels, a serological profile that may also be intermittently observed in patients with HBeAg-negative chronic hepatitis. This is why a confirmed diagnosis of IC requires quarterly ALT and HBV DNA measurements for at least 1 year, while a single-point detection of combined HBsAg <1000 IU/ml and HBV DNA <2000 IU/ml has a robust predictive value for the diagnosis of IC. Characteristically, ICs have minimal or no histological lesions of the liver corresponding to liver stiffness values on Fibroscan of <5 kPa. Antiviral treatment is not indicated in ICs since the prognosis for the progression of liver disease is favourable if there are no cofactors of liver damage such as alcohol abuse, excess weight or co-infection with the hepatitis C virus or delta virus. Moreover, spontaneous HBsAg loss frequently occurs (1-1.9% per year) in these patients while the development of hepatocellular carcinoma (HCC) is rare, at least in Caucasian patients. However, an emerging issue reinforcing the need for clinical surveillance of ICs is the risk of HBV reactivation in patients who undergo immunosuppressive therapy without receiving appropriate antiviral prophylaxis. After diagnosis, management of ICs includes monitoring of ALT and HBV DNA every 12 months with periodic measurement of serum HBsAg levels to identify viral clearance. PMID:26725905

  11. [Establishment of hepatitis B virus (HBV) chronic infection mouse model by in vivo transduction with a recombinant adeno-associated virus 8 carrying 1. 3 copies of HBV genome (rAAN8-1. 3HBV)].

    PubMed

    Dong, Xiao-Yan; Yu, Chi-Jie; Wang, Gang; Tian, Wen-Hong; Lu, Yue; Zhang, Feng-Wei; Wang, Wen; Wang, Yue; Tan, Wen-Jie; Wu, Xiao-Bing

    2010-11-01

    In this report, we developed a HBV infection model in C57BL/6 mouse line by in vivo injection of a recombinant adeno-associated virus 8 vector carrying 1. 3 copies of HBV genome (ayw subtype) (rAAV8-1. 3HBV). We firstly prepared and purified the rAAV8-1. 3HBV and then injected it into three C57BL/6 mice with the dose of 2 x 10e11vg, respectively. HBsAg and HBeAg were assayed in sera collected at different time points post injection. Ten weeks post injection, the three mice were sacrificed and blood and liver tissue were taken for assay. Copies of HBV DNA were detected by real time PCR and the way of HBV DNA replication was identified by PCR. Subsequently, detection of HBV antigen by immunohistochemistry and pathology analysis of liver tissue of mice were performed. The results suggested that expression of HBsAg and HBeAg lasted for at least 10 weeks in mice sera. Among mice injected with rAAV8-1. 3HBV, HBsAg levels were showed an 'increasing-decreasing-increasing' pattern (the lowest level at the 4th week post injection), while HBeAg levels were kept high and relatively stable. HBV DNA copies were 4.2 x 10(3), 3.6 x 10(3), 2.5 x 10(3) copies/mL in sera and 8.0 x 10(6), 5.7 x 10(6), 2.6 x 10(6) copies/g in hepatic tissues of three mice, respectively. We found that the linear 1. 3HBV DNA in the rAAV8-1. 3HBV could self form into circular HBV genome and replicate in livers of HBV transfected mice. HBsAg and HBcAg were both positive in liver tissue of mice injected with rAAV8-1. 3HBV and no obvious pathological characters were found in liver of mice injected with rAAV8-1. 3HBV. In conclusion, we successfully developed a HBV chronic infection model in C57BL/6 mouse line by in vivo transduction with the recombinant virus rAAV8-1. 3HBV, in which HBV genes could be continuously expressed and replicated over 10 weeks, and paved a way for further characterization of the human chronic hepatitis B virus infection and evaluation of vaccine and anti-HBV agents. PMID:21344744

  12. Differences in antiproliferative effect of STAT3 inhibition in HCC cells with versus without HBV expression

    SciTech Connect

    Hong, Yun; Zhou, Lin; Xie, Haiyang; Wang, Weilin; Zheng, Shusen

    2015-06-05

    Chronic infection with hepatitis B virus (HBV) plays an important role in the etiology of hepatocellular carcinoma (HCC). Signal transducer and activator of transcription 3 (STAT3) inactivation could inhibit the tumor growth of HCC. In this study, differential antiproliferative effect of STAT3 inhibition was observed with HBV-related HCC cells being more resistant than non-HBV-related HCC cells. Resistance of HBV-related HCC cells to STAT3 inhibition was positively correlated to the expression of HBV. Enhanced ERK activation after STAT3 blockade was detected in HBV-related HCC cells but not in non-HBV-related HCC cells. Combined ERK and STAT3 inhibition eliminates the discrepancy between the two types of HCC cells. Moderate reduced HBV expression was found after STAT3 inhibition. These findings disclose a discrepancy in cellular response to STAT3 inhibition between non-HBV-related and HBV-related HCC cells and underscore the complexity of antiproliferative effect of STAT3 inactivation in HBV-related HCC cells. - Highlights: • HBV endows HCC cells with resistance to STAT3 inactivation on proliferation. • Abnormal ERK activation after STAT3 inhibition in HBV-related HCC cells. • Combined ERK and STAT3 inhibition eliminates the discrepancy. • STAT3 inhibition moderately reduces HBV expression.

  13. Virologic and Clinical Outcomes of Hepatitis B Virus Infection in HIV-HBV Coinfected Transplant Recipients

    PubMed Central

    Coffin, C.S.; Stock, P.G.; Dove, L.M.; Berg, C.L.; Nissen, N.N.; Curry, M.P.; Ragni, M.; Regenstein, F.G.; Sherman, K.E.; Roland, M.E.; Terrault, N.A.

    2010-01-01

    Liver transplantation (LT) is the treatment of choice for endstage liver disease, but is controversial in patients with human immunodeficiency virus (HIV) infection. Using a prospective cohort of HIV-HBV coinfected patients transplanted between 2001–2007; outcomes including survival and HBV clinical recurrence were determined. Twenty-two coinfected patients underwent LT; 45% had detectable HBV DNA pre-LT and 72% were receiving anti-HBV drugs with efficacy against lamivudine-resistant HBV. Post-LT, all patients received hepatitis B immune globulin (HBIG) plus nucleos(t)ide analogues and remained HBsAg negative without clinical evidence of HBV recurrence, with a median follow-up 3.5 years. Low-level HBV viremia (median 108 IU/ml, range 9–789) was intermittently detected in 7/13 but not associated with HBsAg detection or ALT elevation. Compared with 20 HBV monoinfected patients on similar HBV prophylaxis and median follow-up of 4.0 years, patient and graft survival were similar: 100% vs. 85% in HBV mono- vs coinfected patients (p=0.08, log rank test). LT is effective for HIV-HBV coinfected patients with complications of cirrhosis, including those who are HBV DNA positive at the time of LT. Combination HBIG and antivirals is effective as prophylaxis with no clinical evidence of HBV recurrence but low level HBV DNA is detectable in ~50% of recipients. PMID:20346065

  14. Reliable timescale inference of HBV genotype A origin and phylodynamics.

    PubMed

    Zehender, Gianguglielmo; Svicher, Valentina; Gabanelli, Elena; Ebranati, Erika; Veo, Carla; Lo Presti, Alessandra; Cella, Eleonora; Giovanetti, Marta; Bussini, Linda; Salpini, Romina; Alteri, Claudia; Lai, Alessia; Tanzi, Elisabetta; Perno, Carlo Federico; Galli, Massimo; Ciccozzi, Massimo

    2015-06-01

    The worldwide distributed Hepatitis B virus (HBV) genotype A is classified into three subgenotypes, and one quasi-subgenotype. The majority of HBV-A subgenotypes are widespread in Africa and in ethnic groups that have relatively recently emigrated from African countries, whereas HBV-A2 is highly prevalent among subjects at high risk for sexual exposure to HBV in north-western Europe and the USA. The aim of this study was to reconstruct the origin and dispersion of HBV-A subgenotypes on a reliable timescale using short-term calibration based on heterochronous sampling for HBV-A2, and long-term calibration based on historical data for the other subgenotypes. To this aim, we analysed 113 newly characterised HBV-A isolates with 247 reference sequences retrieved from a public database. The phylodynamic reconstruction was performed by a Bayesian framework. The common ancestor of the currently circulating A subgenotypes was placed in west-central Africa a mean 1057 years ago. The genotype diverged into two main clades at the beginning of the 13th century: one including all of the west-central African quasi-subgenotypes and the other corresponding to subgenotype A1, originating in east Africa and further segregating into two main subclades: an "African" and a "cosmopolitan" clade. It is likely that the slave trade was the main source the spread of cosmopolitan HBV-A1, which was exported to Asia in the 17th century as a result of Arab or Portuguese trade, and to Latin America in the 18th centuries through the trans-Atlantic slave trade. The origin of the currently circulating A2 strains dates back to the first decades of the 20th century, and the evolutionary demography analysis suggests an exponential growth of infections, between 1970s and the mid-1990s. In conclusion, the very different epidemiological and evolutionary histories of HBV-A subgenotypes justify the use of different calibration approaches to reconstruct their reciprocal phylodynamics. PMID:25784568

  15. Mutation spectra of the surface-protein-coding region of the HBV genome in HBV-vaccinated and non-vaccinated individuals in Hungary.

    PubMed

    Szomor, Katalin N; Dencs, Agnes; Garai, Eszter; Rusvai, Erzsébet; Berencsi, György; Takács, Mária

    2008-01-01

    Hepatitis B virus (HBV) infection has a major effect on health care systems, with about one-third of the world's population currently infected with the virus. There is an effective vaccine against HBV, which contains a recombinant "surface antigen" produced in an expression vector. Vaccination has proved to be successful in Hungary: the number of acute HBV cases has decreased in the past 10 years. Although an increasing number of publications report on "vaccine-escape" HBV variants which can infect HBV-vaccinated individuals, such mutant HBV strains have not yet been detected in Hungary. We therefore surveyed two risk groups for vaccine-escape or immunoglobulin-escape HBV mutations in Hungary: 28 actively and/or passively HBV-immunized children of HBV carrier mothers who proved to be HBsAg and/or anti-HBc positive and 40 symptomless HBV carrier pregnant women (presumably carrying genotype B or C). We focused on the coding sequences of the "a" immundominant region of the surface protein. We could not detect the G145R amino acid substitution associated with vaccine escape mutant virus. However, we could map other mutations potentially affecting the immunodominant "a" region of the HBV surface protein. PMID:18813870

  16. Towards an HBV cure: state-of-the-art and unresolved questions--report of the ANRS workshop on HBV cure.

    PubMed

    Zeisel, Mirjam B; Lucifora, Julie; Mason, William S; Sureau, Camille; Beck, Jürgen; Levrero, Massimo; Kann, Michael; Knolle, Percy A; Benkirane, Monsef; Durantel, David; Michel, Marie-Louise; Autran, Brigitte; Cosset, François-Loïc; Strick-Marchand, Hélène; Trépo, Christian; Kao, Jia-Horng; Carrat, Fabrice; Lacombe, Karine; Schinazi, Raymond F; Barré-Sinoussi, Françoise; Delfraissy, Jean-François; Zoulim, Fabien

    2015-08-01

    HBV infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Although HBV infection can be efficiently prevented by vaccination, and treatments are available, to date there is no reliable cure for the >240 million individuals that are chronically infected worldwide. Current treatments can only achieve viral suppression, and lifelong therapy is needed in the majority of infected persons. In the framework of the French National Agency for Research on AIDS and Viral Hepatitis 'HBV Cure' programme, a scientific workshop was held in Paris in June 2014 to define the state-of-the-art and unanswered questions regarding HBV pathobiology, and to develop a concerted strategy towards an HBV cure. This review summarises our current understanding of HBV host-interactions leading to viral persistence, as well as the roadblocks to be overcome to ultimately address unmet medical needs in the treatment of chronic HBV infection. PMID:25670809

  17. Prevalence of HBV and HBV vaccination coverage in health care workers of tertiary hospitals of Peshawar, Pakistan

    PubMed Central

    2011-01-01

    Background Hepatitis B Virus (HBV) may progress to serious consequences and increase dramatically beyond endemic dimensions that transmits to or from health care workers (HCWs) during routine investigation in their work places. Basic aim of this study was to canvass the safety of HCWs and determine the prevalence of HBV and its possible association with occupational and non-occupational risk factors. Hepatitis B vaccination coverage level and main barriers to vaccination were also taken in account. Results A total of 824 health care workers were randomly selected from three major hospitals of Peshawar, Khyber Pakhtunkhwa. Blood samples were analyzed in Department of Zoology, Kohat University of Science and Technology Kohat, and relevant information was obtained by means of preset questionnaire. HCWs in the studied hospitals showed 2.18% prevalence of positive HBV. Nurses and technicians were more prone to occupational exposure and to HBV infection. There was significant difference between vaccinated and non-vaccinated HCWs as well as between the doctors and all other categories. Barriers to complete vaccination, in spite of good knowledge of subjects in this regard were work pressure (39.8%), negligence (38.8%) un-affordability (20.9%), and unavailability (0.5%). Conclusions Special preventive measures (universal precaution and vaccination), which are fundamental way to protect HCW against HBV infection should be adopted. PMID:21645287

  18. Low Prevalence of Liver Disease but Regional Differences in HBV Treatment Characteristics Mark HIV/HBV Co-Infection in a South African HIV Clinical Trial

    PubMed Central

    Ive, Prudence; MacLeod, William; Mkumla, Nompumelelo; Orrell, Catherine; Jentsch, Ute; Wallis, Carole L.; Stevens, Wendy; Wood, Robin; Sanne, Ian; Bhattacharya, Debika

    2013-01-01

    Background Hepatitis B virus (HBV) infection is endemic in South Africa however, there is limited data on the degree of liver disease and geographic variation in HIV/HBV coinfected individuals. In this study, we analysed data from the CIPRA-SA ‘Safeguard the household study’ in order to assess baseline HBV characteristics in HIV/HBV co-infection participants prior to antiretroviral therapy (ART) initiation. Methods 812 participants from two South African townships Soweto and Masiphumelele were enrolled in a randomized trial of ART (CIPRA-SA). Participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA. FIB-4 scores were calculated at baseline. Results Forty-eight (5.9%) were HBsAg positive, of whom 28 (58.3%) were HBeAg positive. Of those with HBV, 29.8% had an HBV DNA<2000 IU/ml and ALT<40 IU/ml ; 83.0% had a FIB-4 score <1.45, consistent with absent or minimal liver disease. HBV prevalence was 8.5% in Masiphumelele compared to 3.8% in Soweto (relative risk 2.3; 95% CI: 1.3–4.0). More participants in Masiphumelele had HBeAg-negative disease (58% vs. 12%, p = 0.002) and HBV DNA levels ≤2000 IU/ml, (43% vs. 6% p<0.007). Conclusion One third of HIV/HBV co-infected subjects had low HBV DNA levels and ALT while the majority had indicators of only mild liver disease. There were substantial regional differences in HBsAg and HbeAg prevalence in HIV/HBV co-infection between two regions in South Africa. This study highlights the absence of severe liver disease and the marked regional differences in HIV/HBV co-infection in South Africa and will inform treatment decisions in these populations. PMID:24324573

  19. Occult HBV reactivation induced by ibrutinib treatment: a case report.

    PubMed

    de Jésus Ngoma, Patrick; Kabamba, Benoît; Dahlqvist, Geraldine; Sempoux, Christine; Lanthier, Nicolas; Shindano, Tony; Van Den Neste, Eric; Horsmans, Yves

    2015-12-01

    Ibrutinib is a small molecule that has been recently developped for the treatment of B cell malignancies. Common side effects are diarrhoea, nausea, fatigue, infections, neutropenia and thrombocytopenia. Here we report the first case of Hepatitis B virus reactivation in a 80 years old chronic lymphocytic leukaemia patient receiving ibrutinib, suggesting that such treatment must be associated with HBV screening. PMID:26712054

  20. Association of Periodontal Diseases and Liver Fibrosis in Patients With HCV and/or HBV infection

    PubMed Central

    Nagao, Yumiko; Kawahigashi, Yuji; Sata, Michio

    2014-01-01

    Background: Periodontal disease and systemic health are closely associated. However, there is no data supporting the association between periodontal disease and patients with liver diseases associated with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) infection. Objectives: The aim of this study was to evaluate the association between periodontitis and progression of liver diseases in patients with HCV and/or HBV infection. Patients and Methods: In this retrospective study, 351 patients with HCV- and/or HBV-related liver diseases underwent screening for periodontal disease using the Salivaster® salivary occult blood test from February 2010 to June 2014. Furthermore, we examined the prevalence of fimbrillin (fimA) genotype of Porphyromonas gingivalis (P. gingivalis) in 28 HCV-infected patients visited at our hospital between January 2013 and June 2014. P. gingivalis with fimA genotype with types I to V was further detected using a PCR method. Results: Of 351 patients, 76 patients (group 1) had a strong positive result for salivary occult blood test and 275 patients (group 2) had weak positive or negative test results. Significant factors between the groups were obesity, level of AST, ALT, LDH, ALP, Alb, D.Bil, T.cho, AFP, platelets (Plt), IRI, HOMA-IR, current interferon (IFN) treatment and the daily frequency of tooth brushing. Between-groups analysis indicated that total protein (T.pro) level and liver fibrosis were significant factors. According to multivariate analysis, five factors were associated with periodontal disease as Plt count below 80000, brushing teeth only once a day, current IFN treatment, aged 65 years or older and obesity. The adjusted odds ratios for these five factors were 5.80, 3.46, 2.87, 2.50 and 2.33, respectively, and each was statistically significant. Twenty-eight saliva specimens had positive results for P. gingivalis with fimA genotype types I to V. The prevalence of fimA genotype II was higher in 14 patients with liver

  1. Construction and Immunological Evaluation of Multivalent Hepatitis B Virus (HBV) Core Virus-Like Particles Carrying HBV and HCV Epitopes▿

    PubMed Central

    Sominskaya, Irina; Skrastina, Dace; Dislers, Andris; Vasiljev, Denis; Mihailova, Marija; Ose, Velta; Dreilina, Dzidra; Pumpens, Paul

    2010-01-01

    A multivalent vaccine candidate against hepatitis B virus (HBV) and hepatitis C virus (HCV) infections was constructed on the basis of HBV core (HBc) virus-like particles (VLPs) as carriers. Chimeric VLPs that carried a virus-neutralizing HBV pre-S1 epitope corresponding to amino acids (aa) 20 to 47 in the major immunodominant region (MIR) and a highly conserved N-terminal HCV core epitope corresponding to aa 1 to 60 at the C terminus of the truncated HBcΔ protein (N-terminal aa 1 to 144 of full-length HBc) were produced in Escherichia coli cells and examined for their antigenicity and immunogenicity. The presence of two different foreign epitopes within the HBc molecule did not interfere with its VLP-forming ability, with the HBV pre-S1 epitope exposed on the surface and the HCV core epitope buried within the VLPs. After immunization of BALB/c mice, specific T-cell activation by both foreign epitopes and a high-titer antibody response against the pre-S1 epitope were found, whereas an antibody response against the HBc carrier was notably suppressed. Both inserted epitopes also induced a specific cytotoxic-T-lymphocyte (CTL) response, as shown by the gamma interferon (IFN-γ) production profile. PMID:20410327

  2. 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

  3. HBV Outreach Programs Significantly Increase Knowledge and Vaccination Rates Among Asian Pacific Islanders.

    PubMed

    Zacharias, Tresa; Wang, Winnie; Dao, Doan; Wojciechowski, Helena; Lee, William M; Do, Son; Singal, Amit G

    2015-08-01

    Hepatitis B virus (HBV) testing and vaccination rates remain low among Asian-American/Pacific Islanders (APIs) despite high rates of HBV infection. The aim of our study was to assess the effectiveness of an outreach campaign to increase HBV knowledge, testing, and vaccination among a cohort of APIs. Vietnamese Americans were invited to participate in a free HBV screening and vaccination outreach program though pubic service announcements. Attendees completed a survey to assess barriers to vaccination and HBV-related knowledge before and after a 30-min education session by a bilingual board-certified gastroenterologist. Among 98 participants, 100% (22/22) of HBV naïve patients were provided a HBV vaccination series at no cost and over 75% (14/18) of HBV-infected patients were connected to further medical care. Notable reported barriers to prior testing and/or vaccination were cost of the vaccine, concern about missing work for evaluation, and lack of provider recommendation. Knowledge levels about HBV risk factors, potential consequences, and treatment options were poor at baseline but significantly increased after the education session (49 vs. 64%, p < 0.001). Outreach campaigns linked with education can successfully address several barriers to HBV testing and offer an approach to improve HBV awareness and prevention among difficult-to-reach populations. PMID:25476035

  4. Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon

    PubMed Central

    Bivigou-Mboumba, Berthold; François-Souquière, Sandrine; Deleplancque, Luc; Sica, Jeanne; Mouinga-Ondémé, Augustin; Amougou-Atsama, Marie; Chaix, Marie-Laure; Njouom, Richard; Rouet, François

    2016-01-01

    Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010–2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%–2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%–3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%–7.8%). Sixty-one (8.0%; 95% CI, 6.2%–10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB. PMID:26764909

  5. Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon.

    PubMed

    Bivigou-Mboumba, Berthold; François-Souquière, Sandrine; Deleplancque, Luc; Sica, Jeanne; Mouinga-Ondémé, Augustin; Amougou-Atsama, Marie; Chaix, Marie-Laure; Njouom, Richard; Rouet, François

    2016-01-01

    Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%-2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%-3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%-7.8%). Sixty-one (8.0%; 95% CI, 6.2%-10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB. PMID:26764909

  6. Comparison of the effects of formaldehyde and gaseous ozone on HBV-contaminated hospital quilts

    PubMed Central

    Guo, Dan; Li, Ziqiong; Jia, Bei; Che, Xiaoqiong; Song, Tianshuang; Huang, Wenxiang

    2015-01-01

    Background: Besides being highly infectious, Hepatitis B virus (HBV) is a major cause of liver disease worldwide. In hospital settings, it is easy for the environment and quilts to be contaminated by HBV patient blood and body fluids. Therefore, HBV can be transmitted to other patients via contaminated environmental surfaces or quilts, resulting in an HBV nosocomial infection. Formaldehyde and ozone are commonly used disinfectants that may influence this infectious situation. Objective: To investigate the clinical effectiveness of formaldehyde and gaseous ozone for the terminal cleaning of hospital quilts contaminated by HBV. Methods: Thin cloth and thick cotton soaked with the serum from high HBV copy number patients were prepared and disinfected using formaldehyde fumigation and gaseous ozone at different times. The copy numbers of HBV DNA in the HBV-contaminated cloth and cotton samples were measured quantitatively with fluorescent quantitative polymerase chain reaction (PCR). Results: When gaseous ozone was used to disinfect HBV-contaminated quilts for 23 minutes (min), 36 min, 49 min, and 90 min, the HBV DNA copy number displayed no significant decrease compared with the copy number before disinfection (P > 0.05). In comparison, the copy number of the HBV DNA in the cloth group decreased significantly (P < 0.05) after formaldehyde fumigation disinfection for 1 hour (h), and there was no difference when longer times and increased concentrations were used. In the thick cotton group, there was also a significant decrease (P < 0.05) of the HBV DNA copy numbers, but the decrease was not as dramatic. In addition, in this group, the disinfection effect observed at 4 h was the strongest. Conclusions: The application of ozone to disinfect HBV-contaminated hospital quilts possibly has no effect, whereas, formaldehyde oxide fumigation effectively reduced HBV copy numbers. PMID:26770591

  7. Molecular Characterization of HBV Strains Circulating among the Treatment-Naive HIV/HBV Co-Infected Patients of Eastern India

    PubMed Central

    Saha, Debraj; Pal, Ananya; Biswas, Avik; Panigrahi, Rajesh; Sarkar, Neelakshi; Das, Dipanwita; Sarkar, Jayeeta; Guha, Subhasish Kamal; Saha, Bibhuti; Chakrabarti, Sekhar; Chakravarty, Runu

    2014-01-01

    Previously we reported that the exposure to hepatitis B virus (HBV) infection serves as a major threat among the treatment naive HIV infected population of eastern India. Hence, molecular characterization of these strains is of utmost importance in order to identify clinically significant HBV mutations. A total of 85 treatment naive HIV/HBV co-infected participants were included of whom the complete basal core promoter/precore region, the core and the whole envelope gene could be successfully sequenced for 59, 57 and 39 isolates respectively. Following phylogenetic analysis, it was found that HBV/D was the predominant genotype with HBV/D2 (38.5%) being the most prevalent subgenotype followed by HBV/A1. The major mutations affecting HBeAg expression includes the A1762T/G1764A (13.6%), G1896A (22%) and G1862T mutation (33.9%) which was predominantly associated with HBV/A1. Moreover, the prevalence of G1896A was considerably high among the HBeAg negative HIV/HBV co-infected subjects compared to HBV mono-infection. The main amino acid substitutions within the MHC class II restricted T-cell epitope of HBcAg includes the T12S (15.8%) and T67N (12.3%) mutation and the V27I (10.5%) mutation in the MHC class I restricted T-cell epitope. PreS1/S2 deletion was detected in 3 isolates with all harboring the BCP double mutation. Furthermore, the frequently occurring mutations in the major hydrophilic loop of the S gene include the T125M, A128V and M133I/L. Therefore, this study is the first from India to report useful information on the molecular heterogeneity of the HBV strains circulating among the treatment naive HIV/HBV co-infected population and is thus clinically relevant. PMID:24587360

  8. HBV influence on Response to Antiretroviral Therapy in Horizontally HIV-HBV Coinfected Patient during Early Childhood

    PubMed Central

    Niculescu, Irina; Cupşa, A.M.; Stoian, Andreea Cristina; Dumitrescu, FLorentina; Giubelan, L.I.; Alexandru, D.O.

    2013-01-01

    Background: There are few studies on pediatric HIV-HBV coinfection, so evidences about relationships between the two viruses are scarce. Objectives: influence of HBV infection on virological and immunological response to antiretroviral therapy (ART) in antiretroviral-naïve horizontally HIV-HBV coinfected subjects during early childhood. Material and methods: observational study on 826 HIV+ subjects in evidence of Craiova Regional Centre (CRC); we analyzed the immunological and virological response at 6-12 months after starting first antiretroviral regimens compared in 2 groups: horizontally HIV-HBV coinfected subjects during early childhood (CoS) versus horizontally HIV infected subjects during early childhood without HBV infection (non-CoS). Results: Number of subjects: CoS-66 subjects, non-CoS-132 subjects. Demographic data: CoS-gender ratio F:M=0.886, the majority lived in rural area (57.58%), mean age on diagnosis-9.288±4.607 years, non-CoS-gender ratio F:M=0.859, the majority lived in urban area (53.79%), mean age on diagnosis-10.742±5.107 years. At baseline, HIV category was: CoS-A-1.52%, B-80.30%, C-18.18%, non-CoS-A-2.27%, B-70.45%, C-27.27% (p Chi2=0.332), the mean CD4+ cell count was: CoS-148.33±148.10 cells/ml, non-CoS-163.17±155.39 cells/ml (p Student=0.521) and the mean HIV viral load (HIV VL) was: CoS-5.06±0.80 lgcopies/ml (for 29 subjects), non-CoS-5.04±0.84 lgcopies/ml (for 61 subjects) (p Student=0.978). At the end of the studied period, the mean increase in CD4+ cell count was: CoS-177.068±141.676 cells/ml, non-CoS-176.015±191.751 cells/ml (p Student=0.969) and the mean decrease in HIV VL was: CoS-5.04±0.79 lgcopies/ml, non-COS-4.69±2.04 lgcopies/ml (p Student=0.911). Conclusions: The presence of HBV coinfection does not influence immunological or virological response to ART. PMID:24778861

  9. Core protein: a pleiotropic keystone in the HBV lifecycle

    PubMed Central

    Zlotnick, Adam; Venkatakrishnan, Balasubramanian; Tan, Zhenning; Lewellyn, Eric; Turner, William; Francis, Samson

    2015-01-01

    Hepatitis B Virus (HBV) is a small virus whose genome has only four open reading frames. We argue that the simplicity of the virion correlates with a complexity of functions for viral proteins. We focus on the HBV core protein (Cp), a small (183 residue) protein that self-assembles to form the viral capsid. However, its functions are a little more complicated than that. In an infected cell Cp modulates every step of the viral lifecycle. Cp is bound to nuclear viral DNA and affects its epigenetics. Cp correlates with RNA specificity. Cp assembles specifically on a reverse transcriptase-viral RNA complex or, apparently, nothing at all. Indeed Cp has been one of the model systems for investigation of virus self-assembly. Cp participates in regulation of reverse transcription. Cp signals completion of reverse transcription to support virus secretion. Cp carries both nuclear localization signals and HBV surface antigen (HBsAg) binding sites; both of these functions appear to be regulated by contents of the capsid. Cp can be targeted by antivirals -- while self-assembly is the most accessible of Cp activities, we argue that it makes sense to engage the broader spectrum of Cp function. This article forms part of a symposium in Antiviral Research on “From the discovery of the Australia antigen to the development of new curative therapies for hepatitis B: an unfinished story.” PMID:26129969

  10. Occult HBV Infection: A Faceless Enemy in Liver Cancer Development

    PubMed Central

    Morales-Romero, Jaime; Vargas, Gustavo; García-Román, Rebeca

    2014-01-01

    The hepatitis B virus (HBV) represents a worldwide public health problem; the virus is present in one third of the global population. However, this rate may in fact be higher due to occult hepatitis B virus infection (OBI). This condition is characterized by the presence of the viral genome in the liver of individuals sero-negative for the virus surface antigen (HBsAg). The causes of the absence of HBsAg in serum are unknown, however, mutations have been identified that produce variants not recognized by current immunoassays. Epigenetic and immunological host mechanisms also appear to be involved in HBsAg suppression. Current evidence suggests that OBI maintains its carcinogenic potential, favoring the progression of fibrosis and cirrhosis of the liver. In common with open HBV infection, OBI can contribute to the establishment of hepatocellular carcinoma. Epidemiological data regarding the global prevalence of OBI vary due to the use of detection methods of different sensitivity and specificity. In Latin America, which is considered an area of low prevalence for HBV, diagnostic screening methods using gene amplification tests for confirmation of OBI are not conducted. This prevents determination of the actual prevalence of OBI, highlighting the need for the implementation of cutting edge technology in epidemiological surveillance systems. PMID:24717680

  11. The intracellular dynamics of hepatitis B virus (HBV) replication with reproduced virion "re-cycling".

    PubMed

    Nakabayashi, Jun

    2016-05-01

    Hepatitis B virus (HBV) is a causative agent of hepatitis. Clinical outcome of hepatitis type B depends on the viral titer observed in the peripheral blood of the patient. In the chronic hepatitis patient, production of HBV virion remains low level. On the other hand, the viral load prominently increases in fulminant hepatitis patient as compared with that in the chronic hepatitis patient. We previously proposed a mathematical model describing the intracellular dynamics of HBV replication. Our model clarified that there are two distinguishable replication patterns of HBV named "arrested" and "explosive" replication. In the arrested replication, the amount of virion newly reproduced from an infected cell remains low level, while the amount of virion extremely increases in the explosive replication. Viral load is drastically changed by slight alteration of expression ratio of 3.5kb RNA to 2.4kb mRNA of HBV. Though our model provided the switching mechanism determining the replication pattern of HBV, HBV dynamics is determined by not only the expression pattern of viral genes. In this study, "recycling" of HBV virion in the replication cycle is investigated as a new factor affecting the intracellular dynamics of HBV replication. A part of newly produced virion of HBV is reused as a core particle that is a resource of HBV replication. This recycling of HBV virion lowers the threshold for the explosive replication when waiting time for the next cycle of the replication is large. It is seemingly contradicting that prominent production of HBV is caused by large recycling rate and small release rate of HBV virion from infected cell to extracellular space. But the recycling of HBV virion can contribute to the positive feedback cycle of HBV replication for the explosive replication to accumulate the core particle as a resource of HBV replication in an infected cell. Accumulation of core particle in the infected cell can be risk factor for the exacerbation of hepatitis rather

  12. Levamisole is a potential facilitator for the activation of Th1 responses of the subunit HBV vaccination.

    PubMed

    Zhang, Wenjuan; Du, Xiaogang; Zhao, Gang; Jin, Huali; Kang, Youmin; Xiao, Chong; Liu, Mingyu; Wang, Bin

    2009-08-01

    Chemical compounds activating innate responses may present potential adjuvants for the vaccine development. Levamisole (LMS), demonstrated as a potent adjuvant for DNA and viral killed vaccines in our previous studies, may activate such responses. To confirm this notion, LMS combined with the recombinant HBsAg (rHBsAg) was investigated. Compared to the vaccination with rHBsAg alone, LMS could up-regulate the expressions of TLR7&8, MyD88, IRF7 and their downstream pro-inflammatory cytokines including IFN-alpha and TNF-alpha, which promote DCs activation. Strikingly, we find that the combination of LMS and alum adjuvant synergistically enhances immunogenicity of rHBsAg and leads to a robust cell-mediated response demonstrated by the higher level of IgG2a/IgG1, T cell proliferation, and importantly, a high level of antigen-specific CTL and IFN-gamma production within these activated CD8(+) T cells. The achieved robust responses are at a comparative level with CpG+alum used as a positive control adjuvant in mice. The combination of LMS+alum with rHBsAg may provide a cost-effective, safe, and effective therapy to treat those individuals chronically infected by HBV, since antigen-specific cellular immunity is implicated for the clearance of HBV chronic infection. PMID:19549606

  13. Recognition and management of HBV infection in a social context.

    PubMed

    Lee, Haeok; Hann, Hie-Won; Yang, Jin Hyang; Fawcett, Jacqueline

    2011-09-01

    Chronic viral hepatitis B and C infection is three to five times more frequent than HIV in the USA, and chronically infected people are at risk for long-term sequelae including cirrhosis, liver decomposition, and hepatocellular carcinoma (Institute of Medicine, 2010). Socio-cultural factors are central to the way an individual constructs hepatitis B virus (HBV) infection, perceives it as serious health problem, and moves on to appropriate health behavior (Lee et al., J Canc Educ 25:337-342, 2010; Kim, J Health Care Poor Underserved 5:170-182, 2004; Lee et al., Asian Nurs Res 1:1-11, 2007; Wu et al, Asian Pac J Cancer Prev 8(1):127-234, 2007; Yang et al., J Korean Academy Nurs 40:662-675, 2010). The purpose of this study was to seek "real world" data about factors that influence the recognition and management of HBV infection in Korean Americans' socio-cultural contexts. The descriptive qualitative study used an interview informed by ethnography to collect data and was guided by the Network-Episode Model. (Pescosolido, Adv Med Sociol 2:161-184, 1991; Pescosolido, AJS 97:1096-1138, 1992; Pescosolido, Res Sociol Health Care 13A:171-197, 1996). The sample comprised 12 HBV patients and nine key informants. Six factors that influenced the management of HBV infection emerged from the interviews: recognition of disease within a social context, unrecognized disease in a hidden health system, the socio-cultural meaning of disease, lay construction of the cause of disease, misunderstandings and cultural learning styles, and personal and environmental barriers to health care. Each theme was associated with Korean American (KA) social contexts, participants' experiences, and the beliefs they held about the disease. The findings explored that the family network is "genetic code" for social networking among KAs and the network of patients was not geographically bound. Health management behaviors are mediated by an array of types and levels of social and personal networks, and

  14. Clonorchis sinensis Co-infection Could Affect the Disease State and Treatment Response of HBV Patients

    PubMed Central

    Huang, Yan; Chen, Tingjin; Kong, Xiangzhan; Sun, Hengchang; Yu, Xinbing; Xu, Jin

    2016-01-01

    Background Clonorchis sinensis (C. sinensis) is considered to be an important parasitic zoonosis because it infects approximately 35 million people, while approximately 15 million were distributed in China. Hepatitis B virus (HBV) infection is a major public health issue. Two types of pathogens have the potential to cause human liver disease and eventually hepatocellular carcinoma. Concurrent infection with HBV and C. sinensis is often observed in some areas where C. sinensis is endemic. However, whether C. sinensis could impact HBV infection or vice versa remains unknown. Principal Findings Co-infection with C. sinensis and HBV develops predominantly in males. Co-infected C. sinensis and HBV patients presented weaker liver function and higher HBV DNA titers. Combination treatment with antiviral and anti-C. sinensis drugs in co-infected patients could contribute to a reduction in viral load and help with liver function recovery. Excretory-secretory products (ESPs) may, in some ways, increase HBV viral replication in vitro. A mixture of ESP and HBV positive sera could induce peripheral blood mononuclear cells (PBMCs) to produce higher level of Th2 cytokines including IL-4, IL-6 and IL-10 compared to HBV alone, it seems that due to presence of ESP, the cytokine production shift towards Th2. C. sinensis/HBV co-infected patients showed higher serum IL-6 and IL-10 levels and lower serum IFN-γ levels. Conclusions/Significance Patients with concomitant C. sinensis and HBV infection presented weaker liver function and higher HBV DNA copies. In co-infected patients, the efficacy of anti-viral treatment was better in patients who were prescribed with entecavir and praziquantel than entecavir alone. One possible reason for the weaker response to antiviral therapies in co-infected patients was the shift in cytokine production from Th1 to Th2 that may inhibit viral clearance. C. sinensis/HBV co-infection could exacerbate the imbalance of Th1/Th2 cytokine. PMID:27348302

  15. HBV is a risk factor for poor patient prognosis after curative resection of hepatocellular carcinoma

    PubMed Central

    Li, Zhonghu; Zhao, Xin; Jiang, Peng; Xiao, Senlin; Wu, Guo; Chen, Kai; Zhang, Xi; Liu, Hui; Han, Xiuguo; Wang, Shuguang; Li, Xiaowu

    2016-01-01

    Abstract Controversy exists regarding pathological factors affecting the prognosis of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV-HCC). Their postoperative clinical behaviors and the exact HBV Deoxyribonucleic Acid (DNA) thresholds that distinguish good and poor prognoses are unknown. This study aimed to compare clinicopathological, pre- and postoperative clinical factors and overall and recurrence-free survival (RFS) between HBV-HCC patients and nonhepatitis B and nonhepatitis C HCC (NBC-HCC) patients to determine the optimal prognostic HBV DNA threshold. Data from 1440 patients with HBV-HCC and NBC-HCC who underwent curative hepatectomy were retrospectively analyzed. Liver function in the HBV-HCC group was significantly worse than in the NBC-HCC group. Compared with NBC-HCC patients, HBV-HCC patients had significantly more vascular invasion and advanced HCC. The HBV-HCC patients also had significantly worse liver function and more complications. Further survival analysis showed significantly lower overall and RFS rates and a higher early recurrence rate in the HBV-HCC group. Univariate analysis indicated that HBV was a risk factor for overall and RFS. Finally, X-tile analysis revealed that the optimal HBV DNA cutoff points for predicting RFS and overall survival in HCC patients were 10,100 and 12,800 IU/mL, respectively. After hepatectomy for HCC, HBV-HCC patients had more complications and a worse prognosis than NBC-HCC patients. Antiviral therapy should be considered before hepatectomy in patients with high (more than approximately 104 IU/mL) HBV DNA levels. PMID:27495026

  16. Chimeric hepatitis B virus (HBV)/hepatitis C virus (HCV) subviral envelope particles induce efficient anti-HCV antibody production in animals pre-immunized with HBV vaccine.

    PubMed

    Beaumont, Elodie; Roingeard, Philippe

    2015-02-18

    The development of an effective, affordable prophylactic vaccine against hepatitis C virus (HCV) remains a medical priority. The recently described chimeric HBV-HCV subviral envelope particles could potentially be used for this purpose, as they could be produced by industrial procedures adapted from those established for the hepatitis B virus (HBV) vaccine. We show here, in an animal model, that pre-existing immunity acquired through HBV vaccination does not influence the immunogenicity of the HCV E2 protein presented by these chimeric particles. Thus, these chimeric HBV-HCV subviral envelope particles could potentially be used as a booster in individuals previously vaccinated against HBV, to induce protective immunity to HCV. PMID:25596457

  17. Current Concepts of HBV/HCV Coinfection: Coexistence, but Not Necessarily in Harmony

    PubMed Central

    Jamma, Shailaja; Hussain, Ghazi; Lau, Daryl T.-Y.

    2011-01-01

    Hepatitis B and hepatitis C are important causes of chronic liver disease globally. Although HBV/HCV coinfection is not uncommon, its epidemiology is poorly defined. Numerous studies provided evidence that coinfection accelerates liver disease progression and increases the risk of hepatocellular carcinoma. By applying new cell culture models to examine the interaction of both viruses, investigators concluded that HBV and HCV replicate in the same hepatocyte without interference. The roles of innate and adaptive immunity in determining the viral replication and disease outcomes still need rigorous investigation. To date, no standard-of-care recommendation exists for HBV/HCV coinfection. Pegylated interferon and ribavirin combination therapy demonstrated similar efficacy in suppressing HCV RNA in coinfection and HCV monoinfection. However, HBV reactivation during therapy can be a challenge. Future clinical trials evaluating the addition of a nucleoside/nucleotide analog for selective patients with HBV/HCV coinfection are essential for successful management of HBV/HCV coinfection. PMID:21258658

  18. Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α

    PubMed Central

    Dai, Xiaopeng; Zhang, Wei; Zhang, Hongfei; Sun, Shihui; Yu, Hong; Guo, Yan; Kou, Zhihua; Zhao, Guangyu; Du, Lanying; Jiang, Shibo; Zhang, Jianying; Li, Junfeng; Zhou, Yusen

    2014-01-01

    Hepatitis B virus (HBV) infection remains a major health problem worldwide. The role played by microRNAs (miRNAs) in HBV replication and pathogenesis is being increasingly recognized. In this study, we found that miR-15b, an important miRNA during HBV infection and hepatocellular carcinoma development, directly binds hepatocyte nuclear factor 1α (HNF1α) mRNA, a negative regulator of HBV Enhancer I, to attenuate HNF1α expression, resulting in transactivation of HBV Enhancer I, in turn causing the enhancement of HBV replication and expression of HBV antigens, including HBx protein, finally leading to the down-regulated expression of miR-15b in both cell lines and mice in a long cascade of events. Our research showed that miR-15b promotes HBV replication by augmenting HBV Enhancer I activity via direct targeting HNF1α, while HBV replication and antigens expression, particularly the HBx protein, then repress the expression of miR-15b. The reciprocal regulation between miR-15b and HBV controls the level of HBV replication and might play a role in persistent HBV infection. This work adds to the body of knowledge concerning the complex interactions between HBV and host miRNAs. PMID:24705650

  19. Gluconeogenesis, lipogenesis, and HBV replication are commonly regulated by PGC-1α-dependent pathway

    PubMed Central

    Lin, Kuan-Ting; Hsu, Shih-Lan; Wang, Feng-Sheng; Chou, Chen-Kung; Lee, Kuen-Haur; Tsou, Ann-Ping; Lai, Jin-Mei; Yeh, Sheau-Farn; Huang, Chi-Ying F.

    2015-01-01

    PGC-1α, a major metabolic regulator of gluconeogenesis and lipogenesis, is strongly induced to coactivate Hepatitis B virus (HBV) gene expression in the liver of fasting mice. We found that 8-Br-cAMP and glucocorticoids synergistically induce PGC-1α and its downstream targets, including PEPCK and G6Pase. Also, HBV core promoter activity was synergistically enhanced by 8-Br-cAMP and glucocorticoids. Graptopetalum paraguayense (GP), a herbal medicine, is commonly used in Taiwan to treat liver disorders. Partially purified fraction of GP (named HH-F3) suppressed 8-Br-cAMP/glucocorticoid-induced G6Pase, PEPCK and PGC-1α expression and suppressed HBV core promoter activity. HH-F3 blocked HBV core promoter activity via inhibition of PGC-1α expression. Ectopically expressed PGC-1α rescued HH-F3-inhibited HBV surface antigen expression, HBV mRNA production, core protein levels, and HBV replication. HH-F3 also inhibited fatty acid synthase (FASN) expression and decreased lipid accumulation by down-regulating PGC-1α. Thus, HH-F3 can inhibit HBV replication, gluconeogenesis and lipogenesis by down-regulating PGC-1α. Our study indicates that targeting PGC-1α may be a therapeutic strategy for treatment of HBV infections. HH-F3 may have potential use for the treatment of chronic hepatitis B patients with associated metabolic syndrome. PMID:25762623

  20. ZEB2 inhibits HBV transcription and replication by targeting its core promoter

    PubMed Central

    Ren, Jihua; Huang, Yecai; Huang, Ying; Hu, Qin; Chen, Juan; Chen, Weixian

    2016-01-01

    Hepatitis B virus (HBV) infection is a major cause of liver diseases, especially liver cirrhosis and hepatocellular carcinoma. However, the interaction between host and HBV has not been fully elucidated. ZEB2 is a Smad-interacting, multi-zinc finger protein that acts as a transcription factor or repressor for several signaling pathways. This study found that the expression of ZEB2 was decreased in HBV-expressing cells. Overexpression of ZEB2 inhibited HBV DNA replicative intermediates, 3.5kb mRNA, core protein level, and the secretion of HBsAg and HBeAg. In contrast, ZEB2 knockdown promoted HBV replication. Furthermore, ZEB2 could bind to HBV core promoter and inhibit its promoter activity. Mutation at the ZEB2 binding site in HBV core promoter eradicated ZEB2-mediated inhibition of HBV replication. This study identifies ZEB2 as a novel host restriction factor that inhibits HBV replication in hepatocytes. These data may shed light on development of new antiviral strategies. PMID:26895378

  1. High prevalence of human parvovirus 4 infection in HBV and HCV infected individuals in shanghai.

    PubMed

    Yu, Xuelian; Zhang, Jing; Hong, Liang; Wang, Jiayu; Yuan, Zhengan; Zhang, Xi; Ghildyal, Reena

    2012-01-01

    Human parvovirus 4 (PARV4) has been detected in blood and diverse tissues samples from HIV/AIDS patients who are injecting drug users. Although B19 virus, the best characterized human parvovirus, has been shown to co-infect patients with hepatitis B or hepatitis C virus (HBV, HCV) infection, the association of PARV4 with HBV or HCV infections is still unknown.The aim of this study was to characterise the association of viruses belonging to PARV4 genotype 1 and 2 with chronic HBV and HCV infection in Shanghai.Serum samples of healthy controls, HCV infected subjects and HBV infected subjects were retrieved from Shanghai Center for Disease Control and Prevention (SCDC) Sample Bank. Parvovirus-specific nested-PCR was performed and results confirmed by sequencing. Sequences were compared with reference sequences obtained from Genbank to derive phylogeny trees.The frequency of parvovirus molecular detection was 16-22%, 33% and 41% in healthy controls, HCV infected and HBV infected subjects respectively, with PARV4 being the only parvovirus detected. HCV infected and HBV infected subjects had a significantly higher PARV4 prevalence than the healthy population. No statistical difference was found in PARV4 prevalence between HBV or HCV infected subjects. PARV4 sequence divergence within study groups was similar in healthy subjects, HBV or HCV infected subjects.Our data clearly demonstrate that PARV4 infection is strongly associated with HCV and HBV infection in Shanghai but may not cause increased disease severity. PMID:22235298

  2. Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 to Enhance HBV Replication.

    PubMed

    Murphy, Christopher M; Xu, Yanping; Li, Feng; Nio, Kouki; Reszka-Blanco, Natalia; Li, Xiaodong; Wu, Yaxu; Yu, Yanbao; Xiong, Yue; Su, Lishan

    2016-09-13

    The hepatitis B virus (HBV) regulatory protein X (HBx) activates gene expression from the HBV covalently closed circular DNA (cccDNA) genome. Interaction of HBx with the DDB1-CUL4-ROC1 (CRL4) E3 ligase is critical for this function. Using substrate-trapping proteomics, we identified the structural maintenance of chromosomes (SMC) complex proteins SMC5 and SMC6 as CRL4(HBx) substrates. HBx expression and HBV infection degraded the SMC5/6 complex in human hepatocytes in vitro and in humanized mice in vivo. HBx targets SMC5/6 for ubiquitylation by the CRL4(HBx) E3 ligase and subsequent degradation by the proteasome. Using a minicircle HBV (mcHBV) reporter system with HBx-dependent activity, we demonstrate that SMC5/6 knockdown, or inhibition with a dominant-negative SMC6, enhance HBx null mcHBV-Gluc gene expression. Furthermore, SMC5/6 knockdown rescued HBx-deficient HBV replication in human hepatocytes. These results indicate that a primary function of HBx is to degrade SMC5/6, which restricts HBV replication by inhibiting HBV gene expression. PMID:27626656

  3. A fusion DNA vaccine encoding middle version of HBV envelope protein fused to interleukin-21 did not enhance HBV-specific immune response in mice.

    PubMed

    Zhang, Ye; Su, Wen-Jing; Wang, Jue; Bai, Xue-Fan; Huang, Chang-Xing; Lian, Jian-Qi

    2014-11-01

    DNA vaccination can generate both humoral and cellular immunity, resulting in potential prophylactic and therapeutic vaccines in variety of conditions, including hepatitis B virus (HBV) infection. Fusion of cytokine gene is one of the ways to increase the immunogenicity of DNA vaccine. Interleukin (IL)-21 has been demonstrated to play an immunomodulatory role in HBV infection. Thus, we aimed to investigate the ability of IL-21 in the regulation of middle version of HBV envelop protein (MS) DNA vaccine. Fusion plasmid encoding IL-21 linked with MS was constructed. Normal and HBV transgenic mice were immunized by plasmid. pcDNA-IL-21/S2S induced a comparable level of anti-HBs antibody and HBsAg-specific CD8+ T-cell response with pcDNA-S2S. Furthermore, the level of circulating HBsAg was decreased by induction of anti-HBs antibody and HBsAg-specific CD8+ T-cell response to both pcDNA-IL-21/S2S and pcDNA-S2S vaccination in HBV transgenic mice. Thus, immunization with DNA vaccine encoding HBV MS protein induced both T- and B-cell response by targeting the specific antigen. Furthermore, it was also revealed that MS DNA vaccination could break immune tolerance in HBV transgenic mice. But IL-21 did not strengthen immune response induced by HBV DNA immunization. Our study suggested that MS-expressing plasmid may be useful for both preventive and therapeutic methods in HBV infection. However, IL-21 does not improve the immunogenicity and efficacy of MS DNA vaccination, and thus may not be used as a therapeutic marker for chronic hepatitis B. PMID:25211639

  4. Spectroscopic investigations of HBV 475 in optical regions

    SciTech Connect

    Tamura, Shinichi )

    1989-03-01

    High-resolution spectroscopic analyses of HBV 475 are presented based on emission-line profiles of H-alpha, H-gamma, He I 4921-A, He I 5016-A, forbidden O III 4959-A, 5007-A, Fe II 5018-A, and Fe II 4924-A. Radial-velocity analyses show that only a part of the line components coincides well with previous measurements. Other remarkable components are found which are shifted to either the violet or red sides, depending on the indicated phase. Highly resolved emission-line profiles reveal that they are not compatible with the calculated profiles of proposed theoretical models. 21 refs.

  5. HBV carriage in children born from HIV-seropositive mothers in Senegal: The need of birth-dose HBV vaccination.

    PubMed

    Gueye, Sokhna Bousso; Diop-Ndiaye, Halimatou; Lo, Gora; Mintsa, Sandrine; Guindo, Ibrahima; Dia, Aminata; Sow-Sall, Amina; Gaye-Diallo, Aissatou; Mboup, Souleymane; Touré-Kane, Coumba

    2016-05-01

    Hepatitis B is a major public health problem in Senegal, a country with high prevalence and a transmission occurring mainly during infancy. Only, one 6-8 weeks vaccination campaign was initiated in 2005 and it was part of the expanded program of immunization. The aim of this study was to determine the prevalence of HBsAg in children born from HIV-seropositive mothers by using dried blood specimens. Specimens were collected between July 2007 and November 2012 from children aged 2-48 weeks in Dakar and decentralized sites working on HIV mother-to-child transmission prevention. HBsAg detection was performed using Architect HBsAg Qualitative II kit (Abbott Diagnostics, Ireland) and for all reactive samples confirmation was done using Architect HBsAg Qualitative II Confirmatory kit (Abbott Diagnostics, Ireland). Nine hundred thirty samples were collected throughout the country with 66% out of Dakar, the capital city. The median age was 20 weeks and 88% of children were less than 1 year of age with a sex ratio of 1.27 in favor of boys. HBsAg was detected in 28 cases giving a global prevalence of 3%. According to age, HBsAg prevalences were 5.1% for children less than 6 weeks, 4.1% and 4.6%, respectively, for those aged 12-18 weeks and 18-24 weeks of age. The HIV prevalence was 2.6% with no HIV/HBV co-infection. This study showed a high rate of HBV infection in children under 24 months, highlighting the need to promote birth-dose HBV vaccination as recommended by WHO. PMID:26488892

  6. Integration of tumour and viral genomic characterisations in HBV-related hepatocellular carcinomas

    PubMed Central

    Amaddeo, Giuliana; Cao, Qian; Ladeiro, Yannick; Imbeaud, Sandrine; Nault, Jean-Charles; Jaoui, Daphne; Gaston Mathe, Yann; Laurent, Christophe; Laurent, Alexis; Bioulac-Sage, Paulette; Calderaro, Julien; Zucman-Rossi, Jessica

    2015-01-01

    Background and aim Hepatocellular carcinoma (HCC) is the most common liver cancer. We characterised HCC associated with infection compared with non-HBV-related HCC to understand interactions between viral and hepatocyte genomic alterations and their relationships with clinical features. Methods Frozen HBV (n=86) or non-HBV-related (n=90) HCC were collected in two French surgical departments. Viral characterisation was performed by sequencing HBS and HBX genes and quantifying HBV DNA and cccDNA. Nine genes were screened for somatic mutations and expression profiling of 37 genes involved in hepatocarcinogenesis was studied. Results HBX revealed frequent non-sense, frameshift and deletions in tumours, suggesting an HBX inactivation selected in HCC. The number of viral copies was frequently lower in tumour than in non-tumour tissues (p=0.0005) and patients with low HBV copies in the non-tumour liver tissues presented additional risk factor (HCV, alcohol or non-alcoholic steato-hepatitis, p=0.006). P53 was the most frequently altered pathway in HBV-related HCC (47%, p=0.001). Furthermore, TP53 mutations were associated with shorter survival only in HBV-related HCC (p=0.02) whereas R249S mutations were identified exclusively in migrants. Compared with other aetiologies, HBV-HCC were more frequently classified in tumours subgroups with upregulation of genes involved in cell-cycle regulation and a progenitor phenotype. Finally, in HBV-related HCC, transcriptomic profiles were associated with specific gene mutations (HBX, TP53, IRF2, AXIN1 and CTNNB1). Conclusions Integrated genomic characterisation of HBV and non-HBV-related HCC emphasised the immense molecular diversity of HCC closely related to aetiologies that could impact clinical care of HCC patients. PMID:25021421

  7. Sleeping Beauty transposon-based system for rapid generation of HBV-replicating stable cell lines.

    PubMed

    Wu, Yong; Zhang, Tian-Ying; Fang, Lin-Lin; Chen, Zi-Xuan; Song, Liu-Wei; Cao, Jia-Li; Yang, Lin; Yuan, Quan; Xia, Ning-Shao

    2016-08-01

    The stable HBV-replicating cell lines, which carry replication-competent HBV genome stably integrated into the genome of host cell, are widely used to evaluate the effects of antiviral agents. However, current methods to generate HBV-replicating cell lines, which are mostly dependent on random integration of foreign DNA via plasmid transfection, are less-efficient and time-consuming. To address this issue, we constructed an all-in-one Sleeping Beauty transposon system (denoted pTSMP-HBV vector) for robust generation of stable cell lines carrying replication-competent HBV genome of different genotype. This vector contains a Sleeping Beauty transposon containing HBV 1.3-copy genome with an expression cassette of the SV40 promoter driving red fluorescent protein (mCherry) and self-cleaving P2A peptide linked puromycin resistance gene (PuroR). In addition, a PGK promoter-driven SB100X hyperactive transposase cassette is placed in the outside of the transposon in the same plasmid.The HBV-replicating stable cells could be obtained from pTSMP-HBV transfected HepG2 cells by red fluorescence-activated cell sorting and puromycin resistant cell selection within 4-week. Using this system, we successfully constructed four cell lines carrying replication-competent HBV genome of genotypes A-D. The replication and viral protein expression profiles of these cells were systematically characterized. In conclusion, our study provides a high-efficiency strategy to generate HBV-replicating stable cell lines, which may facilitate HBV-related virological study. PMID:27091097

  8. Reactive oxygen species promote heat shock protein 90-mediated HBV capsid assembly

    SciTech Connect

    Kim, Yoon Sik Seo, Hyun Wook Jung, Guhung

    2015-02-13

    Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. - Highlights: • We examined H{sub 2}O{sub 2} and GSH modulate HBV capsid assembly. • H{sub 2}O{sub 2} facilitates HBV capsid assembly in the presence of Hsp90. • GSH inhibits function of Hsp90 in facilitating HBV capsid assembly. • H{sub 2}O{sub 2} and GSH induce conformation change of Hsp90.

  9. Molecular characterization of hepatitis B virus (HBV) isolates, including identification of a novel recombinant, in patients with acute HBV infection attending an Irish hospital.

    PubMed

    Laoi, Bairbre Ni; Crowley, B

    2008-09-01

    Hepatitis B virus (HBV) is known to show significant genetic diversity. There are eight HBV genotypes (A-H) characterized by distinct geographical distribution. Mutations in the HBV genome, in particular precore (PC) and basal core promoter (BCP) mutations, may be important factors in the pathogenesis of disease. In this study genetic heterogeneity and phylogenetic analysis of HBV isolates from 32 naïve patients with acute HBV infection was investigated. Eleven patients presented with severe infection, while the remaining 21 had self-limiting illness. Only four isolates from patients with severe HBV infection harbored the G1896A stop codon mutation. One isolate (Irish-13), collected from a patient with acute asymptomatic infection, had a G1896A mutation and a 243 bp deletion of the polymerase gene. A triple mutation, T1753C/A1762T/G1764A was identified in only one isolate (Irish-3) associated with severe infection. The latter also had a mutation, A2339G, in the core gene, not previously reported in severe acute infection caused by genotype D. Variations within the S gene were identified in 6 isolates, including Gly145Ala, associated with vaccine immune escape, Asp144Glu, Ser143Leu and Phe134Leu, each associated with failure to detect HBsAg. Phylogenetic analysis was determined using amplicons of the S gene (678 bp) and distal-X/PC region (672 bp). Genotype A was the most common (75%), followed by genotype D (15.6%), and equal proportions of C, E, F, and H. A novel recombinant of genotypes D and E was identified in an isolate originating from West Africa. Genetic heterogeneity of HBV isolates of HBV isolates from patients with acute infection needs further study of its significance. PMID:18649329

  10. Design, synthesis, molecular docking studies and anti-HBV activity of phenylpropanoid derivatives.

    PubMed

    Liu, Sheng; Li, Yubin; Wei, Wanxing; Wang, Kuiwu; Wang, Lisheng; Wang, Jianyi

    2016-05-01

    In this work, a series of phenylpropanoid derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated. Most of the synthesized derivatives showed effective anti-HBV activity. And compound 4d-3 showed the most effective anti-HBV activity, performing strong potent inhibitory not only on the secretion of HBsAg (IC50 = 58.28 μM, SI = 23.26) and HBeAg (IC50 = 97.21 μM, SI = 13.95), but also on the HBV DNA replication (IC50 = 42.28 μM, SI = 32.06). The structure-activity relationships (SARs) of the derivatives had been discussed, which were useful for developing phenylpropanoid derivatives as novel anti-HBV agents. Moreover, the docking study of all synthesized compounds inside the HLA-A protein (PDB ID: 3OX8) active site was carried out to explore the molecular interactions and a molecular target for activity and a modified assay method measuring the interaction between our derivatives and HBcAg was investigated, indicating that the HBV core protein might be their potential target for anti-HBV. This study identified a new class of potent non-nucleoside anti-HBV agents. PMID:26980103

  11. Injecting and sexual risk correlates of HBV and HCV seroprevalence among new drug injectors

    PubMed Central

    Neaigus, Alan; Gyarmathy, V. Anna; Miller, Maureen; Frajzyngier, Veronica M.; Zhao, Mingfang; Friedman, Samuel R.; Des Jarlais, Don C.

    2007-01-01

    We examine injecting and sexual risk correlates of hepatitis B (HBV) and hepatitis C (HCV) seroprevalence among new injecting drug users (IDUs) (age 18–30 years, injecting ≤6 years). Participants were interviewed/serotested (HIVab, HBVcAb, HCVab) in New York City, 2/1999–2/2003. Gender-stratified, multivariate logistic regression was conducted. Participants (N=259) were: 68% male; 81% white. Women were more likely to test HCV seropositive (42% vs. 27%) and men HBV seropositive (24% vs. 12%); HIV seroprevalence was low (3%). Among both men and women, HBV seropositivity was associated with ever selling sex, and HCV seropositivity with ever having had infected (HIV, HBV or HCV) sex partners (among those ever sharing injecting equipment). Among women only, HBV seropositivity was associated with ever having had infected sex partners (regardless of ever sharing injecting equipment), and HCV seropositivity with ≥300 lifetime drug injections. Among men only, HCV seropositivity was associated with ≥40 lifetime number of sex partners (among those never sharing injecting equipment). In this new IDU sample, HBV and HCV seroprevalence differed by gender and were considerably higher than HIV seroprevalence. Early interventions, targeting injecting and sexual risks and including HBV vaccination, are needed among new IDUs to prevent HBV, HCV and, potentially, HIV epidemics. PMID:17289298

  12. Genomic responses to hepatitis B virus (HBV) infection in primary human hepatocytes

    PubMed Central

    Ancey, Pierre-Benoit; Testoni, Barbara; Gruffaz, Marion; Cros, Marie-Pierre; Durand, Geoffroy; Le Calvez-Kelm, Florence; Durantel, David; Herceg, Zdenko; Hernandez-Vargas, Hector

    2015-01-01

    Viral infections are able to modify the host's cellular programs, with DNA methylation being a biological intermediate in this process. The extent to which viral infections deregulate gene expression and DNA methylation is not fully understood. In the case of Hepatitis B virus (HBV), there is evidence for an interaction between viral proteins and the host DNA methylation machinery. We studied the ability of HBV to modify the host transcriptome and methylome, using naturally infected primary human hepatocytes to better mimic the clinical setting. Gene expression was especially sensitive to culture conditions, independently of HBV infection. However, we identified non-random changes in gene expression and DNA methylation occurring specifically upon HBV infection. There was little correlation between expression and methylation changes, with transcriptome being a more sensitive marker of time-dependent changes induced by HBV. In contrast, a set of differentially methylated sites appeared early and were stable across the time course experiment. Finally, HBV-induced DNA methylation changes were defined by a specific chromatin context characterized by CpG-poor regions outside of gene promoters. These data support the ability of HBV to modulate host cell expression and methylation programs. In addition, it may serve as a reference for studies addressing the genome-wide consequences of HBV infection in human hepatocytes. PMID:26565721

  13. Reactive oxygen species promote heat shock protein 90-mediated HBV capsid assembly.

    PubMed

    Kim, Yoon Sik; Seo, Hyun Wook; Jung, Guhung

    2015-02-13

    Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. PMID:25576869

  14. Construction of the HBV S-ecdCD40L fusion gene and effects of HBV S-ecdCD40L modification on function of dendritic cells.

    PubMed

    Wu, J-M; Lin, X-F; Huang, Z-M; Wu, J S

    2011-10-01

    We examined the effect of dendritic cells engineered to express an HBV S antigen CD40L fusion gene (HBV S-ecdCD40L). The DNA of HBV S gene and the cDNA of the extracellular domain of human CD40 ligand were linked by cloning. Peripheral blood mononuclear cells (PBMC) from healthy adults were incubated and induced into dendritic cells (DC) in presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4(IL-4). The DCs were transfected the novel construct, and the impact of the expressed clone assessed. We find that, compared with control groups, modification of DCs with HBV S-ecdCD40L fusion gene resulted in the activation of DCs with upregulated expression of immunologically important cell surface molecules (CD80, CD86 and HLA-DR) and proinflammatory cytokines (IL-12). The DCs modified with HBV S-ecdCD40L are able to stimulate enhanced allogeneic T-cell proliferation in vitro. Thus, the fusion gene HBV S-ecdCD40L can promote DC's activation and enhance its function and may prove to be the foundation for a new type of hepatitis B vaccine. PMID:21914064

  15. Actual and perceived HBV status among Asian Pacific Islander Americans in Rhode Island: a cross-sectional study.

    PubMed

    Ha, Austin Y; Nguyen, Joyce E; Doyle, Richard J; Feller, Edward

    2015-05-01

    Chronic hepatitis B (HBV) in the Asian and Pacific Islander (API) American population is an under-recognized health issue in the United States. Among foreign-born API, the prevalence of HBV is approximately 10%. The prevalence in the general population is below 0.5%; among non-Hispanic whites it is below 0.2%. We examined beliefs held by the API populations in Rhode Island (RI) about personal HBV status and compared them with their actual HBV status. Of 59 total study participants, only 19 (32%) participants correctly knew their HBV status. Six (10%) participants were carriers of HBV; 18 (31%) lacked immunity to the virus. This pilot study suggests the RI API population is not knowledgeable about their own HBV status and are inadequately screened, vaccinated against, and treated for HBV. Increased statewide screening and education efforts, tailored to address this population, are needed to identify and inform those in need of medical attention or vaccination. PMID:25938399

  16. NIRF, a Novel Ubiquitin Ligase, Inhibits Hepatitis B Virus Replication Through Effect on HBV Core Protein and H3 Histones.

    PubMed

    Qian, Guanhua; Hu, Bin; Zhou, Danlin; Xuan, Yanyan; Bai, Lu; Duan, Changzhu

    2015-05-01

    Np95/ICBP90-like RING finger protein (NIRF), a novel E3 ubiquitin ligase, has been shown to interact with HBc and promote its degradation. This study investigated the effects of NIRF on replication of hepatitis B virus (HBV) and the mechanisms. We have shown that NIRF inhibits replication of HBV DNA and secretion of HBsAg and HBeAg in HepG2 cells transfected with pAAV-HBV1.3. NIRF also inhibits the replication and secretion of HBV in a mouse model that expressed HBV. NIRF reduces acetylation of HBV cccDNA-bound H3 histones. These results showed that NIRF is involved in the HBV replication cycle not only through direct interaction with HBc but also reduces acetylation of HBV cccDNA-bound H3 histones. PMID:25664994

  17. Proteomics Based Identification of Cell Migration Related Proteins in HBV Expressing HepG2 Cells

    PubMed Central

    Feng, Huixing; Li, Xi; Chan, Vincent; Chen, Wei Ning

    2014-01-01

    Proteomics study was performed to investigate the specific protein expression profiles of HepG2 cells transfected with mutant HBV compared with wildtype HBV genome, aiming to identify the specific functions of SH3 binding domain (proline rich region) located in HBx. In addition to the cell movement and kinetics changes due to the expression of HBV genome we have observed previously, here we further targeted to explore the specific changes of cellular proteins and potential intracellular protein interactions, which might provide more information of the potential cellular mechanism of the differentiated cell movements. Specific changes of a number of proteins were shown in global protein profiling in HepG2 cells expressing wildtype HBV, including cell migration related proteins, and interestingly the changes were found recovered by SH3 binding domain mutated HBV. The distinctive expressions of proteins were validated by Western blot analysis. PMID:24763314

  18. Dynamics of an HBV Model with Drug Resistance Under Intermittent Antiviral Therapy

    NASA Astrophysics Data System (ADS)

    Zhang, Ben-Gong; Tanaka, Gouhei; Aihara, Kazuyuki; Honda, Masao; Kaneko, Shuichi; Chen, Luonan

    2015-06-01

    This paper studies the dynamics of the hepatitis B virus (HBV) model and the therapy regimens of HBV disease. First, we propose a new mathematical model of HBV with drug resistance, and then analyze its qualitative and dynamical properties. Combining the clinical data and theoretical analysis, we demonstrate that our model is biologically plausible and also computationally viable. Second, we demonstrate that the intermittent antiviral therapy regimen is one of the possible strategies to treat this kind of complex disease. There are two main advantages of this regimen, i.e. it not only may delay the development of drug resistance, but also may reduce the duration of on-treatment time compared with the long-term continuous medication. Moreover, such an intermittent antiviral therapy can reduce the adverse side effects. Our theoretical model and computational results provide qualitative insight into the progression of HBV, and also a possible new therapy for HBV disease.

  19. Branched oligosaccharide structures on HBV prevent interaction with both DC-SIGN and L-SIGN.

    PubMed

    Op den Brouw, M L; de Jong, M A W P; Ludwig, I S; van der Molen, R G; Janssen, H L A; Geijtenbeek, T B H; Woltman, A M

    2008-09-01

    Hepatitis B virus (HBV) is a DNA virus that infects the liver as primary target. Currently, a high affinity receptor for HBV is still unknown. The dendritic cell specific C-type lectin DC-SIGN is involved in pathogen recognition through mannose and fucose containing carbohydrates leading to the induction of an anti-viral immune response. Many glycosylated viruses subvert this immune surveillance function and exploit DC-SIGN as a port of entry and for trans-infection of target cells. The glycosylation pattern on HBV surface antigens (HBsAg) together with the tissue distribution of HBV would allow interaction between HBV and DC-SIGN and its liver-expressed homologue L-SIGN. Therefore, a detailed study to investigate the binding of HBV to DC-SIGN and L-SIGN was performed. For HCV, both DC-SIGN and L-SIGN are known to bind envelope glycoproteins E1 and E2. Soluble DC-SIGN and L-SIGN specifically bound HCV virus-like particles, but no interaction with either HBsAg or HepG2.2.15-derived HBV was detected. Also, neither DC-SIGN nor L-SIGN transfected Raji cells bound HBsAg. In contrast, highly mannosylated HBV, obtained by treating HBV producing HepG2.2.15 cells with the alpha-mannosidase I inhibitor kifunensine, is recognized by DC-SIGN. The alpha-mannosidase I trimming of N-linked oligosaccharide structures thus prevents recognition by DC-SIGN. On the basis of these findings, it is tempting to speculate that HBV exploits mannose trimming as a way to escape recognition by DC-SIGN and thereby subvert a possible immune activation response. PMID:18482282

  20. Distribution and Epidemiologic Trends of HBV Genotypes and Subtypes in 14 Countries Neighboring China

    PubMed Central

    Qian, Zhao; Jianqiong, Wang; Hongmei, Li; Rong, Zeng; Li, Li; Jinping, Zhang; Tao, Shen

    2015-01-01

    Background: The number of cases of HBV infection reported by the WHO for each district and country is positively correlated with the number of HBV sequences in the database isolated from the corresponding district and country. Objectives: This study determined distribution characteristics of HBV genotypes and subtypes in 14 countries neighboring China. The progress made in genomic research involving HBV was also reviewed. Materials and Methods: Nine hundred fifty-one complete genome sequences of HBV from 14 countries neighboring China were selected from NCBI. The sequence-related information was analyzed and recorded. One hundred seventy-two sequences of HBV genotype B were screened for alignment using DNA star and MEGA 5.1. Results: Dominant HBV genotypes in the countries neighboring China were genotypes B, C and D and dominant subtypes were adw2 and adrq+. The association between genotype and serotype of HBV in these countries was shown to differ from previous research results. As shown by sequence alignment, the sequence divergence between five subgenotypes (B3, B5, B7, B8 and B9) was below 4%. The B subgenotypes shared six common specific amino acid sites in the S region. Conclusions: The B3, B5, B7, B8 and B9 subgenotypes can be clustered into quasi-sub-genotype B3 and the open reading frame of HBV has a start codon preference; however, whether a mutation in the start codon in the pre-S2 region has an impact on survival and replication of HBV remains to be determined. PMID:26045702

  1. Expanding motion in the ionized envelope of HBV 475

    SciTech Connect

    Tamura, S.

    1981-01-01

    Expansion velocities in the ionized envelope of HBV 475 are obtained from line profiles of H-alpha, He I 6678, 7065, and forbidden Fe VII 6087. Two components of forbidden Fe VII 6087 show evidence of outward gas motion with high velocities from the central star. H-alpha and He I 6678 profiles are very similar to those obtained from observations of forbidden O III and Ne III lines, and have gas motion velocities corresponding to full widths at half-maximum of the lines which do not exceed the velocities of Fe(+6). Through investigations of He(+) and Fe(+5) ionization structures, it is concluded that the interacting stellar winds model is favorable to explain the velocity fields suggested by the line profiles.

  2. Association between interleukin-21 gene polymorphisms (rs12508721) and HBV-related hepatocellular carcinoma.

    PubMed

    Zhang, Q X; Li, S L; Yao, Y Q; Li, T J

    2016-06-01

    Interleukin-21 (IL-21), as a multifunctional cytokine, plays an important role in many diseases, such as cancer, inflammatory and autoimmune diseases. We aimed to investigate the relationship between polymorphisms of IL-21 gene and susceptibility of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in a Chinese population. Studied subjects were divided into three groups: 100 patients with HBV-related HCC, 115 patients with chronic HBV infection and 127 healthy controls. Genomic DNA was isolated from peripheral blood, and the polymerase chain reaction-ligase detection reaction (PCR-LDR) method was used to genotype the SNPs (rs2221903, rs907715 and rs12508721) within IL-21 gene. Our results showed that IL-21 polymorphisms were associated with the risk of HCC and chronic HBV infection when compared with healthy controls. The rs2221903A/G AG genotype was associated with a higher risk of chronic HBV infection when compared with healthy controls [AG versus AA + GG, P = 0.036, OR = 1.898, 95%CI = 1.038-3.471]. The rs12508721C/T TT genotype was related with a lower risk of chronic HBV infection and HBV-related HCC than in healthy controls [TT versus CT + CC, P = 0.026, OR = 0.451, 95%CI = 0.221-0.920; P = 0.049, OR = 0.482, 95%CI = 0.231-1.005]. No significant difference in the genotype and allele distrubutions of rs907715G/A SNP was observed in the HBV-related HCC group, chronic HBV-infected group and the healthy control group when compared to each other. Our findings suggest that the rs12508721T/C and rs2221903A/G polymorphisms of IL-21 gene are associated with the susceptibility of HBV-related HCC and chronic HBV infection. The genetic variant may in fact cause protection against the HBV-related HCC. However, the function in these SNPs of IL-21 gene needs to clarify the mechanisms involved in the pathogenesis of HBV-related HCC further. PMID:27122304

  3. Hepatitis B virus (HBV) receptors: Deficiency in tumor results in scant HBV infection and overexpression in peritumor leads to higher recurrence risk

    PubMed Central

    Ye, Fei; Fan, Qing-Min; Yu, Guo-Feng; Yu, Dan-Dan; Gao, Lu; Sun, Kai; Han, Zhi-Peng; Li, Rong; Yang, Yang; Zhao, Qiu-Dong; Wu, Meng-Chao; Wang, Hong-Yang; Wei, Li-Xin

    2015-01-01

    Hepatitis B virus (HBV) infection is a risk factor for hepatocarcinogenesis and recurrence. Here, we sought to characterize intratumoral and peritumoral expression of HBsAg and its specific receptors in HBsAg-positive hepatocellular carcinoma (HCC) patients and further examined their correlation with the recurrence-free survival (RFS). HCC tissue and adjacent normal tissue specimens were acquired from HBsAg-positive patients. The presence of HBsAg and receptors, as well as hepatic progenitor cells (HPCs) were detected by tissue microassay and immunohistochemistry. Necroinflammatory activity was evaluated by HE staining. The mean IOD of HBsAg and HBV DNA in the intratumoral tissues was markedly lower than that in the peritumoral tissues (P < 0.001). Pearson correlation analysis further showed a significant correlation between the expression of HBsAg and NTCP (r = 0.461, P < 0.001) or ASGPR (r = 0.506, P < 0.001) in peritumoral tissues. And the peritumoral HBsAg and receptors presented a positive association with necroinflammatory activity (P < 0.05). Inflammation induced by HBV infection presented a positive association with HPCs activation (P < 0.05). Additionally, due to lack of HBV receptors, HPCs was not preferentially infected with HBV, but activated HPCs had a significant correlation with HBsAg expression in peritumoral tissues, and the peritumoral HPCs activation was associated with RFS of HCC patients, therefore, the overexpression of HBsAg and receptors in peritumor were also with higher recurrence risk (P < 0.05). In conclusion, lack of HBV receptors resulted in scant HBV infection in tumor cells, and overexpression of HBsAg and receptors in peritumor was strongly associated with higher recurrence risk in HCC patients. PMID:26515593

  4. Association of an HLA-G 14-bp Insertion/Deletion polymorphism with high HBV replication in chronic hepatitis.

    PubMed

    Laaribi, A B; Zidi, I; Hannachi, N; Ben Yahia, H; Chaouch, H; Bortolotti, D; Zidi, N; Letaief, A; Yacoub, S; Boudabous, A; Rizzo, R; Boukadida, J

    2015-10-01

    Identification of an HLA-G 14-bp Insertion/Deletion (Ins/Del) polymorphism at the 3' untranslated region of HLA-G revealed its importance in HLA-G mRNA stability and HLA-G protein level variation. We evaluated the association between the HLA-G 14-bp Ins/Del polymorphism in patients with chronic Hepatitis B virus (HBV) infection in a case-control study. Genomic DNA was extracted from 263 patients with chronic HBV hepatitis and 246 control subjects and was examined for the HLA-G 14-bp Ins/Del polymorphism by PCR. The polymorphic variants were genotyped in chronic HBV seropositive cases stratified according to HBV DNA levels, fibrosis stages and in a control population. There was no statistical significant association between the 14-bp Ins/Del polymorphism and increased susceptibility to HBV infection neither for alleles (P = 0.09) nor for genotypes (P = 0.18). The stratification of HBV patients based on HBV DNA levels revealed an association between the 14-bp Ins/Del polymorphism and an enhanced HBV activity with high HBV DNA levels. In particular, the Ins allele was significantly associated with high HBV DNA levels (P = 0.0024, OR = 1.71, 95% CI 1.2-2.4). The genotype Ins/Ins was associated with a 2.5-fold (95% CI, 1.29-4.88) increased risk of susceptibility to high HBV replication compared with the Del/Del and Ins/Del genotypes. This susceptibility is linked to the presence of two Ins alleles. No association was observed between the 14-bp Ins/Del polymorphism and fibrosis stage of HBV infection. We observed an association between the 14-bp Ins/Del polymorphism and high HBV replication characterized by high HBV DNA levels in chronic HBV patients. These results suggest a potential prognostic value for disease outcome evaluation. PMID:25619305

  5. ProMat

    Energy Science and Technology Software Center (ESTSC)

    2008-06-12

    ProMAT is a software tool for statistically analyzing data from enzyme-linked immunosorbent assay microarray experiments. The software estimates standard curves, sample protein concentrations and their uncertainties for multiple assays. ProMAT generates a set of comprehensive figures for assessing results and diagnosing process quality. The tool is available for Windows or Mac, and is distributed as open-source Java and R code

  6. Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice

    PubMed Central

    Shih, Yao-Ming; Sun, Cheng-Pu; Chou, Hui-Hsien; Wu, Tzu-Hui; Chen, Chun-Chi; Wu, Ping-Yi; Enya Chen, Yu-Chen; Bissig, Karl-Dimiter; Tao, Mi-Hua

    2015-01-01

    Selection of escape mutants with mutations within the target sequence could abolish the antiviral RNA interference activity. Here, we investigated the impact of a pre-existing shRNA-resistant HBV variant on the efficacy of shRNA therapy. We previously identified a highly potent shRNA, S1, which, when delivered by an adeno-associated viral vector, effectively inhibits HBV replication in HBV transgenic mice. We applied the “PICKY” software to systemically screen the HBV genome, then used hydrodynamic transfection and HBV transgenic mice to identify additional six highly potent shRNAs. Human liver chimeric mice were infected with a mixture of wild-type and T472C HBV, a S1-resistant HBV variant, and then treated with a single or combined shRNAs. The presence of T472C mutant compromised the therapeutic efficacy of S1 and resulted in replacement of serum wild-type HBV by T472C HBV. In contrast, combinatorial therapy using S1 and P28, one of six potent shRNAs, markedly reduced titers for both wild-type and T472C HBV. Interestingly, treatment with P28 alone led to the emergence of escape mutants with mutations in the P28 target region. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients. PMID:26482836

  7. HBV lamivudine resistance among hepatitis B and HIV coinfected patients starting lamivudine, stavudine and nevirapine in Kenya.

    PubMed

    Kim, H N; Scott, J; Cent, A; Cook, L; Morrow, R A; Richardson, B; Tapia, K; Jerome, K R; Lule, G; John-Stewart, G; Chung, M H

    2011-10-01

    Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV-HBV coinfected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV-infected adults before and for 18 months after starting highly active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty-seven (6.9%) were HBsAg positive and anti-HBs negative, 24 were HBeAg negative, and 18 had HBV DNA levels ≤ 10,000 IU/mL. Sustained HBV suppression to <100 IU/mL occurred in 89% of 19 evaluable patients. Resistance occurred in only two subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV-HBV coinfected patients with low baseline HBV DNA levels. PMID:21914062

  8. Chronic hepatitis B infection and HBV DNA-containing capsids: Modeling and analysis

    NASA Astrophysics Data System (ADS)

    Manna, Kalyan; Chakrabarty, Siddhartha P.

    2015-05-01

    We analyze the dynamics of chronic HBV infection taking into account both uninfected and infected hepatocytes along with the intracellular HBV DNA-containing capsids and the virions. While previous HBV models have included either the uninfected hepatocytes or the intracellular HBV DNA-containing capsids, our model accounts for both these two populations. We prove the conditions for local and global stability of both the uninfected and infected steady states in terms of the basic reproduction number. Further, we incorporate a time lag in the model to encompass the intracellular delay in the production of the infected hepatocytes and find that this delay does not affect the overall dynamics of the system. The results for the model and the delay model are finally numerically illustrated.

  9. Sorafenib Combined With Transarterial Chemoembolization in Treating HBV-infected Patients With Intermediate Hepatocellular Carcinoma

    ClinicalTrials.gov

    2012-04-24

    PHENYTOIN/SORAFENIB [VA Drug Interaction]; Liver Neoplasms; Carcinoma, Hepatocellular; Digestive System Neoplasms; Neoplasms by Site; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; DOXORUBICIN/TRASTUZUMAB [VA Drug Interaction]; HBV

  10. Know HBV: What Every Asian and Pacific Islander Should Know About Hepatitis B and Liver Cancer

    MedlinePlus

    ... the skin or eyes) appear, it is often too late for treatment to be effective. » T ransmitted just like HIV 1. A mother-to-child infection For Asians, HBV is commonly transmitted from a chronically infected ...

  11. Basis of HBV persistence and new treatment options.

    PubMed

    Thursz, Mark

    2014-09-01

    The majority of the morbidity and mortality associated with hepatitis B virus infection is due to viral persistence and its consequences. The heterogeneity of outcomes from HBV infection suggests that both viral and host factors influence the development of chronic infection. Study of host genetic susceptibility has revealed a number of genes including MHC class II loci and cytokine receptors, which decrease the risk of persistence. On the viral side, the replication system is adapted to generate high levels of virions without stimulating the innate immune system. Secreted viral proteins (HBsAg and HBeAg) suppress innate responses through inhibition of TLR signaling, which leads to a weak adaptive immune response with an exhausted phenotype that is incapable of inducing viral elimination. However, even when the adaptive immune system begins to take effect after HBe seroconversion, the ability of the virus to mutate and evade T and B cell-mediated responses helps to sustain persistent infection. Understanding the mechanisms of persistence is important for the design of therapeutic strategies. Although there are currently no specific drugs that target the viral minichromosome (cccDNA), it is expected that in the future we will be able to use existing drugs more effectively to eliminate the infection. PMID:26201329

  12. Establishment of drug-resistant HBV small-animal models by hydrodynamic injection

    PubMed Central

    Cheng, Junjun; Han, Yanxing; Jiang, Jian-Dong

    2014-01-01

    In antiviral therapy of hepatitis B virus (HBV) infection, drug resistance remains a huge obstacle to the long-term effectiveness of nucleoside/tide analogs (NAs). Primary resistance mutation (rtM204V) contributes to lamivudine (LAM)-resistance, and compensatory mutations (rtL180M and rtV173L) restore viral fitness and increase replication efficiency. The evaluation of new anti-viral agents against drug-resistant HBV is limited by the lack of available small-animal models. We established LAM-resistance HBV replication mice models based on clinical LAM-resistant HBV mutants. Double (rtM204V+rtL180M) or triple (rtM204V+rtL180M+rtV173L) lamivudine-resistant mutations were introduced into HBV expression vector, followed by hydrodynamic injection into tail vein of NOD/SCID mice. Viremia was detected on days 5, 9, 13 and 17 and liver HBV DNA was detected on day 17 after injection. The serum and liver HBV DNA levels in LAM-resistant model carrying triple mutations are the highest among the models. Two NAs, LAM and entecavir (ETV), were used to test the availability of the models. LAM and ETV inhibited viral replication on wild-type model. LAM was no longer effective on LAM-resistant models, but ETV retains a strong activity. Therefore, these models can be used to evaluate anti-viral agents against lamivudine-resistance, affording new opportunities to establish other drug-resistant HBV small-animal models. PMID:26579395

  13. The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion

    PubMed Central

    Chou, Shu-Fan; Tsai, Ming-Lin; Huang, Jyun-Yuan; Chang, Ya-Shu; Shih, Chiaho

    2015-01-01

    The Endosomal Sorting Complex Required for Transport (ESCRT) is an important cellular machinery for the sorting and trafficking of ubiquitinated cargos. It is also known that ESCRT is required for the egress of a number of viruses. To investigate the relationship between ESCRT and hepatitis B virus (HBV), we conducted an siRNA screening of ESCRT components for their potential effect on HBV replication and virion release. We identified a number of ESCRT factors required for HBV replication, and focused our study here on HGS (HRS, hepatocyte growth factor-regulated tyrosine kinase substrate) in the ESCRT-0 complex. Aberrant levels of HGS suppressed HBV transcription, replication and virion secretion. Hydrodynamic delivery of HGS in a mouse model significantly suppressed viral replication in the liver and virion secretion in the serum. Surprisingly, overexpression of HGS stimulated the release of HBV naked capsids, irrespective of their viral RNA, DNA, or empty contents. Mutant core protein (HBc 1–147) containing no arginine-rich domain (ARD) failed to secrete empty virions with or without HGS. In contrast, empty naked capsids of HBc 1–147 could still be promoted for secretion by HGS. HGS exerted a strong positive effect on the secretion of naked capsids, at the expense of a reduced level of virions. The association between HGS and HBc appears to be ubiquitin-independent. Furthermore, HBc is preferentially co-localized with HGS near the cell periphery, instead of near the punctate endosomes in the cytoplasm. In summary, our work demonstrated the importance of an optimum level of HGS in HBV propagation. In addition to an effect on HBV transcription, HGS can diminish the pool size of intracellular nucleocapsids with ongoing genome maturation, probably in part by promoting the secretion of naked capsids. The secretion routes of HBV virions and naked capsids can be clearly distinguished based on the pleiotropic effect of HGS involved in the ESCRT-0 complex. PMID

  14. Co-infection assessment in HBV, HCV, and HIV patients in Western Saudi Arabia.

    PubMed

    Al-Mughales, Jamil A

    2016-09-01

    To estimate the prevalence of diagnosed and undiagnosed coinfections among HIV, HBV, and HCV infected patients. Retrospective analysis of laboratory records for HIV, HBV, and HCV patients presenting at the HIV outpatient clinic. Serological data including hepatitis B surface antigen (HBsAg), hepatitis B e-antigen (HBeAg), hepatitis B e-antibody (anti-HBe), antibodies to HIV and HCV, anti-toxoplasmosis IgG and IgM antibodies, and anti-syphilis antibodies (VDRL) were collected. We obtained data for 628 (218 HCV, 268 HBV, and 142 HIV) patients. Male-to-female ratios were 1:1 for HCV, 3:4 for HBV, and 5:3 for HIV. Age means (SD) were 54.24 (16.40), 44.53 (18.83), and 40.39 (15.92) years for HCV, HBV, and HIV, respectively. In HIV group, the prevalence of HBV and HCV coinfections was 8.5% and 2.8%, respectively. In HBV group, the prevalence of HCV and HIV coinfections was 1.1% and 1.5%, respectively. In HCV group, HIV or HBV coinfections occurred at the same frequency (1.4%). An absence of screening for coinfections was detected in 7.0-48.5% patients as per the group and the infectious agent; which represents an estimated proportion of 20 out of 1,000 patients with an undiagnosed coinfection. Despite a relatively low prevalence of coinfections, a significant proportion of cases remain undiagnosed because of a lack of systematic screening. J. Med. Virol. 88:1545-1551, 2016. © 2016 Wiley Periodicals, Inc. PMID:26895691

  15. Cortical signature of patients with HBV-related cirrhosis without overt hepatic encephalopathy: a morphometric analysis.

    PubMed

    Wu, Xiu; Lv, Xiao-Fei; Zhang, Yu-Ling; Wu, Hua-Wang; Cai, Pei-Qiang; Qiu, Ying-Wei; Zhang, Xue-Lin; Jiang, Gui-Hua

    2015-01-01

    Previous studies have shown that patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt hepatic encephalopathy (OHE) are associated with a varying degree of cognitive dysfunction. Several resting-state functional magnetic resonance imaging (fMRI) studies have been conducted to explore the neural correlates of such cognitive deficits, whereas little effort has been made to investigate the cortical integrity in cirrhotic patients without OHE. Here, using cortical thickness, surface area and local gyrification index (lGI), this study performed a comprehensive analysis on the cortical morphometry of patients with HBV-RC without OHE (HBV-RC-NOHE) vs. matched healthy controls. Compared with healthy controls, we found significantly increased cortical thickness in the bilateral lingual and parahippocampal gyrus, right posterior cingulate cortex, precuneus, peri-calcarine sulcus and fusiform gyrus in patient with HBV-RC-NOHE, which may closely relate to be the low-grade brain edema. Cortical gyrification analysis showed significantly increased lGI in the left superior and inferior parietal cortex as well as lateral occipital cortex, which was speculated to be associated with disruptions in white matter connectivity and sub-optimal intra-cortical organization. In addition, the mean cortical thickness/lGI of the regions with structural abnormalities was shown to be negatively correlated with psychometric hepatic encephalopathy score (PHES) of the patients with HBV-RC-NOHE. These morphological changes may serve as potential markers for the preclinical diagnosis and progression of HBV-RC-NOHE. PMID:26106307

  16. Pediatric HIV-HBV Coinfection in Lusaka, Zambia: Prevalence and Short-Term Treatment Outcomes.

    PubMed

    Peebles, Kathryn; Nchimba, Lweendo; Chilengi, Roma; Bolton Moore, Carolyn; Mubiana-Mbewe, Mwangelwa; Vinikoor, Michael J

    2015-12-01

    Hepatitis B virus (HBV) is endemic in Africa, where it may occur as an HIV coinfection. Data remain limited on HIV-HBV epidemiology in Africa, particularly in children. Using programmatic data from pediatric HIV clinics in Lusaka, Zambia during 2011-2014, we analyzed the prevalence of chronic HBV coinfection (defined as a single positive hepatitis B surface antigen [HBsAg] test) and its impact on immune recovery and liver enzyme elevation (LEE) during the first year of antiretroviral therapy. Among 411 children and adolescents, 10.4% (95% confidence interval, 7.6-14.1) had HIV-HBV. Coinfected patients were more likely to have World Health Organization stage 3/4, LEE and CD4 <14% at care entry (all p < 0.05). During treatment, CD4 increases and LEE incidence were similar by HBsAg status. HBsAg positivity decreased (11.8% vs. 6.6%; p = 0.24) following HBV vaccine introduction. These findings support screening pediatric HIV patients in Africa for HBV coinfection. Dedicated cohorts are needed to assess long-term outcomes of coinfection. PMID:26338421

  17. Discovering novel direct acting antiviral agents for HBV using in silico screening.

    PubMed

    Murakami, Yoshiki; Hayakawa, Michiyo; Yano, Yoshihiko; Tanahashi, Toshihito; Enomoto, Masaru; Tamori, Akihiro; Kawada, Norifumi; Iwadate, Mitsuo; Umeyama, Hideaki

    2015-01-01

    The treatments for chronic hepatitis B (CHB) are interferon and nucleoside analogues reverse transcriptase (RT) inhibitors. Because both treatments are less than ideal, we conducted to identify novel anti-viral agents for HBV-reverse transcriptase (HBV-RT). We determined the ligand-binding site of the HBV-RT by conducting a homological search of the amino acid sequence and then we also determined not only structural arrangement of the target protein but the target protein-binding site of the ligand using known protein-ligand complexes in registered in the protein data bank (PDB). Finally we simulated binding between the ligand candidates and the HBV-RT and evaluated the degree of binding (in silico screening). PXB cells derived from human-mouse chimeric mouse liver, infected with HBV were administrated with the candidates, and HBVDNA in the culture medium was monitored by realtime qPCR. Among compounds from the AKosSamples database, twelve candidates that can inhibit RT were also identified, two of which seem to have the potential to control HBV replication in vitro. PMID:25446116

  18. Cortical signature of patients with HBV-related cirrhosis without overt hepatic encephalopathy: a morphometric analysis

    PubMed Central

    Wu, Xiu; Lv, Xiao-Fei; Zhang, Yu-Ling; Wu, Hua-Wang; Cai, Pei-Qiang; Qiu, Ying-Wei; Zhang, Xue-Lin; Jiang, Gui-Hua

    2015-01-01

    Previous studies have shown that patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt hepatic encephalopathy (OHE) are associated with a varying degree of cognitive dysfunction. Several resting-state functional magnetic resonance imaging (fMRI) studies have been conducted to explore the neural correlates of such cognitive deficits, whereas little effort has been made to investigate the cortical integrity in cirrhotic patients without OHE. Here, using cortical thickness, surface area and local gyrification index (lGI), this study performed a comprehensive analysis on the cortical morphometry of patients with HBV-RC without OHE (HBV-RC-NOHE) vs. matched healthy controls. Compared with healthy controls, we found significantly increased cortical thickness in the bilateral lingual and parahippocampal gyrus, right posterior cingulate cortex, precuneus, peri-calcarine sulcus and fusiform gyrus in patient with HBV-RC-NOHE, which may closely relate to be the low-grade brain edema. Cortical gyrification analysis showed significantly increased lGI in the left superior and inferior parietal cortex as well as lateral occipital cortex, which was speculated to be associated with disruptions in white matter connectivity and sub-optimal intra-cortical organization. In addition, the mean cortical thickness/lGI of the regions with structural abnormalities was shown to be negatively correlated with psychometric hepatic encephalopathy score (PHES) of the patients with HBV-RC-NOHE. These morphological changes may serve as potential markers for the preclinical diagnosis and progression of HBV-RC-NOHE. PMID:26106307

  19. Inflammation Promotes Expression of Stemness-Related Properties in HBV-Related Hepatocellular Carcinoma.

    PubMed

    Chang, Te-Sheng; Chen, Chi-Long; Wu, Yu-Chih; Liu, Jun-Jen; Kuo, Yung Che; Lee, Kam-Fai; Lin, Sin-Yi; Lin, Sey-En; Tung, Shui-Yi; Kuo, Liang-Mou; Tsai, Ying-Huang; Huang, Yen-Hua

    2016-01-01

    The expression of cancer stemness is believed to reduce the efficacy of current therapies against hepatocellular carcinoma (HCC). Understanding of the stemness-regulating signaling pathways incurred by a specific etiology can facilitate the development of novel targets for individualized therapy against HCC. Niche environments, such as virus-induced inflammation, may play a crucial role. However, the mechanisms linking inflammation and stemness expression in HCC remain unclear. Here we demonstrated the distinct role of inflammatory mediators in expressions of stemness-related properties involving the pluripotent octamer-binding transcription factor 4 (OCT4) in cell migration and drug resistance of hepatitis B virus-related HCC (HBV-HCC). We observed positive immunorecognition for macrophage chemoattractant protein 1 (MCP-1)/CD68 and OCT4/NANOG in HBV-HCC tissues. The inflammation-conditioned medium (inflamed-CM) generated by lipopolysaccharide-stimulated U937 human leukemia cells significantly increased the mRNA and protein levels of OCT4/NANOG preferentially in HBV-active (HBV+HBsAg+) HCC cells. The inflamed-CM also increased the side population (SP) cell percentage, green fluorescent protein (GFP)-positive cell population, and luciferase activity of OCT4 promoter-GFP/luciferase in HBV-active HCC cells. Furthermore, the inflamed-CM upregulated the expressions of insulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) and activated IGF-IR/Akt signaling in HBV-HCC. The IGF-IR phosphorylation inhibitor picropodophyllin (PPP) suppressed inflamed-CM-induced OCT4 and NANOG levels in HBV+HBsAg+ Hep3B cells. Forced expression of OCT4 significantly increased the secondary sphere formation and cell migration, and reduced susceptibility of HBV-HCC cells to cisplatin, bleomycin, and doxorubicin. Taking together, our results show that niche inflammatory mediators play critical roles in inducing the expression of stemness-related properties involving IGF-IR activation, and

  20. Inflammation Promotes Expression of Stemness-Related Properties in HBV-Related Hepatocellular Carcinoma

    PubMed Central

    Wu, Yu-Chih; Liu, Jun-Jen; Kuo, Yung Che; Lee, Kam-Fai; Lin, Sin-Yi; Lin, Sey-En; Tung, Shui-Yi; Kuo, Liang-Mou; Tsai, Ying-Huang; Huang, Yen-Hua

    2016-01-01

    The expression of cancer stemness is believed to reduce the efficacy of current therapies against hepatocellular carcinoma (HCC). Understanding of the stemness-regulating signaling pathways incurred by a specific etiology can facilitate the development of novel targets for individualized therapy against HCC. Niche environments, such as virus-induced inflammation, may play a crucial role. However, the mechanisms linking inflammation and stemness expression in HCC remain unclear. Here we demonstrated the distinct role of inflammatory mediators in expressions of stemness-related properties involving the pluripotent octamer-binding transcription factor 4 (OCT4) in cell migration and drug resistance of hepatitis B virus-related HCC (HBV-HCC). We observed positive immunorecognition for macrophage chemoattractant protein 1 (MCP-1)/CD68 and OCT4/NANOG in HBV-HCC tissues. The inflammation-conditioned medium (inflamed-CM) generated by lipopolysaccharide-stimulated U937 human leukemia cells significantly increased the mRNA and protein levels of OCT4/NANOG preferentially in HBV-active (HBV+HBsAg+) HCC cells. The inflamed-CM also increased the side population (SP) cell percentage, green fluorescent protein (GFP)-positive cell population, and luciferase activity of OCT4 promoter-GFP/luciferase in HBV-active HCC cells. Furthermore, the inflamed-CM upregulated the expressions of insulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) and activated IGF-IR/Akt signaling in HBV-HCC. The IGF-IR phosphorylation inhibitor picropodophyllin (PPP) suppressed inflamed-CM-induced OCT4 and NANOG levels in HBV+HBsAg+ Hep3B cells. Forced expression of OCT4 significantly increased the secondary sphere formation and cell migration, and reduced susceptibility of HBV-HCC cells to cisplatin, bleomycin, and doxorubicin. Taking together, our results show that niche inflammatory mediators play critical roles in inducing the expression of stemness-related properties involving IGF-IR activation, and

  1. [Advanced Testing and Laboratory for HBV, HCV, and HIV Infection].

    PubMed

    Deguchi, Matsuo

    2015-06-01

    Most target substances for immunoassay of infectious disease are antigens or antibodies which do not exist in the human body. Therefore, the method to set reference values is different from chemistry or hematology testing. High sensitivity is required for infectious disease testing, particularly for screening. Also, its reference values (cut-off values) are set as low as possible. Therefore, a false-positive reaction can be caused due to slightly non-specific reactions in infectious disease reagents. The specificities for infectious disease reagents were evaluated with 9 kinds of HCV antibody test kit and 9 kinds of HIV screening kit. The frequencies of false-positive results were 0.2-1.8 and 0.2-1.3%, respectively, and even a kit with a high specificity showed a false-positive result for 1 in 500 samples. The sensitivities for infectious disease reagents were evaluated with a newly developed super-high- sensitive HBs antigen assay kit and 8 kinds of chemiluminescence HBs antigen assay kit which are highly sensitive conventional kits. As a result, the super-high-sensitive kit was 10 to 40 times more sensitive than conventional kits. After introducing the super-high-sensitive kit to routine assays, 16 HBV-infected patients, who were not identified with the conventional kits, were detected for six months. On the other hand, we confirmed false-positive results due to contamination between specimens after introducing the super-high-sensitive kit. It is recommended to use the super-high-sensitive kit in a well-controlled environment to prevent contamination between specimens in order to generate highly reliable test results. PMID:26548240

  2. PRO-140 (Progenics).

    PubMed

    Poli, G

    2001-09-01

    PRO-140, a monoclonal antibody against the HIV coreceptor CCR5, is under investigation by Progenics and the Aaron Diamond AIDS Research Center (ADARC) as a potential treatment for HIV infection [211441], [286246], [286247]. Phase I/II trials were expected to commence during 2001 [395621], [409142], despite being initially planned for 2000 [322637], [361819], [365216], [375598], [408483]. In January 1998, ADARC and Progenics reported that the HIV binding site on the CCR5 coreceptor is distinct from betachemokine binding domains, which they claimed may allow for the development of therapeutics with fewer side effects [273391], 421256]. In vitro studies have shown PRO-140 potently blocked all of 17 primary HIV isolates that use CCR5 as a fusion coreceptor [342173]. In October 2000, Progenics was awarded an SBIR grant to fund a 2-year project exploring the breadth, potency and durability of PRO-140 therapy in laboratory and animal models of HIV infection. This project was a collaboration between Progenics, Weill Medical College of Cornell University and the Scripps Research Institute [385982]. In May 1999, the company entered into an agreement with Protein Design Labs (PDL) for the humanization by PDL of PRO-140 [325445]. In November 1997, Progenics was awarded a 600,000 dollars grant from the NIAID for the examination of new approaches to HIV vaccine design based on CCR5 [268407]. PMID:15965853

  3. TOXIRAE PRO PID

    EPA Science Inventory

    The ToxiRAE Pro PID measures total volatile organic compounds (VOCs) using a photoionization detector (PID). This sensor can be programmed to measure concentrations of a specified compound automatically and has a real time reading of VOC concentrations in parts per million (ppm) ...

  4. Hepatitis B virus infection in blood donors in Argentina: prevalence of infection, genotype distribution and frequency of occult HBV infection.

    PubMed

    Pisano, María Belén; Blanco, Sebastián; Carrizo, Horacio; Ré, Viviana Elizabeth; Gallego, Sandra

    2016-10-01

    This study describes the prevalence of HBV infection based on detection of HBsAg and HBV-DNA by NAT in 70,102 blood donors in Argentina (Córdoba province) and shows the viral genotype distribution and frequency of occult HBV infection (OBI) in this population. Forty-two donors were confirmed positive for HBV infection (0.06 %), and four had OBI. Genotype F was the most prevalent (71.4 %), followed by A (14.3 %), C (7.1 %) and D (7.1 %). This is the first report of the prevalence of confirmed HBV infection and the high frequency of occult HBV infection in a blood bank in Argentina. PMID:27383207

  5. Complete Spectrum of CRISPR/Cas9-induced Mutations on HBV cccDNA.

    PubMed

    Seeger, Christoph; Sohn, Ji A

    2016-08-01

    Hepatitis B virus (HBV) causes chronic infections that cannot yet be cured. The virus persists in infected hepatocytes, because covalently closed circular DNA (cccDNA), the template for the transcription of viral RNAs, is stable in nondividing cells. Antiviral therapies with nucleoside analogues inhibit HBV DNA synthesis in capsids in the cytoplasm of infected hepatocytes, but do not destroy nuclear cccDNA. Because over 200 million people are still infected, a cure for chronic hepatitis B (CHB) has become one of the major challenges in antiviral therapy. As a first step toward the development of curative therapies, we previously demonstrated that the CRISPR/Cas9 system can be used to functionally inactivate cccDNA derived from infectious HBV. Moreover, some evidence suggests that certain cytokines might induce an APOBEC-mediated cascade leading to the destruction of cccDNA. In this report we investigated whether a combination of the two mechanisms could act synergistically to inactivate cccDNA. Using next generation sequencing (NGS), we determined the complete spectrum of mutations in cccDNA following Cas9 cleavage and repair by nonhomologous end joining (NHEJ). We found that over 90% of HBV DNA was cleaved by Cas9. In addition our results showed that editing of HBV DNA after Cas9 cleavage is at least 15,000 times more efficient that APOBEC-mediated cytosine deamination following treatment of infected cells with interferon alpha (IFNα). We also found that a previously used method to detect cytosine deaminated DNA, termed 3D-PCR, overestimates the amount and frequency of edited HBV DNA. Taken together, our results demonstrated that the CRISPR/Cas9 system is so far the best method to functionally inactivate HBV cccDNA and provide a cure for CHB. PMID:27203444

  6. Liver type I regulatory T cells suppress germinal center formation in HBV-tolerant mice.

    PubMed

    Xu, Long; Yin, Wenwei; Sun, Rui; Wei, Haiming; Tian, Zhigang

    2013-10-15

    The liver plays a critical role in inducing systemic immune tolerance, for example, during limiting hypersensitivity to food allergy and in rendering acceptance of allotransplant or even hepatotropic pathogens. We investigated the unknown mechanisms of liver tolerance by using an established hepatitis B virus (HBV)-carrier mouse model, and found that these mice exhibited an antigen-specific tolerance toward peripheral HBsAg vaccination, showing unenlarged draining lymph node (DLN), lower number of germinal centers (GC), and inactivation of GC B cells and follicular T helper (Tfh) cells. Both in vivo and in vitro immune responses toward HBsAg were suppressed by mononuclear cells from HBV-carrier mice, which were CD4(+) Foxp3(-) type 1 regulatory T (Tr1)-like cells producing IL-10. Using recipient Rag1(-/-) mice, hepatic Tr1-like cells from day 7 of HBV-persistent mice acquired the ability to inhibit anti-HBV immunity 3 d earlier than splenic Tr1-like cells, implying that hepatic Tr1-like cells were generated before those in spleen. Kupffer cell depletion or IL-10 deficiency led to impairment of Tr1-like cell generation, along with breaking HBV persistence. The purified EGFP(+)CD4(+) T cells (containing Tr1-like cells) from HBV-carrier mice trafficked in higher numbers to DLN in recipient mice after HBsAg vaccination, and subsequently inactivated both Tfh cells and GC B cells via secreting IL-10, resulting in impaired GC formation and anti-HB antibody production. Thus, our results indicate Tr1-like cells migrate from the liver to the DLN and inhibit peripheral anti-HBV immunity by negatively regulating GC B cells and Tfh cells. PMID:24089450

  7. Performance evaluation of ExiStation HBV diagnostic system for hepatitis B virus DNA quantitation.

    PubMed

    Cha, Young Joo; Yoo, Soo Jin; Sohn, Yong-Hak; Kim, Hyun Soo

    2013-11-01

    The performance of a recently developed real-time PCR system, the ExiStation HBV diagnostic system, for quantitation of hepatitis B virus (HBV) in human blood was evaluated. The detection limit, reproducibility, cross-reactivity, and interference were evaluated as measures of analytical performance. For the comparison study, 100 HBV-positive blood samples and 100 HBV-negative samples from Korean Blood Bank Serum were used, and the results of the ExiStation HBV system showed good correlation with those obtained using the Cobas TaqMan (r2=0.9931) and Abbott real-time PCR systems (r2=0.9894). The lower limit of detection was measured as 9.55 IU/mL using WHO standards and the dynamic range was linear from 6.68 to 6.68×10(9) IU/mL using cloned plasmids. The within-run coefficient of variation (CV) was 9.4%, 2.1%, and 1.1%, and the total CV was 11.8%, 3.6%, and 1.7% at a concentration of 1.92 log10 IU/mL, 3.88 log10 IU/mL, and 6.84 log10 IU/mL, respectively. No cross-reactivity or interference was detected. The ExiStation HBV diagnostic system showed satisfactory analytical sensitivity, excellent reproducibility, no cross-reactivity, no interference, and high agreement with the Cobas TaqMan and Abbott real-time PCR systems, and is therefore a useful tool for the detection and monitoring of HBV infection. PMID:23892129

  8. Hepatitis B vaccination with or without hepatitis B immunoglobulin at birth to babies born of HBsAg-positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babies: a randomized controlled trial.

    PubMed

    Pande, C; Sarin, S K; Patra, S; Kumar, A; Mishra, S; Srivastava, S; Bhutia, K; Gupta, E; Mukhopadhyay, C K; Dutta, A K; Trivedi, S S

    2013-11-01

    Vertical transmission of Hepatitis B virus HBV can result in a state of chronic HBV infection and its complications. HBV vaccination with or without hepatitis B immunoglobulin (HBIG) prevents transmission of overt infection to the babies. However, whether it also prevents occult HBV infection in babies is not known. Consecutive pregnant women of any gestation found to be HBsAg positive were followed till delivery, and their babies were included in the study. Immediately after delivery, babies were randomized to receive either HBIG or placebo in addition to recombinant HBV vaccine (at 0, 6, 10 and 14 weeks). The primary end-point of the study, assessed at 18 weeks of age, was remaining free of any HBV infection (either overt or occult) plus the development of adequate immune response to vaccine. The babies were further followed up for a median of 2 years of age to determine their eventual outcome. Risk factors for HBV transmission and for poor immune response in babies were studied. Of the 283 eligible babies, 259 were included in the trial and randomized to receive either HBIG (n=128) or placebo (n=131) in addition to recombinant HBV vaccine. Of the 222 of 259 (86%) babies who completed 18 weeks of follow-up, only 62/222 (28%) reached primary end-point. Of the remaining, 6/222 (3%) developed overt HBV infection, 142/222 (64%) developed occult HBV infection, and 12/222 (5%) had no HBV infection but had poor immune response. All 6 overt infections occurred in the placebo group (P=0.030), while occult HBV infections were more common in the HBIG group (76/106 [72%] vs. 66/116 [57%]; P=0.025). This may be due to the immune pressure of HBIG. There was no significant difference between the two groups in frequency of babies developing poor immune response or those achieving primary end-point. The final outcome of these babies at 24 months of age was as follows: overt HBV infection 4%, occult HBV infection 42%, no HBV infection but poor immune response 8% and no HBV

  9. Changes in Innate and Permissive Immune Responses after HBV Transgenic Mouse Vaccination and lLong-Term-siRNA Treatment

    PubMed Central

    Fang, Ying; Ma, Heng-Hao; Xu, Man-Chun; Zhang, Hong-Bin; Zhang, Wei-Yun; Zhao, Ya-Gang; Sun, Da-Yong; Hu, Wen-Kui; Liu, Jian

    2013-01-01

    Background Currently, no licensed therapy can thoroughly eradicate hepatitis B virus (HBV) from the body, including interferon α and inhibitors of HBV reverse-transcription. Small interfering RNA (siRNA) seem to be a promising tool for treating HBV, but had no effect on the pre-existing HBV covalently closed circular DNA. Because it is very difficult to thoroughly eradicate HBV with unique siRNAs, upgrading the immune response is the best method for fighting HBV infection. Here, we aim to explore the immune response of transgenic mice to HBV vaccination after long-term treatment with siRNAs and develop a therapeutic approach that combines siRNAs with immunopotentiators. Methodology/Principal Findings To explore the response of transgenic mice to hepatitis B vaccine, innate and acquired immunity were detected after long-term treatment with siRNAs and vaccination. Antiviral cytokines and level of anti-hepatitis B surface antigen antibody (HBsAg-Ab) were measured after three injections of hepatitis B vaccine. Results Functional analyses indicated that toll-like receptor-mediated innate immune responses were reinforced, and antiviral cytokines were significantly increased, especially in the pSilencer4.1/HBV groups. Analysis of CD80+/CD86+ dendritic cells in the mouse liver indicated that dendritic cell antigen presentation was strengthened. Furthermore, the siRNA-treated transgenic mice could produce detectable HBsAg-Ab after vaccination, especially in the CpG oligonucleotide vaccine group. Conclusions/Significance For the first time, our studies demonstrate that siRNAs with CpG HBV vaccine could strengthen the immune response and break the immune tolerance status of transgenic mice to HBV. Thus, siRNAs and HBV vaccine could provide a sharp double-edged sword against chronic HBV infection. PMID:23472088

  10. Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation

    PubMed Central

    Tropberger, Philipp; Mercier, Alexandre; Robinson, Margaret; Zhong, Weidong; Ganem, Don E.; Holdorf, Meghan

    2015-01-01

    Chronic hepatitis B virus (HBV) infection affects 240 million people worldwide and is a major risk factor for liver failure and hepatocellular carcinoma. Current antiviral therapy inhibits cytoplasmic HBV genomic replication, but is not curative because it does not directly affect nuclear HBV closed circular DNA (cccDNA), the genomic form that templates viral transcription and sustains viral persistence. Novel approaches that directly target cccDNA regulation would therefore be highly desirable. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications (PTMs). Here, using a new cccDNA ChIP-Seq approach, we report, to our knowledge, the first genome-wide maps of PTMs in cccDNA-containing chromatin from de novo infected HepG2 cells, primary human hepatocytes, and from HBV-infected liver tissue. We find high levels of PTMs associated with active transcription enriched at specific sites within the HBV genome and, surprisingly, very low levels of PTMs linked to transcriptional repression even at silent HBV promoters. We show that transcription and active PTMs in HBV chromatin are reduced by the activation of an innate immunity pathway, and that this effect can be recapitulated with a small molecule epigenetic modifying agent, opening the possibility that chromatin-based regulation of cccDNA transcription could be a new therapeutic approach to chronic HBV infection. PMID:26438841

  11. [Assessment of mother-to-child HBV transmission at the prenatal consultation in Vientiane, Laos].

    PubMed

    Xaydalasouk, K; Keomalaphet, S; Latthaphasavang, V; Souvong, V; Buisson, Y

    2016-02-01

    Chronic infection with hepatitis B virus (HBV) remains highly endemic in Laos, mainly related to mother to child transmission. Despite the introduction of the vaccination against HBV in the Expanded Programme on Immunization in 2001 and the administration of a vaccine birth dose as part of a 3-dose schedule since 2004, infant immunization coverage remains inadequate because most mothers are not aware of the risks. A survey was conducted in early 2013 in Vientiane capital among women who undergo serologic screening for hepatitis B at the prenatal consultation, to assess their knowledge and risk factors of HBV infection. It included the administration of a standardized questionnaire divided into four parts (socio-demographic data, knowledge about hepatitis B, risk factors and immunization status) and a screening test for the HBV surface antigen (HBsAg). A total of 200 pregnant women were recruited consecutively in Mahosot hospital. They were aged 14-39 years (mean 27 ± 4.76 years), civil servants (37%) or housewives (33.5%) with a secondary or higher education level (80%). Most were multiparous (68.5%) and attended antenatal care in the third trimester of pregnancy (61%). Sixteen (8%) tested HBsAg positive. The HBsAg seroprevalence was higher in the 26-30 years age group, among women above the primary school education level and women practicing the profession of shopkeeper or civil servant, but these differences were not significant. Hepatitis B was known by a small majority (53%) but 26% could name the routes of transmission, 28% considered it as a serious illness and 24.5% were aware of the HBV vaccine. No risk factor for blood or sexual exposure to HBVinfection was significantly linked to the HBsAg carriage. In this sample of pregnant women mostly urban, educated and multiparous with access to a central hospital, the high rate of HBV infection and the low level of knowledge about the risk of mother-to-child HBV transmission reveals a major gap in information and

  12. Anti-HBV activity and mechanism of marine-derived polyguluronate sulfate (PGS) in vitro.

    PubMed

    Wu, Lijuan; Wang, Wei; Zhang, Xiaoshuang; Zhao, Xia; Yu, Guangli

    2016-06-01

    Polyguluronate sulfate (PGS) is a low molecular-weight sulfated derivative, which has a structure of 2,3-O-disulfated-1,4-poly-l-guluronic acid (PG) with about 1.5 sulfate per sugar residue. Herein, our results showed that PGS effectively inhibited the expression and secretion of HBsAg and HBeAg in HepG2.2.15 cells. PGS could bind and enter into HepG2.2.15 cells to interfere with HBV transcription rather than blocking HBV DNA replication. Moreover, PGS also enhanced the production and secretion of interferon beta (IFN-β) in HepG2.2.15 cells. Cellular NF-κB and Raf/MEK/ERK signaling pathways were also involved in the anti-HBV actions of PGS. Thus, PGS may inhibit HBV replication through upregulating the NF-κB and Raf/MEK/ERK pathways to enhance the interferon system. In summary, PGS merits further investigation as a novel anti-HBV agent aimed at modulating the host innate immune system in the future. PMID:27083353

  13. Humanized Murine Model for HBV and HCV Using Human Induced Pluripotent Stem Cells

    PubMed Central

    Zhou, Xiao-Ling; Sullivan, Gareth J.; Sun, Pingnan; Park, In-Hyun

    2013-01-01

    Infection of hepatitis B virus (HBV) and hepatitis C virus (HCV) results in heterogeneous outcomes from acute asymptomatic infection to chronic infection leading to cirrhosis and hepatocellular carcinoma (HCC). In vitro models using animal hepatocytes, human HCC cell lines, or in vivo transgenic mouse models have contributed invaluably to understanding the pathogenesis of HBV and HCV. A humanized mouse model made by reconstitution of human primary hepatocytes in the liver of the immunodeficient mouse provides a novel experimental opportunity which mimics the in vivo growth of the human hepatocytes. The limited access to primary human hepatocytes necessitated the search for other cellular sources, such as pluripotent stem cells. Human embryonic stem cells (hESCs) have the features of self-renewal and pluripotency and differentiate into cells of all three germ layers, including hepatocytes. Humaninduced pluripotent stem cells (iPSCs) derived from the patient’s or individual’s own cells provide a novel opportunity to generate hepatocyte-like cells with the defined genetic composition. Here, we will review the current perspective of the models used for HBV and HCV study, and introduce the personalized mouse model using human iPSCs. This novel mouse model will facilitate the direct investigation of HBV and HCV in human hepatocytes as well as probing the genetic influence on the susceptibility of hepatocytes to HBV and HCV. PMID:22370780

  14. Resveratrol enhances HBV replication through activating Sirt1-PGC-1α-PPARα pathway

    PubMed Central

    Shi, Yixian; Li, Yongjun; Huang, Chenjie; Ying, Lixiong; Xue, Jihua; Wu, Haicong; Chen, Zhi; Yang, Zhenggang

    2016-01-01

    The population of hepatitis B combined with a number of metabolic disorders is increasing significantly. Resveratrol (RSV) has been used as a preclinical drug for the treatment of the metabolic disorders. However, the impact of RSV on HBV replication remains unknown. In this study, the HBV-expressing hepatocelluar carcinoma cell line and mouse model created by hydrodynamic injection of viral DNA were used. We found that RSV activates Sirt1, which in turn deacetylates PGC-1α and subsequently increases the transcriptional activity of PPARα, leading to the enhanced HBV transcription and replication in vitro and in vivo. In addition, we found that this pathway is also required for fasting-induced HBV transcription. Taken together, this study identifies that RSV enhances HBV transcription and replication especially acting on the core promoter, which depends on Sirt1-PGC-1α-PPARα pathway. We conclude that RSV may exacerbate the progression of hepatitis B and that patients with hepatitis B infection should be cautious taking RSV as a dietary supplement. PMID:27098390

  15. Resveratrol enhances HBV replication through activating Sirt1-PGC-1α-PPARα pathway.

    PubMed

    Shi, Yixian; Li, Yongjun; Huang, Chenjie; Ying, Lixiong; Xue, Jihua; Wu, Haicong; Chen, Zhi; Yang, Zhenggang

    2016-01-01

    The population of hepatitis B combined with a number of metabolic disorders is increasing significantly. Resveratrol (RSV) has been used as a preclinical drug for the treatment of the metabolic disorders. However, the impact of RSV on HBV replication remains unknown. In this study, the HBV-expressing hepatocelluar carcinoma cell line and mouse model created by hydrodynamic injection of viral DNA were used. We found that RSV activates Sirt1, which in turn deacetylates PGC-1α and subsequently increases the transcriptional activity of PPARα, leading to the enhanced HBV transcription and replication in vitro and in vivo. In addition, we found that this pathway is also required for fasting-induced HBV transcription. Taken together, this study identifies that RSV enhances HBV transcription and replication especially acting on the core promoter, which depends on Sirt1-PGC-1α-PPARα pathway. We conclude that RSV may exacerbate the progression of hepatitis B and that patients with hepatitis B infection should be cautious taking RSV as a dietary supplement. PMID:27098390

  16. Presence of anti-HBc is associated to high rates of HBV resolved infection and low threshold for Occult HBV Infection in HIV patients with negative HBsAg in Chile.

    PubMed

    Vargas, Jose Ignacio; Jensen, Daniela; Sarmiento, Valeska; Peirano, Felipe; Acuña, Pedro; Fuster, Felipe; Soto, Sabrina; Ahumada, Rodrigo; Huilcaman, Marco; Bruna, Mario; Jensen, Werner; Fuster, Francisco

    2016-04-01

    HBV-HIV coinfection is prevalent. Frequently, anti-HBc is the only serological marker of HBV, which can be indicative of HBV resolved infection, when found together with anti-HBs reactivity; or present as "isolated anti-HBc," related to HBV occult infection with presence of detectable DNA HBV, more prevalent in HIV-positive individuals. Regional data about this condition are scarce. Anti-HBc rapid test has been used as screening, but its performance has not been described in HIV-positive patients. The aim of this study was determine prevalence of anti-HBc in HIV-positive patients, serological pattern of HBV resolved infection and isolated anti-HBc, evaluating presence of HBV occult infection. Assess anti-HBc rapid test compared to ECLIA. Methods included measurement of anti-HBc and anti-HBs in HIV-positive patients with negative HBsAg. Serum HBV DNA quantification and HBV booster vaccination to "isolated anti-HBc" individuals. Detection of anti-HBc by rapid test and ECLIA. In 192 patients, prevalence of anti-HBc was 42.7% (82/192); associated to male gender, drug use, men-sex-men, positive-VDRL, and longer time HIV diagnosis. 34.4% (66/192) had presence of anti-HBs, mean titers of 637 ui/ml. Isolated anti-HBc in 8.3% (16/192), associated to detectable HIV viral load and no-use of HAART; in them, HBV DNA was undetectable, and 60% responded to HBV vaccination booster. Anti-HBc rapid test showed low sensibility (32.9%) compared to ECLIA. These results show that prevalence of anti-HBc in HIV-positive individuals is high, in most cases accompanied with anti-HBs as HBV resolved infection. Low prevalence of "isolated anti-HBc," with undetectable HBV DNA, and most had anamnestic response to HBV vaccination; suggest low possibility of occult HBV infection. Anti-HBc rapid test cannot be recommended as screening method for anti-HBc. PMID:26381185

  17. Inhibition of the HCV core protein on the immune response to HBV surface antigen and on HBV gene expression and replication in vivo.

    PubMed

    Zhu, Wenbo; Wu, Chunchen; Deng, Wanyu; Pei, Rongjun; Wang, Yun; Cao, Liang; Qin, Bo; Lu, Mengji; Chen, Xinwen

    2012-01-01

    The hepatitis C virus (HCV) core protein is a multifunctional protein that can interfere with the induction of an immune response. It has been reported that the HCV core protein inhibits HBV replication in vitro. In this study, we test the effect of the HCV core gene on the priming of the immune response to hepatitis B surface antigen (HBsAg) and on the replication of HBV in vivo. Our results showed that the full-length HCV core gene inhibits the induction of an immune response to the heterogeneous antigen, HBsAg, at the site of inoculation when HCV core (pC191) and HBsAg (pHBsAg) expression plasmids are co-administered as DNA vaccines into BALB/c mice. The observed interference effect of the HCV core occurs in the priming stage and is limited to the DNA form of the HBsAg antigen, but not to the protein form. The HCV core reduces the protective effect of the HBsAg when the HBsAg and the HCV core are co-administered as vaccines in an HBV hydrodynamic mouse model because the HCV core induces immune tolerance to the heterogeneous HBsAg DNA antigen. These results suggest that HCV core may play an important role in viral persistence by the attenuation of host immune responses to different antigens. We further tested whether the HCV core interfered with the priming of the immune response in hepatocytes via the hydrodynamic co-injection of an HBV replication-competent plasmid and an HCV core plasmid. The HCV core inhibited HBV replication and antigen expression in both BALB/c (H-2d) and C57BL/6 (H-2b) mice, the mouse models of acute and chronic hepatitis B virus infections. Thus, the HCV core inhibits the induction of a specific immune response to an HBsAg DNA vaccine. However, HCV C also interferes with HBV gene expression and replication in vivo, as observed in patients with coinfection. PMID:23024803

  18. Evolutionary analysis of HBV "S" antigen genetic diversity in Iranian blood donors: a nationwide study.

    PubMed

    Pourkarim, Mahmoud Reza; Sharifi, Zohre; Soleimani, Ali; Amini-Bavil-Olyaee, Samad; Elsadek Fakhr, Ahmed; Sijmons, Steven; Vercauteren, Jurgen; Karimi, Gharib; Lemey, Philippe; Maes, Piet; Alavian, Seyed Moayed; Van Ranst, Marc

    2014-01-01

    The genetic diversity of the HBV S gene has a significant impact on the prophylaxis and treatment of hepatitis B infection. The effect of selective pressure on this genetic alteration has not yet been studied in Iranian blood donors. To explore HBV evolution and to analyze the effects and patterns of hepatitis B surface antigen (HBsAg) mutations on blood screening assays, 358 Iranian blood donors diagnosed as asymptomatic HBV carriers were enrolled in this nationwide study. Large S and partial S genes were amplified and sequenced. HBV (sub) genotypes and synonymous and nonsynonymous mutations were investigated. The impact of naturally occurring mutations on HBsAg ELISA results was explored. Phylogenetic analyses revealed that isolated strains were of genotype D. The dominant subgenotype/subtype was D1/ayw2. Deletions and naturally occurring stop codons in the pre-S1 and major hydrophilic region (MHR) were identified. In total, 32.8% of the studied strains harbored 195 single or multiple mutations in the MHR, the majority of which were located at the first loop of the "a determinant" domain. The ayw2 subtype showed a significant effect on the ELISA signal/cut-off value and carried fewer mutations in the MHR. Nonsynonymous/synonymous substitution value indicated that negative selection was the dominant evolutionary force in the HBV S gene. This nationwide study revealed that mutation frequency of HBsAg among Iranian blood donors was much higher than previous reports from the different local regions. These findings regarding the significant differences in reactivity of ELISA among different subtypes of HBV and its correlation with the number of mutations at the MHR will be valuable to public health authorities. PMID:24150816

  19. HIV, HBV, and HCV molecular epidemiology among trans (transvestites, transsexuals, and transgender) sex workers in Argentina.

    PubMed

    Carobene, Mauricio; Bolcic, Federico; Farías, María Sol Dos Ramos; Quarleri, Jorge; Avila, María Mercedes

    2014-01-01

    Commercial sex work is frequent among male-to-female transvestites, transsexuals and transgenders in Argentina, leading to high susceptibility to HIV, HBV, and HCV among other sexually transmitted infections. In a global context of scarce data on the trans sex workers population, this study was aimed to study the genomic characterization of these viruses. Plasma presence of HIV, HBV, and HCV genomic material was evaluated in samples from 273 trans sex workers. Genomic sequences of HIV-gag, pol, and vif-vpu genes, HBV-S gene, and HCV-5'UT and NS5B genes were obtained. Molecular characterization involved phylogenetic analysis and several in silico tools. Resistance-associated mutations in HIV and HBV pol genes were also analyzed. The HIV genomic characterization in 62 trans sex workers samples showed that 54.8% of the isolates corresponded to BF intersubtype recombinants, and 38.7% to subtype B. The remaining were classified as subtypes C (4.8%) and A (1.6%). HBV and HCV co-infection prevalence among HIV positive trans sex workers yielded rates of 3.2% and 6.5% respectively. Drug resistance-associated mutations were found in 12/62 (19%) HIV pol sequences, but none among HBV. Based on phylogenetic relationships, HIV isolates characterized as subtypes BF and B appeared intermingled with those from other high-risk groups. Despite trans sex workers declared not to have received antiviral treatment, complex drug resistance-associated mutation patterns were found in several HIV isolates. Planned prevention, screening, and treatment are needed to reduce further transmission and morbidity. PMID:24123155

  20. Functional analysis of 'a' determinant mutations associated with occult HBV in HIV-positive South Africans.

    PubMed

    Powell, Eleanor A; Boyce, Ceejay L; Gededzha, Maemu P; Selabe, Selokela G; Mphahlele, M Jeffrey; Blackard, Jason T

    2016-07-01

    Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in the absence of hepatitis B surface antigen (HBsAg). Occult HBV is associated with the development of hepatocellular carcinoma, reactivation during immune suppression, and virus transmission. Viral mutations contribute significantly to the occult HBV phenotype. Mutations in the 'a' determinant of HBsAg are of particular interest, as these mutations are associated with immune escape, vaccine escape and diagnostic failure. We examined the effects of selected occult HBV-associated mutations identified in a population of HIV-positive South Africans on HBsAg production in vitro. Mutations were inserted into two different chronic HBV backbones and transfected into a hepatocyte-derived cell line. HBsAg levels were quantified by enzyme-linked immunosorbent assay (ELISA), while the detectability of mutant HBsAg was determined using an HA-tagged HBsAg expression system. Of the seven mutations analysed, four (S132P, C138Y, N146D and C147Y) resulted in decreased HBsAg expression in one viral background but not in the second viral background. One mutation (N146D) led to a decrease in HBsAg detected as compared to HA-tag, indicating that this mutation compromises the ability of the ELISA to detect HBsAg. The contribution of occult-associated mutations to the HBsAg-negative phenotype of occult HBV cannot be determined adequately by testing the effect of the mutation in a single viral background, and rigorous analysis of these mutations is required. PMID:27031988

  1. Isolation of the neutralization ScFvs Against HBV infection from the Immunized Population.

    PubMed

    Bai, Yin; Chen, Yanmin; Zhang, Nan; Guo, Xiaochen; Zhao, Jingzhuang; Wang, Fuxiang; Xu, Pengfei; Yuan, Qingyan; Qi, Jianying; Wang, Wenfei; Li, Deshan; Ren, Guiping

    2015-01-01

    For a long time, researchers have attempted to replace human plasmaderived immunoglobulin against HBV with recombinant HBV antibodies for therapeutic purposes, but failed to develop the products. One of the reasons may be lack of high throughput antibody screening tool. In this study, we screened an antibody library from immunized subjects by a powerful bacterial display technology. The capacity of the ScFv library was 10(9), 117 individual clones against HBV pre- S1 were initially selected and sequenced, the homology of these clones ranged from 59.7% -68.7%. Ten clones were randomly selected based on florescence intensity by FACS. The ScFv antibodies were expressed in E.coli and purified to examine their neutralization ability. First, we tested the ability of these clones to block the binding of the pre-S1 polypeptide to the HBV sensitive cells Chang liver cells and HepG2 cells, then, we examined the ability of these clones to inhibit the infection of the Change liver cells by HBV released from HepG2.2.15 cells by detection of viral DNA and hepatitis B virus e antigen (HBeAg) in the supernatant of Chang liver cells. Results showed that 4 (clone 3, 7, 9 and 31) out of the ten clones could significantly reduce the binding of pre-S1 polypeptide to Chang liver cells in a dose-dependent manner. Treatment with the same clones (clone 3, 7, 9 and 31) could dramatically reduce the contents of HBV DNA in the media of the infected Chang liver cells by 29.4, 7.89, 58.8, 76.9, respectively, and the amount of HBeAg by 60.2%, 32.6%, 66.1% and 68.1%, respectively. These results suggest that these clones can neutralize HBV infection and have the potential to become therapeutic antibodies against HBV infection to replace the human plasma-derived immunoglobulin. PMID:26144596

  2. Hepatitis B virus (HBV)-specific cytotoxic T-cell (CTL) response in humans: characterization of HLA class II-restricted CTLs that recognize endogenously synthesized HBV envelope antigens.

    PubMed Central

    Penna, A; Fowler, P; Bertoletti, A; Guilhot, S; Moss, B; Margolskee, R F; Cavalli, A; Valli, A; Fiaccadori, F; Chisari, F V

    1992-01-01

    In this study, we show that CD4+, hepatitis B virus (HBV) envelope-specific T-cell clones produced by stimulation with a particulate antigen preparation are able to recognize and kill not only autologous antigen-presenting cells incubated with exogenous HBV envelope antigens but also autologous HLA class II-positive cells expressing endogenously synthesized HBV envelope antigens following infection with recombinant vaccinia viruses or transfection with recombinant Epstein-Barr virus expression vectors. Experiments with lysosomotropic agents and brefeldin A suggest that the endosomal compartment is likely involved in the processing of endogenously synthesized viral proteins for recognition by CD4+ T cells. Our study indicates that HBV envelope-specific, HLA class II-restricted CD4+ cytotoxic T lymphocytes can potentially participate in the immune clearance of HBV-infected cells and the pathogenesis of hepatocellular injury in hepatitis B. PMID:1731098

  3. A novel hepatitis B virus (HBV) genetic element with Rev response element-like properties that is essential for expression of HBV gene products.

    PubMed Central

    Huang, J; Liang, T J

    1993-01-01

    Many viruses possess complex mechanisms involving multiple gene products and cis-regulatory elements in order to achieve a fine control of their gene expression at both transcriptional and posttranscriptional levels. Hepatitis B virus (HBV) and retroviruses share many structural and functional similarities. In this study, by genetic and biochemical analyses, we have demonstrated the existence of a novel genetic element within the HBV genome which is essential for high-level expression of viral gene products. This element is located 3' to the envelope coding region. We have shown that this genetic element is cis acting at the posttranscriptional level and that its function is exerted at the level of RNA processing as part of transcribed sequences. This RNA element is also functional in the context of a heterologous gene. Similar to the function of Rev-Rev response element interaction of human immunodeficiency virus type 1, this element appears to inhibit the splicing process and facilitate the transport and utilization of HBV transcripts. Images PMID:8246965

  4. IL6 Inhibits HBV Transcription by Targeting the Epigenetic Control of the Nuclear cccDNA Minichromosome

    PubMed Central

    Palumbo, Gianna Aurora; Scisciani, Cecilia; Pediconi, Natalia; Lupacchini, Leonardo; Alfalate, Dulce; Guerrieri, Francesca; Calvo, Ludovica; Salerno, Debora; Di Cocco, Silvia; Levrero, Massimo; Belloni, Laura

    2015-01-01

    The HBV covalently closed circular DNA (cccDNA) is organized as a mini-chromosome in the nuclei of infected hepatocytes by histone and non-histone proteins. Transcription from the cccDNA of the RNA replicative intermediate termed pre-genome (pgRNA), is the critical step for genome amplification and ultimately determines the rate of HBV replication. Multiple evidences suggest that cccDNA epigenetic modifications, such as histone modifications and DNA methylation, participate in regulating the transcriptional activity of the HBV cccDNA. Inflammatory cytokines (TNFα, LTβ) and the pleiotropic cytokine interleukin-6 (IL6) inhibit hepatitis B virus (HBV) replication and transcription. Here we show, in HepG2 cells transfected with linear HBV monomers and HBV-infected NTCP-HepG2 cells, that IL6 treatment leads to a reduction of cccDNA-bound histone acetylation paralleled by a rapid decrease in 3.5kb/pgRNA and subgenomic HBV RNAs transcription without affecting cccDNA chromatinization or cccDNA levels. IL6 repressive effect on HBV replication is mediated by a loss of HNF1α and HNF4α binding to the cccDNA and a redistribution of STAT3 binding from the cccDNA to IL6 cellular target genes. PMID:26580974

  5. Management of the HBV reactivation in isolated HBcAb positive patients affected with Non Hodgkin Lymphoma

    PubMed Central

    2014-01-01

    Background Occult HBV infection (OBI) is defined by the persistence of HBV in the liver without serum HBsAg and HBVDNA. It represents a life-threatening event during immunosuppressive chemotherapies. An OBI occurs in approximately 18% of HBcAb + patients. International guidelines suggest surveillance for HBV markers in immunosuppressed patients. In Non-Hodgkin Lymphoma (NHL), the prevalence of OBI reactivation remains to be established. Methods In order to determine the prevalence of occult HBV reactivation in a large cohort of patients during chemotherapy for NHL, we analysed 498 NHL patients in a centre of Southern Italy. We evaluated HBV markers, NHL type, treatment type and occurrence of HBV reactivation. Results Forty % of patients were treated with monoclonal antibodies and 60.3% without. Ninety-six patients were HBcAb+, HBsAg-. HBV reactivation occurred in ten subjects of this subgroup. All of them were successfully treated with Lamivudine. None of the patients experienced liver-related death. The prevalence of OBI reactivation was of 10.42% in HBcAb + HBsAb- patients. This event occurred in 50% of patients treated with mild immunosuppressive therapies. Each reactivation was treated with Lamivudine. Discussion This report suggests that a strict surveillance is important and cost-effective in HBcAb + HBsAg- NHL patients treated with mild immunosuppressive therapies, in order to detect an occult HBV reactivation. PMID:24533834

  6. Correlation of the content of hepatitis B core antigen in peripheral blood mononuclear cells with HBV virus load.

    PubMed

    Peng, Yanzhong; Xiong, Xiaojia; Tong, Xindeng; Li, Min; Yang, Xifei; Hu, Guoxin; Geng, Yijie; Li, Jianxin

    2016-06-01

    The dysfunction of peripheral blood mononuclear cell (PBMC) plays an important role in hepatitis B virus (HBV) chronic infection and tolerance. This study is aimed to explore the changes of expression and distribution of Hepatitis B virus core antigen (HBcAg) in the PBMCs of patients infected with chronic hepatitis B virus by using confocal laser scanning microscopy (CLSM). The levels of HBcAg in PBMCs were correlated with the HBV load in serum, and the change of HBcAg distribution in different PBMC organelles may represent various HBV infection states. HBcAg was mainly distributed in the nuclei of PBMC in the cases of immune tolerance and no inflammatory activity. Taken together, our data suggest that the measurement of HBcAg and its distribution in PBMCs using CLSM may serve as an alternative approach to monitor HBV load and the immune states of HBV infection with ease of using and improved sensitivity. PMID:26680298

  7. HBV and HIV co-infection: Impact on liver pathobiology and therapeutic approaches

    PubMed Central

    Parvez, Mohammad Khalid

    2015-01-01

    The consequences of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection on progression of severe liver diseases is a serious public health issue, worldwide. In the co-infection cases, about 90% of HIV-infected population is seropositive for HBV where approximately 5%-40% individuals are chronically infected. In HIV co-infected individuals, liver-related mortality is estimated over 17 times higher than those with HBV mono-infection. The spectrum of HIV-induced liver diseases includes hepatitis, steatohepatitis, endothelialitis, necrosis, granulomatosis, cirrhosis and carcinoma. Moreover, HIV co-infection significantly alters the natural history of hepatitis B, and therefore complicates the disease management. Though several studies have demonstrated impact of HIV proteins on hepatocyte biology, only a few data is available on interactions between HBV and HIV proteins. Thus, the clinical spectrum as well as the complexity of the co-infection offers challenging fronts to study the underlying molecular mechanisms, and to design effective therapeutic strategies. PMID:25625003

  8. Alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV.

    PubMed

    Qin, Yannan; Zhong, Yaogang; Ma, Tianran; Wu, Fei; Wu, Haoxiang; Yu, Hanjie; Huang, Chen; Li, Zheng

    2016-04-01

    The incidence of hepatocellular carcinoma (HCC) is closely correlated with hepatitis B virus (HBV)-induced liver cirrhosis. Structural changes in the glycans of serum and tissue proteins are reliable indicators of liver damage. However, little is known about the alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV infection. This study compared the differential expression of liver glycopatterns in 7 sets of normal pericarcinomatous tissues (PCTs), cirrhotic, and tumor tissues from patients with liver cirrhosis and HCC induced by HBV using lectin microarrays. Fluorescence-based lectin histochemistry and lectin blotting were further utilized to validate and assess the expression and distribution of certain glycans in 9 sets of corresponding liver tissue sections. Eight lectins (e.g., Jacalin and AAL) revealed significant difference in cirrhotic tissues versus PCTs. Eleven lectins (e.g., EEL and SJA) showed significant alteration during cirrhotic and tumor progression. The expression of Galα1-3(Fucα1-2)Gal (EEL) and fucosyltransferase 1 was mainly increasing in the cytoplasm of hepatocytes during PCTs-cirrhotic-tumor tissues progression, while the expression of T antigen (ACA and PNA) was decreased sharply in cytoplasm of tumor hepatocytes. Understanding the precision alteration of liver glycopatterns related to the development of hepatitis, cirrhosis, and tumor induced by HBV infection may help elucidate the molecular mechanisms underlying the progression of chronic liver diseases and develop new antineoplastic therapeutic strategies. PMID:26833199

  9. Modeling and Analyzing the Transmission Dynamics of HBV Epidemic in Xinjiang, China

    PubMed Central

    Zhang, Tailei; Wang, Kai; Zhang, Xueliang

    2015-01-01

    Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV) which affects livers. In this paper, we formulate a hepatitis B model to study the transmission dynamics of hepatitis B in Xinjiang, China. The epidemic model involves an exponential birth rate and vertical transmission. For a better understanding of HBV transmission dynamics, we analyze the dynamic behavior of the model. The modified reproductive number σ is obtained. When σ < 1, the disease-free equilibrium is locally asymptotically stable, when σ > 1, the disease-free equilibrium is unstable and the disease is uniformly persistent. In the simulation, parameters are chosen to fit public data in Xinjiang. The simulation indicates that the cumulated HBV infection number in Xinjiang will attain about 600,000 cases unless there are stronger or more effective control measures by the end of 2017. Sensitive analysis results show that enhancing the vaccination rate for newborns in Xinjiang is very effective to stop the transmission of HBV. Hence, we recommend that all infants in Xinjiang receive the hepatitis B vaccine as soon as possible after birth. PMID:26422614

  10. HIV, HBV and HCV Coinfection Prevalence in Iran - A Systematic Review and Meta-Analysis

    PubMed Central

    Bagheri Amiri, Fahimeh; Mostafavi, Ehsan; Mirzazadeh, Ali

    2016-01-01

    Background worldwide, hepatitis C and B virus infections (HCV and HCV), are the two most common coinfections with human immunodeficiency virus (HIV) and has become a major threat to the survival of HIV-infected persons. The review aimed to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple coinfections in different subpopulations in Iran. Method Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in Iran. We systematically reviewed the literature to identify eligible studies from January 1996 to March 2012 in English or Persian/Farsi databases. We extracted the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot test), HCV antibodies and HBsAg (with confirmatory laboratory test) as the main primary outcome. We reported the prevalence of the three infections and coinfections as point and 95% confidence intervals. Findings HIV prevalence varied from %0.00 (95% CI: 0.00–0.003) in the general population to %17.25 (95% CI: 2.94–31.57) in people who inject drugs (PWID). HBV prevalence ranged from % 0.00 (95% CI: 0.00–7.87) in health care workers to % 30.9 (95% CI: 27.88–33.92) in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00–0.66) in health care workers to %51.46 (95% CI: 34.30–68.62) in PWID. The coinfection of HIV/HBV and also HIV/HCV in the general population and in health care workers was zero, while the most common coinfections were HIV/HCV (10.95%), HIV/HBV (1.88%) and triple infections (1.25%) in PWID. Conclusions We found that PWID are severely and disproportionately affected by HIV and the other two infections, HCV and HBV. Screenings of such coinfections need to be reinforced to prevent new infections and also reduce further transmission in their community and to others. PMID:27031352

  11. Insulin resistance and steatosis in HBV-HCV co-infected patients: Role of PNPLA3 polymorphisms and impact on liver fibrosis progression

    PubMed Central

    Zampino, Rosa; Coppola, Nicola; Cirillo, Grazia; Boemio, Adriana; Minichini, Carmine; Marrone, Aldo; Stanzione, Maria; Starace, Mario; Durante-Mangoni, Emanuele; Sagnelli, Evangelista; Restivo, Luciano; Salzillo, Giovanna; Fascione, Maria Chiara; Nevola, Riccardo; del Giudice, Emanuele Miraglia; Adinolfi, Luigi Elio

    2014-01-01

    AIM: To evaluate steatosis, insulin resistance (IR) and patatin-like phospholipase domain-containing 3 (PNPLA3) and their relation to disease progression in hepatitis B and C viruses (HCV-HBV) co-infected patients. METHODS: Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled: 66 had HBV-HCV, 66 HBV and 198 HCV infection. Prevalence of steatosis, IR and PNPLA3 polymorphisms and their relation to anthropometric, biochemical, virological and histological parameters were evaluated. RESULTS: Prevalence of steatosis in group HBV-HCV was similar to that in HCV (47.0% vs 49.5%, respectively); group HBV showed the lowest steatosis (33.3%). Group HBV-HCV had a lesser degree of steatosis than HCV (P = 0.016), lower HCV RNA levels (P = 0.025) and lower prevalence and degree of IR (P = 0.01). PNPLA3 polymorphisms were associated with steatosis. Group HBV-HCV showed higher levels of liver fibrosis than group HCV (P = 0.001), but similar to that observed in HBV group. In HBV-HCV group, liver fibrosis was not associated with steatosis, IR or PNPLA3. HBV infection was the independent predictor of advanced liver fibrosis. CONCLUSION: HBV-HCV co-infected patients have lower degree of hepatic steatosis, IR and HCV RNA than HCV mono-infected; co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance. PMID:25276284

  12. Baseline characteristics of HIV & hepatitis B virus (HIV/HBV) co-infected patients from Kolkata, India

    PubMed Central

    Sarkar, Jayeeta; Saha, Debraj; Bandyopadhyay, Bhaswati; Saha, Bibhuti; Kedia, Deepika; Guha Mazumder, D.N.; Chakravarty, Runu; Guha, Subhasish Kamal

    2016-01-01

    Background & objectives: Hepatitis B virus (HBV) and HIV co-infection has variable prevalence worldwide. In comparison to HBV mono-infection, the course of chronic HBV infection is accelerated in HIV/HBV co-infected patients. The present study was carried out to analyse the baseline characteristics (clinical, biochemical, serological and virological) of treatment naïve HIV/HBV co-infected and HIV mono-infected patients. Methods: Between July 2011 and January 2013, a total number of 1331 HIV-seropositive treatment naïve individuals, enrolled in the ART Centre of Calcutta School of Tropical Medicine, Kolkata, India, were screened for hepatitis B surface antigen (HBsAg). A total of 1253 HIV mono-infected and 78 HIV/HBV co-infected patients were characterized. The co-infected patients were evaluated for HBeAg and anti-HBe antibody by ELISA. HIV RNA was quantified for all co-infected patients. HBV DNA was detected and quantified by real time-PCR amplification followed by HBV genotype determination. Results: HIV/HBV co-infected patients had proportionately more advanced HIV disease (WHO clinical stage 3 and 4) than HIV mono-infected individuals (37.1 vs. 19.9%). The co-infected patients had significantly higher serum bilirubin, alanine aminotransferase (ALT), alkaline phosphatase and ALT/platelet ratio index (APRI). CD4 count was non-significantly lower in co-infected patients. Majority (61.5%) were HBeAg positive with higher HIV RNA (P<0.05), HBV DNA (P<0.001) and APRI (P<0.05) compared to those who were HBeAg negative. HBV/D was the predominant genotype (73.2%) and D2 (43.7%) was the commonest subgenotype. Interpretation & conclusions: HIV/HBV co-infected patients had significantly higher serum bilirubin, ALT, alkaline phosphatase and lower platelet count. HBeAg positive co-infected patients had higher HIV RNA and HBV DNA compared to HBeAg negative co-infected patients. Prior to initiation of antiretroviral treatment (ART) all patients should be screened for HBsAg to

  13. The Early Results of a New Health Care Program Implementation in HBV Screening: an Iranian Experience

    PubMed Central

    Sharifian, Afsaneh; Naderi, Nostratollah; Sanati, Azar; Mohebi, Seyed Reza; Azimzadeh, Pedram; Golmohamadi, Ali; Nori, Simin; Khanyaghma, Mahsa; Sheikhesmaeili, Farshad; Zali, Mohamad Reza

    2015-01-01

    BACKGROUND According to the reports of World Health Organization (WHO) and Centers for Disease Control and Prevention, the prevalence of chronic hepatitis B infection in Iran has decreased from 2-7% in 2001 to 1.3-0.8% in children aged 2-14 years. In 2010 the Institute of Medicine recommended more comprehensive screening by primary care physicians (PCPs) for evaluation, vaccination, and management of infected patients for further decrease in the prevalence of chronic HBV infection. Thus, with contribution of the Health Department, we developed a practical flowchart for PCPs to start active screening of hepatitis B virus (HBV) in all visited patients and refer the positive cases for further evaluation and management to Taleghani Hospital. METHODS With collaboration of Health Department of Shahid Beheshti University of Medical Sciences), physicians of health centers were asked to screen all their patients for HBsAg. Positive cases were referred to Taleghani Hospital. They were first registered and educated about their disease, life style, and prevention methods. Their first degree families were screened for HBV infection too and were referred for vaccination if needed. According to the results of lab tests, appropriate management was done by a hepatologist. RESULTS Since implementation of this program, we have encountered a significant rise in patient detection (even in high risk groups). Many of them were not aware of their disease and most of those who were aware of their disease were not managed appropriately. Family screening and vaccination were inadequate and need more emphasis. CONCLUSION Although health system is active about screening of HBV infection in high risk populations, it is not perfect. It seems that health system needs to upgrade the screening and management programs of HBV infection. PMID:26609351

  14. Blocking peptides against HBV: PreS1 protein selected from a phage display library

    SciTech Connect

    Wang, Wei; Liu, Yang; Zu, Xiangyang; Jin, Rui; Xiao, Gengfu

    2011-09-09

    Highlights: {yields} Successfully selected specific PreS1-interacting peptides by using phage displayed library. {yields} Alignment of the positive phage clones revealed a consensus PreS1 binding motif. {yields} A highly enriched peptide named P7 had a strong binding ability for PreS1. {yields} P7 could block PreS1 attachment. -- Abstract: The PreS1 protein is present on the outermost part of the hepatitis B virus (HBV) surface and has been shown to have a pivotal function in viral infectivity and assembly. The development of reagents with high affinity and specificity for PreS1 is of great significance for early diagnosis and treatment of HBV infection. A phage display library of dodecapeptide was screened for interactions with purified PreS1 protein. Alignment of the positive phage clones revealed a putative consensus PreS1 binding motif of HX{sub n}HX{sub m}HP/R. Moreover, a peptide named P7 (KHMHWHPPALNT) was highly enriched and occurred with a surprisingly high frequency of 72%. A thermodynamic study revealed that P7 has a higher binding affinity to PreS1 than the other peptides. Furthermore, P7 was able to abrogate the binding of HBV virions to the PreS1 antibody, suggesting that P7 covers key functional sites on the native PreS1 protein. This newly isolated peptide may, therefore, be a new therapeutic candidate for the treatment of HBV. The consensus motif could be modified to deliver imaging, diagnostic, and therapeutic agents to tissues affected by HBV.

  15. The combination of tacrolimus and entecavir improves the remission of HBV-associated glomerulonephritis without enhancing viral replication

    PubMed Central

    Wang, Lifen; Ye, Zhiming; Liang, Huaban; Zhang, Bin; Xu, Lixia; Feng, Zhonglin; Liu, Shuangxin; Shi, Wei

    2016-01-01

    Background: Tacrolimus inhibits hepatitis B virus entry into hepatocytes through targeting the HBV receptor, sodium taurocholate cotransporting polypeptide. This study was performed to evaluate the efficacy and safety of Tacrolimus combined with entecavir antiviral therapy for HBV-associated glomerulonephritis patients with biopsy-proven membranous nephropathy. Method: A cohort of 42 patients was enrolled in this retrospective study. Twenty-three patients received Tacrolimus (0.05 mg/kg/day) in combination entecavir over 24 weeks, whereas the other 19 patients only received entecavir monotherapy. Results: The probability of proteinuria remission in the Tacrolimus+entecavir group was 69 and 87% after 12 and 24 weeks, whereas was only 26 and 42%, respectively, in the entecavir group. The mean time to partial or complete remission was 18.6 weeks in the Tacrolimus+entecavir group and 34.3 weeks in the entecavir group (P<0.001). A decrease in the HBV DNA titer was observed in all patients with active HBV replication. None of the HBV carriers in the Tacrolimus+entecavir group showed evidence of HBV reactivation. The serum creatinine and alanine aminotransferase levels remained stable in both groups. The Tacrolimus target trough concentration was 5-10 ng/mL. Conclusion: Tacrolimus combined with entecavir rapidly and effectively induced remission of HBV-GN in Chinese adults. Furthermore, Tacrolimus may have a synergistic antiviral effect with entecavir.

  16. Leukocyte telomere length-related rs621559 and rs398652 genetic variants influence risk of HBV-related hepatocellular carcinoma.

    PubMed

    Pan, Wenting; Cheng, Guangxia; Xing, Huaixin; Shi, Juan; Lu, Chao; Wei, Jinyu; Li, Lichao; Zhou, Changchun; Yuan, Qipeng; Zhou, Liqing; Yang, Ming

    2014-01-01

    Recent genome-wide association studies (GWAS) have identified eleven leukocyte telomere length (LTL)-related single nucleotide polymorphisms (SNPs). Since LTL has been associated with risk of many malignancies, LTL-related SNPs may contribute to cancer susceptibility. To test this hypothesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we genotyped these eleven LTL-related SNPs in a case-control set including 1186 HBV-related HCC cases, 508 chronic HBV carriers and 1308 healthy controls at the discovery stage. The associations of HCC risk with these SNPs were further confirmed in an independent case-control set. We found that 1p34.2 rs621559 and 14q21 rs398652 were significantly associated with HBV-related HCC risk (both P<0.005 after Bonferroni corrections). There was no significant difference of either rs621559 or rs398652 genotypes between chronic HBV carriers and healthy controls, demonstrating that the association was not due to predisposition to HBV infection. In the pooled analyses (1806 HBV-related HCC cases and 1954 controls), we observed a decreased HCC risk, 0.72-times, associated with the 1p34.2 rs621559 AA genotype compared to the GG genotype (P = 1.6×10(-6)). Additionally, there was an increased HCC risk, 1.27-fold, associated with the rs398652 GG genotype (P = 3.3×10(-6)). A statistical joint effect between the rs621559 GG and rs398652 GG genotypes may exist in elevating risk of HBV-related HCC. We show, for the first time, that rs398652 and rs621559 might be marker genetic variants for risk of HBV-related HCC in the Chinese population. PMID:25365256

  17. Association of TNF-α Promoter Polymorphism with HBV Associated Disease Outcome Among HBV Infected Patients from Orissa, Southern Part of East India

    PubMed Central

    Panigrahi, Rajesh; Sarkar, Neelakshi; Biswas, Avik; Pal, Ananya; Saha, Debraj; Singh, Shivaram P.; Panigrahi, Manas K.; Bandopadhyay, Manikanana; Chakrabarti, Sekhar; Chakravarty, Runu

    2014-01-01

    Background TNF-α promoter polymorphism has been known to be a potential predictive factor in patients with HBV infection. We therefore tried to investigate whether the TNF-α promoter polymorphism at position −238, −857 and −863 was associated with the outcome of HBV infection in a population from Orissa, southern part of East India. Methods A total of 195 patients recruited for the study were classified into 85 controls and 110 HBV infected cases, which included 34 IC, 30 CLD, 32 LC and 14 HCC patients. The polymorphisms at the respective sites were detected by a PCR-RFLP followed by statistical analysis. Results The frequency of the genotype −238 GG and the allele −238G in the cases (89.0% and 92.7% respectively) was significantly higher than that in the controls (68.2% and 82.2% respectively) (P < 0.001, OR = 3.8 and P = 0.001, OR = 2.73). Whereas the −238 GA genotype was significantly high in the control group (28.2%) when compared to the cases (7.2%) (P < 0.001, OR = 0.2). Similarly, the frequency of −863CC and the allele −863C was significantly higher among the cases (24.5% and 49.5%) compared to controls (1.17% and 34.7%), (P < 0.001, OR = 27.32 and P = 0.003, OR = 1.85), whereas the −863CA genotype was significantly high in the controls (67.0%) when compared to the cases (50.0%) (P = 0.01, OR = 0.49). Haplotype −863C/−857C/−238G in cases was significantly higher than controls (P = 0.002). Multivariate logistic regression analysis indicates that the genotype −863CC bears a negative association with liver disease progression. Conclusion The present study established an association of polymorphisms at site −238 and −863 of the TNF-α promoter with the outcome HBV infection and disease progression. PMID:25755561

  18. The angiotensin converting enzyme inhibitory tripeptides Ile-Pro-Pro and Val-Pro-Pro show increasing permeabilities with increasing physiological relevance of absorption models.

    PubMed

    Foltz, Martin; Cerstiaens, Anja; van Meensel, Ans; Mols, Raf; van der Pijl, Pieter C; Duchateau, Guus S M J E; Augustijns, Patrick

    2008-08-01

    Transepithelial transport of the ACE inhibitory peptides Ile-Pro-Pro and Val-Pro-Pro was studied in different models of absorption. Apparent permeability (P(app)) values for absorptive transport across Caco-2 monolayers were 1.0+/-0.9 x 10(-8) (Ile-Pro-Pro) and 0.5+/-0.1 x 10(-8)cms(-1) (Val-Pro-Pro). Ex vivo transport across jejunal segments in the Ussing chamber was 5-times (Ile-Pro-Pro) to 10-times (Val-Pro-Pro) higher with no significant differences (p>0.05) observed between both peptides. The peptidase inhibitor bestatin increased permeability for the absorptive direction for Ile-Pro-Pro by twofold. Neither a transepithelial pH gradient nor increased apical tripeptide concentration nor longitudinal localization of the intestinal segment influenced P(app) in the ex vivo experiments. Val-Pro-Pro transport across Peyer's patches, however, was 4-times higher (P(app)=21.0+/-9.3 x10(-8)cms(-1)) as compared to duodenum (P(app)=4.8+/-1.4 x 10(-8)cms(-1)). In the in situ perfusion experiments P(app) values varied greatly among different animals ranging from 0.5 to 24.0 x10(-8)cms(-1) (Ile-Pro-Pro) and from 1.0 to 15.6 x 10(-8)cms(-1) (Val-Pro-Pro). In summary, Caco-2 and ex vivo absorption models differ considerably regarding their peptide permeability. The in situ model seems to be less appropriate because of the observed large variability in peptide permeability. The results of this study demonstrate that the ACE inhibitory peptides Ile-Pro-Pro and Val-Pro-Pro are absorbed partially undegraded. PMID:18490081

  19. Automated Triplex (HBV, HCV and HIV) NAT Assay Systems for Blood Screening in India

    PubMed Central

    2016-01-01

    This review is confined to triplex nucleic acid testing (NAT) assays to be used on fully automated platform. Around the world, these assays are being used at various transfusion medicine centres or blood banks to screen blood units for HBV, HCV and HIV. These assay systems can screen up to 1000 blood units for HBV, HCV and HIV simultaneously in a day. This area has been dominated by mainly two manufacturers: M/s Gen-Probe-Novartis and M/s Roche Molecular Systems. The triplex NAT assay systems of both manufacturers are licensed by United States Food and Drug Administration. There is not much awareness about the technology and procedures used in these assays. The main objective of this review is to create awareness about the technology and procedure of these assays. PMID:27042485

  20. Automated Triplex (HBV, HCV and HIV) NAT Assay Systems for Blood Screening in India.

    PubMed

    Rajput, Manoj Kumar

    2016-02-01

    This review is confined to triplex nucleic acid testing (NAT) assays to be used on fully automated platform. Around the world, these assays are being used at various transfusion medicine centres or blood banks to screen blood units for HBV, HCV and HIV. These assay systems can screen up to 1000 blood units for HBV, HCV and HIV simultaneously in a day. This area has been dominated by mainly two manufacturers: M/s Gen-Probe-Novartis and M/s Roche Molecular Systems. The triplex NAT assay systems of both manufacturers are licensed by United States Food and Drug Administration. There is not much awareness about the technology and procedures used in these assays. The main objective of this review is to create awareness about the technology and procedure of these assays. PMID:27042485

  1. The Impact of Gender Differences in Attitudes and Beliefs Concerning HBV Vaccination and Screening in the Lao Community.

    PubMed

    Akosionu, Odichinma; Virnig, Beth; Call, Kathleen T; Yuan, Jian-Min; Chanthanouvong, Sunny; Nguyen, Ruby H N

    2016-02-01

    Liver cancer incidence is increasing among Asian Americans. Laotians in the US have greater risk of liver cancer death compared to other Asian American groups. However, ethnicity is not the only disparity; Laotian men are at increased risk of liver cancer compared to Laotian women. Use of hepatitis B virus (HBV) vaccination and screening is low among Laotians. The impact of gender differences in attitudes and beliefs concerning HBV vaccination and screening is unknown. This secondary analysis of a cross-sectional community-based participatory research study. Although men were more likely to believe that infection with HBV is preventable, and treatable, causes liver cancer, and that healthy persons should be vaccinated, of those who thought people should get vaccinated, women were four times more likely to receive vaccine than men (adj. OR 4.0, CI 1.2-19). Understanding and addressing gender differences may increase HBV screening and vaccination uptake, thus reducing disparities within the Laotian community. PMID:25612922

  2. Seroprevalence of HIV, HBV, HCV, and HTLV among Pregnant Women in Southwestern Nigeria.

    PubMed

    Opaleye, Oluyinka Oladele; Igboama, Magdalene C; Ojo, Johnson Adeyemi; Odewale, Gbolabo

    2016-01-01

    Sexually transmitted infections (STIs) are major public health challenge especially in developing countries. This study was designed to determine the prevalence of Hepatitis B virus (HBV), Hepatitis C Virus (HCV), Human immunodeficiency virus (HIV), and Human T-cell lymphotropic Virus type I (HTLV-I) among pregnant women attending antenatal clinic, in Ladoke Akintola University Teaching Hospital, Osogbo, and South-Western Nigeria. One hundred and eighty two randomly selected pregnant women were screened for HBsAg, anti-HCV, anti-HIV and HTLV-1 IgM antibodies using commercially available ELISA kit. Of the 182 blood samples of pregnant women screened whose age ranged from 15-49 years, 13 (7.1%), 5 (2.7%), 9 (4.9%), and 44 (24.2%) were positive for HBsAg, anti-HCV, anti-HIV, and HTLV-1 IgM antibodies, respectively. The co-infection rate of 0.5% was obtained for HBV/HCV, HBV/HIV, HIV/HTLV-1, and HCV/HTLV-1 while 1.1% and 0% was recorded for HBV/HTLV-1 and HCV/HIV co-infections, respectively. Expected risk factors such as history of surgery, circumcision, tattooing and incision showed no significant association with any of the viral STIs (P > 0.05). This study shows that there is the need for a comprehensive screening of all pregnant women for HBsAg, anti-HCV, anti-HIV and HTLV-1 to prevent mother to child transmission of these viral infections and its attending consequences. PMID:25879258

  3. Diagnostic value of serum Golgi protein 73 for HBV-related primary hepatic carcinoma

    PubMed Central

    Gao, Guosheng; Dong, Feibo; Xu, Xiaozhen; Hu, Airong; Hu, Yaoren

    2015-01-01

    Background: Alpha-fetoprotein (AFP) levels are routinely used for diagnosis and monitoring of hepatic diseases, but it has a limited value. Golgi protein 73 (GP73) has been suggested as a new marker for hepatic diseases. Objective: To explore the clinical value of serum GP73 in different diseases associated with hepatitis B virus (HBV) infection. Method: Between January 2010 and August 2014, serum samples from 88 patients with chronic hepatitis B (CHB), 78 patients with HBV-related liver cirrhosis (LC), and 194 patients with HBV-related primary hepatic cancer (PHC) were collected. Serum samples from 30 healthy volunteers were used as controls. ELISA and microparticle enzyme immunoassay were used to measure serum GP73 and AFP levels. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of serum GP73 and AFP for PHC. Results: For the diagnosis of PHC, GP73 showed a sensitivity of 65.5% and specificity of 66.3%, while AFP levels showed sensitivity of 64.4% and specificity of 76.5%. Serial testing (both tests are positive) could increase the specificity (sensitivity of 45.9% and specificity of 85.5%) while parallel testing (any single positive test result) could increase the sensitivity (sensitivity of 84.0% and specificity of 57.2%). Serum GP73 and AFP levels were significantly different between Child-Pugh grades (P<0.001 for GP73 and P=0.044 for AFP). Significant differences in serum GP73 and AFP were found between TNM stages (all P<0.001). Conclusion: Serum GP73 had limited diagnostic value for HBV-related PHC. The combined use of serum GP73 and AFP levels improved the diagnostic efficacy. PMID:26617863

  4. Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections.

    PubMed

    Armitage, Andrew E; Stacey, Andrea R; Giannoulatou, Eleni; Marshall, Elizabeth; Sturges, Pamela; Chatha, Kamaljit; Smith, Nicola M G; Huang, XiaoJie; Xu, XiaoNing; Pasricha, Sant-Rayn; Li, Ning; Wu, Hao; Webster, Craig; Prentice, Andrew M; Pellegrino, Pierre; Williams, Ian; Norris, Phillip J; Drakesmith, Hal; Borrow, Persephone

    2014-08-19

    During HIV type-1 (HIV-1), hepatitis C virus (HCV), and hepatitis B virus (HBV) infections, altered iron balance correlates with morbidity. The liver-produced hormone hepcidin dictates systemic iron homeostasis. We measured hepcidin, iron parameters, cytokines, and inflammatory markers in three cohorts: plasma donors who developed acute HIV-1, HBV, or HCV viremia during the course of donations; HIV-1-positive individuals progressing from early to chronic infection; and chronically HIV-1-infected individuals (receiving antiretroviral therapy or untreated). Hepcidin increased and plasma iron decreased during acute HIV-1 infection, as viremia was initially detected. In patients transitioning from early to chronic HIV-1 infection, hepcidin in the first 60 d of infection positively correlated with the later plasma viral load set-point. Hepcidin remained elevated in individuals with untreated chronic HIV-1 infection and in subjects on ART. In contrast to HIV-1, there was no evidence of hepcidin up-regulation or hypoferremia during the primary viremic phases of HCV or HBV infection; serum iron marginally increased during acute HBV infection. In conclusion, hepcidin induction is part of the pathogenically important systemic inflammatory cascade triggered during HIV-1 infection and may contribute to the establishment and maintenance of viral set-point, which is a strong predictor of progression to AIDS and death. However, distinct patterns of hepcidin and iron regulation occur during different viral infections that have particular tissue tropisms and elicit different systemic inflammatory responses. The hypoferremia of acute infection is therefore a pathogen-specific, not universal, phenomenon. PMID:25092293

  5. Static structures and dynamics of hemoglobin vesicle (HBV) developed as a transfusion alternative.

    PubMed

    Sato, Takaaki; Sakai, Hiromi; Sou, Keitaro; Medebach, Martin; Glatter, Otto; Tsuchida, Eishun

    2009-06-18

    Hemoglobin vesicle (HbV) is an artificial oxygen carrier that encapsulates solution of purified and highly concentrated (ca. 38 g dL(-1)) human hemoglobin. Its exceptionally high concentration as a liposomal product (ca. 40% volume fraction) achieves an oxygen-carrying capacity comparable to that of blood. We use small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS) to investigate the hierarchical structures and dynamics of HbVs in concentrated suspensions. SAXS data revealed unilamellar shell structure and internal density profile of the artificial cell membrane for Hb encapsulation. The SAXS intensity of HbV at scattering vector q > 0.5 nm(-1) manifests dissolution states of the encapsulated Hbs in the inner aqueous phase of the vesicle having ca. 240 nm diameter. The peak position as well as the height and width of static structure factor of Hb before and after encapsulation are almost identical, demonstrating the preserved protein-protein interactions in the confined space. To overcome multiple scattering from turbid samples, we employed thin layer-cell DLS combined with the so-called bruteforce and echo techniques, which allows us to observe collective diffusion dynamics of HbVs without dilution. A pronounced slowdown of the HbV diffusion and eventual emergence of dynamically arrested state in the presence of high-concentration plasma substitutes (water-soluble polymers), such as dextran, modified fluid gelatin, and hydroxylethyl starch, can be explained by depletion interaction. A significantly weaker effect of recombinant human serum albumin on HbV flocculation and viscosity enhancement than those induced by other polymers is clearly attributed to the specificity as a protein; its compact structure efficiently reduces the reservoir polymer volume fraction that determines the depth of the attractive potential between HbVs. These phenomena are technically essential for controlling the suspension rheology, which is advantageous for versatile

  6. HBV-Related Health Behaviors in a Socio-Cultural Context: Perspectives from Khmers and Koreans

    PubMed Central

    Lee, Haeok; Kiang, Peter; Chea, Phala; Peou, Sonith; Tang, Shirley S.; Yang, JinHwang; Fawcett, Jacqueline; Hann, Hie-Won

    2014-01-01

    Purpose To explore factors influencing health and health care within the sociocultural context of Cambodian Americans (CAs or Khmers) and Korean Americans (KA) and to examine intergroup similarities and differences between CAs and KAs, focusing on hepatitis B virus (HBV) and liver cancer prevention behaviors. Methods The study used a qualitative design guided by the revised Network Episode Model (NEM) and informed by ethnographic analysis. Focus group interviews with key informants among CA community health leaders (CHLs, n=14) and individual interviews with key informants of KA CHLs (n=9) were audiotaped and transcribed. Results Three categories that influenced HBV and liver cancer prevention emerged from both CAs and KAs: the socio-cultural, individual, and behavioral. Four additional sub-categories (sub-themes) of sociocultural were identified as socio-history, socio-medicine, socio-linguistic, and socio-health resources. Both CAs and KAs, however, have low levels of knowledge and significant misunderstandings about HBV infection. Conclusions The study identifies and compares the social-cultural determinant for HBV and liver cancer and highlights the factors of education, intercultural communication, and interactions within socio-cultural contexts of CA and KA subgroups. In general, conceptual overlaps are apparent between Khmers (from now on, the terms, CA and Khmer, will be used interchangeably) and Koreans except for the sub-theme of socio-history. However, differences in concept-specific attributes point to the need to account for differing conceptualizations and implications of specific ethnic groups’ sociocultural contexts, and to design contextually-relevant outreach and educational interventions for targeted AAPI subgroups. PMID:24355416

  7. Hyperoside nanocrystals for HBV treatment: process optimization, in vitro and in vivo evaluation.

    PubMed

    Shen, Baode; Wu, Na; Shen, Chengying; Zhang, Fucheng; Wu, Yan; Xu, Pinghua; Zhang, Lihong; Wu, Wei; Lu, Yi; Han, Jin; Wang, Yonggang; Yuan, Hailong

    2016-11-01

    The aim of this study was to develop hyperoside (Hyp) nanocrystals to enhance its dissolution rate, oral bioavailability and anti-HBV activity. Hyp nanocrystals were prepared using high pressure homogenization technique followed by lyophilization. A Box-Behnken design approach was employed for process optimization. The physicochemical properties, pharmacokinetics and anti-HBV activity in vivo of Hyp nanocrystal prepared with the optimized formulation were systematically investigated. Hyp nanocrystals prepared with the optimized formulation was found to be rod shaped with particle size of 384 ± 21 nm and PDI of 0.172 ± 0.027. XRPD studies suggested slight crystalline change in drug. Dissolution rate obtained from Hyp nanocrystals were markedly higher than pure Hyp. The nanocrystals exhibited enhanced Cmax (7.42 ± 0.73 versus 3.80 ± 0.66 mg/L) and AUC0 - t (193.61 ± 16.30 versus 91.92 ± 17.95 mg·h/L) with a 210.63% increase in relative bioavailability. Hyp nanocrystals exhibited significantly greater anti-HBV activity than Hyp. These results suggested that the developed nanocrystals formulation had a great potential as a viable approach to enhance the bioavailability of Hyp. PMID:27032257

  8. Immune memory responses to HBV vaccine 13-18 years after primary vaccination.

    PubMed

    Hou, L; Li, W; Wei, X; Zhou, Y; Zhuo, Y; Wu, H; Shen, B

    2015-01-01

    The aim of this study was to evaluate the immune memory response 13-18 years after an hepatitis B virus (HBV) vaccine by performing a specific in vitro stimulation experiment. Thirty healthy volunteers who had been inoculated 13-18 years ago with the HBV vaccine were collected from the physical examination center. Peripheral blood mononuclear cells were stimulated with 50 ng/mL recombinant HBsAg. An ELISA kit was used for the detection of antibodies that were produced by these cells in vitro. It was found that even 13-18 years after inoculation with the HBV vaccine, an anamnestic antibody response still existed, and was not correlated with the serum antibody levels (r = -0.177, P = 0.377). In conclusion, our data showed that the individuals after inoculation, including those with anti-HBs <10 IU/L as well as those individuals in whom the antibody was not detected, retained immune memory, which may be the main role of memory B cells. PMID:26345774

  9. NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

    PubMed Central

    Sun, Cheng; Sun, Haoyu; Zhang, Cai; Tian, Zhigang

    2015-01-01

    Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus (HBV) infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer (NK) cells express a large number of immune recognition receptors (NK receptors (NKRs)) to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono- and combination therapeutic strategies that target the NK cell receptor–ligand system may potentially lead to successful and effective immunotherapy in HCC. PMID:25308752

  10. Backpack Smarts from A Pro

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160665.html Backpack Smarts From a Pro Overloaded carryalls injure thousands ... SATURDAY, Aug. 27, 2016 (HealthDay News) -- Ill-fitting backpacks may put school children at risk for muscle ...

  11. Construction of HBV-specific ribozyme and its recombinant with HDV and their cleavage activity in vitro

    PubMed Central

    Wen, Shu-Juan; Xiang, Kai-Jun; Huang, Zhen-Hua; Zhou, Rong; Qi, Xue-Zhong

    2000-01-01

    AIM: To construct the recombinant of HDV cDNA and HBV-specific ribozyme gene by recombinant PCR in order to use HDV as a transporting vector carrying HBV-specific ribozyme into liver cells for inhibiting the replication of HBV. METHODS: We separately cloned the ribozyme (RZ) gene and recombinant DVRZ (comprising HDV cDNA and HBV-specific ribozyme gene) into the downstream of T7 promoter of pTAdv-T vector and studied the in vitro cleavage activity of their transcripts (rRZ, rDVRZ) on target RNA (rBVCF) from in vitro transcription of HBV C gene fragment(BVCF). RESULTS: Both the simple (rRZ) and the recombinant ribozyme rDVRZ could efficiently catalyze the cleavage of target RNA (rBVCF) under different temperatures (37 °C, 42 °C and 55 °C) and Mg2+ concentrations (10 mmol/L, 15 mmol/L and 20 mmol/L) and their catalytic activity tended to increase as the temperature was rising. But the activity of rRZ was evidently higher than that of rDVRZ. CONCLUSION: The recombinant of HDV cDNA and ribozyme gene had the potential of being further explored and used in gene therapy of HBV infection. PMID:11819602

  12. Tumor-infiltrating lymphocyte activity is enhanced in tumors with low IL-10 production in HBV-induced hepatocellular carcinoma

    SciTech Connect

    Shi, Yang Song, Qingwei; Hu, Dianhe; Zhuang, Xiaohu; Yu, Shengcai

    2015-05-22

    Hepatocellular carcinoma (HCC) is one of the most common cancers and can be induced by chronic HBV infection. The role of HBV-specific immune responses in mediating tumorigenesis and HCC prognosis is debated. The effect of intratumoral microenvironment on tumor-infiltrating lymphocytes (TILs) is also unclear. Here, we examined resected tumor tissue from 36 patients with HBV-induced HCC. We categorized study cohort based on ex vivo IL-10 secretion by tumor cells into high IL-10-secreting (Hi10) and low IL-10-secreting (Lo10) groups, and found that the Lo10 group was less sensitive to TLR ligand stimulation. TILs from the Lo10 group contained higher frequencies of HBV-specific IFN-g-producing cells and total IFN-g-producing cells, and possessed higher proliferative capacity. Moreover, the proliferative capacity of TILs from the Hi10 group was negatively correlated with IL-10 secretion from tumor cells. Together, our data demonstrated that low IL-10-producing capacity in HBV-induced HCC tumors is associated with enhanced TIL activity. - Highlights: • We examined intratumoral IL-10 production in HBV-induced HCC. • We grouped HCC tumors into Hi10 and Lo10 groups based on their IL-10 production. • Lo10 groups had better IFN-g response by TILs. • Lo10 groups had better TIL proliferative capacity. • Lo10 group tumor cells were refractory to TLR ligand stimulation.

  13. Efficacy Comparison of Tenofovir and Entecavir in HBeAg-Positive Chronic Hepatitis B Patients with High HBV DNA

    PubMed Central

    Shi, Hong; Huang, Mingxing; Lin, Guoli; Li, Xiangyong; Wu, Yuankai; Jie, Yusheng

    2016-01-01

    Objectives. To compare entecavir (ETV) and tenofovir disoproxil fumarate (TDF) effects in chronic hepatitis B (CHB) patients with high HBV DNA. Method. 96 patients treated initially with tenofovir (TDF group) or entecavir (ETV group) were included in this retrospective study. The following parameters were assessed: HBeAg and hepatitis B e antibody (anti-HBe) status, serum alanine aminotransferase (ALT), and HBV-DNA levels at weeks 4, 12, 24, 36, 48, 60, 72, and 96; time to ALT normalization, undetectable HBV-DNA levels, and HBeAg seroconversion; total duration of follow-up and adverse reactions. Results. The patients included 66 (69%) and 30 (31%) individuals administered ETV and TDF, respectively, comprising 75% males. They were 35.1 ± 4.5 and 33.7 ± 4.6 years old in ETV and TDF groups, respectively. At 36 weeks, the response rate was significantly higher in the TDF group than in ETV treated patients (90% versus 69.7%, p = 0.03). At 48 weeks, less patients administered ETV showed undetectable HBV-DNA levels compared with the TDF group (86.4% versus 96.7%), a non-statistically significant difference (p = 0.13). Only 1 ETV treated patient developed virological breakthrough at 48–96 w. No adverse reactions were found. Conclusion. ETV and TDF are comparable in efficacy and safety to suppress HBV-DNA replication in HBeAg-positive CHB patients with high HBV DNA. PMID:27034945

  14. Characterization of Treatment-Naive HIV/HBV Co-Infected Patients Attending ART Clinic of a Tertiary Healthcare Centre in Eastern India

    PubMed Central

    Biswas, Avik; Panigrahi, Rajesh; Sarkar, Neelakshi; Sarkar, Jayeeta; Pal, Manisha; Guha, Subhasish Kamal; Saha, Bibhuti; Chakrabarti, Sekhar; Chakravarty, Runu

    2013-01-01

    Objective The study was designed to assess the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection scenario among the human immunodeficiency virus (HIV) infected patients attending a tertiary healthcare unit in eastern India. Additionally, clinical and virological characterization of these viruses, prior to antiretroviral therapy (ART) initiation was also done for better understanding of the disease profile. Methods Pool of ART-naive HIV/HBV co-infected and HIV mono-infected patients, participating in two different studies, were included in this study. HBV DNA was detected by nested-PCR amplification followed by HBV genotype determination and HBV reverse transcriptase (RT) region amplification and direct sequencing for detecting drug resistance. Results The prevalence of HBsAg (11.3%) was higher compared to anti-HCV (1.9%) among the HIV infected ART-naive patients. Moreover, majority of the HBeAg positive HIV/HBV co-infected patients (87.7%) had HBV DNA ≥20,000 IU/ml with median HBV DNA significantly higher than that of HBeAg negative subjects (5.7 log10 IU/ml vs. 4.2 log10 IU/ml; p<0.0001). Multivariate analysis also showed that HBeAg-positive status was independently associated with higher HBV DNA level (p = <0.001). Notably, 60.9% of the HBeAg negative co-infected subjects had HBV DNA ≥2,000 IU/ml of which 37.0% had HBV DNA ≥20,000 IU/ml. Genotype HBV/D (68.2%) was the predominant genotype followed by HBV/A (24.3%) and HBV/C (7.5%). Anti-HBV drug resistant mutations were detected in two (3.8%) of the ART-naive patients. Conclusion The prevalence of HIV/HBV co-infection was relatively higher in our study subjects. HBeAg testing might provide clue for early treatment initiation. Furthermore, HBeAg negative patients are also associated with high HBV DNA levels and therefore require appropriate medical attention. Pre-treatment screening for anti-HBV drug resistant mutations is not necessary before ART initiation. PMID:24023688

  15. Antihepatitis B virus activity of a protein-enriched fraction from housefly (Musca domestica) in a stable HBV-producing cell line.

    PubMed

    Lu, Xuemei; Jin, Xiaobao; Wang, Jie; Chu, Fujiang; Zhu, Jiayong

    2014-01-01

    Hepatitis B virus (HBV) infection remains a major public health problem. Although several vaccines and therapeutic strategies are currently being implemented to combat HBV virus, effective antiviral therapy against HBV infection has not been fully developed. Alternative strategies and new drugs to combat this disease are urged. Insects and insect derivatives are a large and unexploited source of potentially useful compounds for modern medicine. In the present study, we investigated the first anti-HBV activity of a protein-enriched fraction (PE) from the larvae of the housefly (Musca domestica) in a stable HBV-producing cell line. HBsAg and HBeAg in the culture medium were measured by enzyme-linked immunosorbent assay. HBV-DNA was quantified by fluorescent quantification PCR. HBV core protein was assayed by immunofluorescent staining. Results indicate PE treatment inhibited both HBsAg, HBeAg secretion, and HBV-DNA replication. Furthermore, PE could also suppress HBV core protein expression. PE could be a potential candidate for the development of a novel and effective drug for the treatment of HBV infection. PMID:25050391

  16. Antihepatitis B Virus Activity of a Protein-Enriched Fraction from Housefly (Musca domestica) in a Stable HBV-Producing Cell Line

    PubMed Central

    Chu, Fujiang; Zhu, Jiayong

    2014-01-01

    Hepatitis B virus (HBV) infection remains a major public health problem. Although several vaccines and therapeutic strategies are currently being implemented to combat HBV virus, effective antiviral therapy against HBV infection has not been fully developed. Alternative strategies and new drugs to combat this disease are urged. Insects and insect derivatives are a large and unexploited source of potentially useful compounds for modern medicine. In the present study, we investigated the first anti-HBV activity of a protein-enriched fraction (PE) from the larvae of the housefly (Musca domestica) in a stable HBV-producing cell line. HBsAg and HBeAg in the culture medium were measured by enzyme-linked immunosorbent assay. HBV-DNA was quantified by fluorescent quantification PCR. HBV core protein was assayed by immunofluorescent staining. Results indicate PE treatment inhibited both HBsAg, HBeAg secretion, and HBV-DNA replication. Furthermore, PE could also suppress HBV core protein expression. PE could be a potential candidate for the development of a novel and effective drug for the treatment of HBV infection. PMID:25050391

  17. Watershed Modeling of Nutrient Transport Covering the Country of Sweden - Scale Transfer in HBV-NP

    NASA Astrophysics Data System (ADS)

    Arheimer, B.; Andersson, L.

    2002-12-01

    Eutrophication of the Baltic Sea and its coastal zone is considered a serious environmental problem. The problems are mainly caused by excessive load of nitrogen (N) and phosphorus (P). To improve the situation new policies including watershed-based water management are implemented. However, this also demands watershed-based knowledge of nutrient transport proc-esses and appropriate tools for landscape planning. A watershed model (HBV-NP) that can be applied both on the local and the national scale has thus been developed to be used both for international reporting and scenario estimates for more efficient nutrient control strategies. The P part is presently developed within the Swedish Water Management Research Program (VASTRA), in which HBV-NP will be used for evaluation of best management practices, and for communication with local stake-holders. The model has recently been applied at the national scale for calculations of flow-normalized annual average of gross load, N retention and net transport, and source apportionment of the N load reaching the sea. In this application (called TRK) several submodels with different levels of process descriptions were linked together. Dynamic and detailed models were included for arable leaching (SOIL-N model), rainfall interpolation, atmospheric deposition (MATCH model), water balance (HBV), and nutrient transformation in groundwater, rivers and lakes (HBV-N). Based on landscape information in GIS, different leaching rates and emissions were assigned to the water discharge from similar landscape elements in 1000 subbasins covering Sweden. Scale transfer was mainly achieved through up-scaling procedures and by using the conceptual model approach for watershed hydrology, including variability parameters that are calibrated for regions. The modeled river flow and N concentrations were validated against time-series from several independent-monitoring stations. A similar national system is now under development for P, including

  18. Liver Fibrosis Regression Measured by Transient Elastography in Human Immunodeficiency Virus (HIV)-Hepatitis B Virus (HBV)-Coinfected Individuals on Long-Term HBV-Active Combination Antiretroviral Therapy

    PubMed Central

    Audsley, Jennifer; Robson, Christopher; Aitchison, Stacey; Matthews, Gail V.; Iser, David; Sasadeusz, Joe; Lewin, Sharon R.

    2016-01-01

    Background. Advanced fibrosis occurs more commonly in human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected individuals; therefore, fibrosis monitoring is important in this population. However, transient elastography (TE) data in HIV-HBV coinfection are lacking. We aimed to assess liver fibrosis using TE in a cross-sectional study of HIV-HBV coinfected individuals receiving combination HBV-active (lamivudine and/or tenofovir/tenofovir-emtricitabine) antiretroviral therapy, identify factors associated with advanced fibrosis, and examine change in fibrosis in those with >1 TE assessment. Methods. We assessed liver fibrosis in 70 HIV-HBV coinfected individuals on HBV-active combination antiretroviral therapy (cART). Change in fibrosis over time was examined in a subset with more than 1 TE result (n = 49). Clinical and laboratory variables at the time of the first TE were collected, and associations with advanced fibrosis (≥F3, Metavir scoring system) and fibrosis regression (of least 1 stage) were examined. Results. The majority of the cohort (64%) had mild to moderate fibrosis at the time of the first TE, and we identified alanine transaminase, platelets, and detectable HIV ribonucleic acid as associated with advanced liver fibrosis. Alanine transaminase and platelets remained independently advanced in multivariate modeling. More than 28% of those with >1 TE subsequently showed liver fibrosis regression, and higher baseline HBV deoxyribonucleic acid was associated with regression. Prevalence of advanced fibrosis (≥F3) decreased 12.3% (32.7%–20.4%) over a median of 31 months. Conclusions. The observed fibrosis regression in this group supports the beneficial effects of cART on liver stiffness. It would be important to study a larger group of individuals with more advanced fibrosis to more definitively assess factors associated with liver fibrosis regression. PMID:27006960

  19. Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8+ T cell responses against a HBV DNA vaccine in mice.

    PubMed

    Wu, Bing; Zou, Qiang; Hu, Yanxin; Wang, Bin

    2013-10-01

    Interleukin-22 (IL-22) is mainly produced by activated Th1 cells, Th17 cells and NK cells and promotes anti-microbial defense, pro-inflammatory and tissue remodeling responses. However, its potential use as a vaccine adjuvant has not been tested. In this study, we tested if a DNA construct expressing IL-22 (pVAX-IL-22) could be used as a molecular adjuvant to enhance host immune responses induced by HBV DNA vaccination (pcD-S2). After immunizing mice with pcD-S2 combined with pVAX-IL-22, we didn't find enhancement of HBsAg-specific antibody responses in comparison to mice immunized with pcD-S2 alone. However, there was an enhancement of the level of IL-17 expression in antigen specific CD8(+) cytotoxic T lymphocytes (Tc17). By using CD8 T-cell knockout (KO) and IL-17 KO mice, Tc17 cells were found to be a dominant population driving cytotoxicity. Importantly, there was a correlation between pVAX-IL-22 enhancement of T lymphocytes and a reduction of HBsAg-positive hepatocytes in HBsAg transgenic mice. These results demonstrate that IL-22 might be used as an effective adjuvant to enhance cellular immune responses during HBsAg DNA vaccination since it can induce Tc17 cells to break tolerance in HBsAg transgenic mice. PMID:23941891

  20. Lentiviral vector encoding ubiquitinated hepatitis B core antigen induces potent cellular immune responses and therapeutic immunity in HBV transgenic mice.

    PubMed

    Dai, Shenglan; Zhuo, Meng; Song, Linlin; Chen, Xiaohua; Yu, Yongsheng; Zang, Guoqing; Tang, Zhenghao

    2016-07-01

    Predominant T helper cell type 1 (Th1) immune responses accompanied by boosted HBV-specific cytotoxic T lymphocyte (CTL) activity are essential for the clearance of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients. Ubiquitin (Ub) serves as a signal for the target protein to be recognized and degraded through the ubiquitin-proteasome system (UPS). Ubiquitinated hepatitis B core antigen (Ub-HBcAg) has been proved to be efficiently degraded into the peptides, which can be presented by major histocompatibility complex (MHC) class I resulting in stimulating cell-mediated responses. In the present study, lentiviral vectors encoding Ub-HBcAg (LV-Ub-HBcAg) were designed and constructed as a therapeutic vaccine for immunotherapy. HBcAg-specific cellular immune responses and anti-viral effects induced by LV-Ub-HBcAg were evaluated in HBV transgenic mice. We demonstrated that immunization with LV-Ub-HBcAg promoted the secretion of cytokines interleukin-2 (IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), generated remarkably high percentages of IFN-γ-secreting CD8(+) T cells and CD4(+) T cells, and enhanced HBcAg-specific CTL activity in HBV transgenic mice. More importantly, vaccination with LV-Ub-HBcAg could efficiently decreased the levels of serum hepatitis B surface antigen (HBsAg), HBV DNA and the expression of HBsAg and HBcAg in liver tissues of HBV transgenic mice. In addition, LV-Ub-HBcAg could upregulate the expression of T cell-specific T-box transcription factor (T-bet) and downregulate the expression of GATA-binding protein 3 (GATA-3) in spleen T lymphocytes. The therapeutic vaccine LV-Ub-HBcAg could break immune tolerance, and induce potent HBcAg specific cellular immune responses and therapeutic effects in HBV transgenic mice. PMID:26874581

  1. An in-house real-time polymerase chain reaction: standardisation and comparison with the Cobas Amplicor HBV monitor and Cobas AmpliPrep/Cobas TaqMan HBV tests for the quantification of hepatitis B virus DNA

    PubMed Central

    Santos, Ana Paula de Torres; Levi, José Eduardo; Lemos, Marcilio Figueiredo; Calux, Samira Julien; Oba, Isabel Takano; Moreira, Regina Célia

    2016-01-01

    This study aimed to standardise an in-house real-time polymerase chain reaction (rtPCR) to allow quantification of hepatitis B virus (HBV) DNA in serum or plasma samples, and to compare this method with two commercial assays, the Cobas Amplicor HBV monitor and the Cobas AmpliPrep/Cobas TaqMan HBV test. Samples from 397 patients from the state of São Paulo were analysed by all three methods. Fifty-two samples were from patients who were human immunodeficiency virus and hepatitis C virus positive, but HBV negative. Genotypes were characterised, and the viral load was measure in each sample. The in-house rtPCR showed an excellent success rate compared with commercial tests; inter-assay and intra-assay coefficients correlated with commercial tests (r = 0.96 and r = 0.913, p < 0.001) and the in-house test showed no genotype-dependent differences in detection and quantification rates. The in-house assay tested in this study could be used for screening and quantifying HBV DNA in order to monitor patients during therapy. PMID:26872342

  2. ProC: Process Coordinator

    NASA Astrophysics Data System (ADS)

    Hovest, Wolfgang; Knoche, Jörg; Hell, Reinhard; Doerl, Uwe; Riller, Thomas; Matthai, Frank; Ensslin, Torsten; Rachen, Jörg; Robbers, Georg; Adorf, Hans-Martin; Reinecke, Martin; Bartelmann, Matthias

    2016-01-01

    ProC (short for Process Coordinator) is a versatile workflow engine that allows the user to build, run and manage workflows with just a few clicks. It automatically documents every processing step, making every modification to data reproducible. ProC provides a graphical user interface for constructing complex data processing workflows out of a given set of computer programs. The user can, for example, specify that only data products which are affected by a change in the input data are updated selectively, avoiding unnecessary computations. The ProC suite is flexible and satisfies basic needs of data processing centers that have to be able to restructure their data processing along with the development of a project.

  3. TP53 Mutations and HBX Status Analysis in Hepatocellular Carcinomas from Iran: Evidence for Lack of Association between HBV Genotype D and TP53 R249S Mutations

    PubMed Central

    Abedi-Ardekani, Behnoush; Gouas, Doriane; Villar, Stephanie; Sotoudeh, Masoud; Hainaut, Pierre

    2011-01-01

    High incidence of HCC is mostly due to the combination of two major risk factors, chronic infection with hepatitis B (HBV) and/or C (HCV) viruses and exposure to the mycotoxin aflatoxin B1, which induces a particular mutation at codon 249 in TP53 (R249S). Eight genotypes of HBV are diversely found in high and low incidence areas. Regardless of documented strong associations between TP53 R249S mutation and HBV genotypes B, C, A or E, there is no report of such association for genotype D despite of the presence of aflatoxin in areas with high prevalence of HBV genotype D. In Iran, 3% of the population is chronically infected with HBV, predominantly genotype D. Twenty-one histologically confirmed HCC cases from Iran were analyzed for TP53 R249S and HBV double mutations 1762T/1764A, hallmarks of more pathogenic forms of HBV. We did not detect any of these mutations. In addition, we report the only case identified so far carrying both R249S mutation and chronic HBV genotype D, a patient from The Gambia in West Africa. This paper suggests that association between HBV genotype D and aflatoxin-induced TP53 mutation is uncommon, explaining the relatively lower incidence of HCC in areas where genotype D is highly prevalent. PMID:21869931

  4. Anti-virus prophylaxis withdrawal may be feasible in liver transplant recipients whose serum HBeAg and HBV DNA are negative.

    PubMed

    Geng, Lei; Lin, Bing-Yi; Shen, Tian; Guo, Hua; Ye, Yu-Fu; Zheng, Shu-Sen

    2016-06-01

    Anti-virus prophylactic therapy may be not necessary for the prevention of hepatitis B virus (HBV) recurrence after HBV-related liver transplantation (LT). However, studies on completely stopping the hepatitis B immune globulin (HBIG) and nucleos(t)ide analogs (NUC) after LT are few. The aim of the current study was to evaluate the safety of anti-virus prophylaxis withdrawal in liver recipients whose serum hepatitis B e antigen (HBeAg) and HBV DNA are negative. We analyzed 190 patients undergone LT for HBV-related liver disease from 2006 to 2012 and found that 10 patients completely stopped the HBIG and NUC due to poor compliance. These patients were liver biopsied and checked monthly with serum HBV markers, HBV DNA and liver function. Among the 10 patients, 9 did not show the signs of HBV recurrence after a mean follow-up of 51.6 months (range 20-73) after withdrawal of the HBIG and NUC. The average time from LT to the withdrawal of the anti-virus drug was 23.8 (13-42) months; one patient showed hepatitis B surface antigen-positive and detectable HBV DNA after stopping anti-virus drugs and this patient was successfully treated with entecavir. Our data suggested that complete withdrawal of anti-virus prophylaxis was safe and feasible for patients whose serum HBeAg and HBV DNA were negative at the time of LT. PMID:27298109

  5. The HBV spatially distributed flash flood forecasting model - The Slovenia case study

    NASA Astrophysics Data System (ADS)

    Tsanis, I. K.; Grillakis, M. G.; Blöschl, G.; Pogačnik, N.

    2009-04-01

    The HBV distributed flash flood forecasting model which is in operational use in northern Austria is applied to a watershed in northwest Slovenia, a case study for the FP6 project HYDRATE. The selected watershed consists of 6 sub-basins with a total area of 646 Km2. Model setup and calibration was performed in this watershed and three long duration rainfall - runoff periods were simulated in order to examine the efficiency of the model. The selected periods included rainfall events that produced high outflows on the exit of the watershed, such as the September 2007 event that caused a flash flooding and severe damages to the towns of Zali Log and Zelezniki. The model uses 1km grid rainfall and temperature data of fifteen minute time intervals in order to simulate the rainfall - runoff process. Inverse distance weighting interpolation is used in order to generate the spatially distributed rainfall and temperature while the hydrological parameters are defined for each 1km grid cell that correspond to one hydrological response units (HRU - areas with analogous hydrogeological characteristics). The basic calibration of the HBV model is based on hydrological parameters of each HRU, parameters that control the rainfall - runoff process within the basin and non HRU parameters that control the river routing between the basins. The model performance is based on seven efficiency criteria that were selected as appropriate for long simulation periods, e.g. coefficient of determination R2 and Nash Sutcliffe efficiency E. The HBV model produced satisfactory results for the three rainfall periods and could be used as an operational model in Slovenia as well.

  6. The influence of HBV model calibration on flood predictions for future climate

    NASA Astrophysics Data System (ADS)

    Osuch, Marzena; Romanowicz, Renata

    2014-05-01

    The temporal variability of HBV rainfall-runoff model parameters was tested to address the influence of climate characteristics on the values of model optimal parameters. HBV is a conceptual model with a physically-based structure that takes into account soil moisture, snow-melt and dynamic runoff components. The model parameters were optimized by the DEGL method (Differential Evolution with Global and Local neighbours) for a set of catchments located in Poland. The methodology consisted of the calibration and cross-validation of the HBV models on a series of five-year periods within a moving window. The optimal parameter values show large temporal variability and dependence on climatic conditions described by the mean and standard deviation of precipitation, air temperature and PET. Derived regressions models between parameters and climatic indices were statistically significant at the 0.05 level. The set of model optimal values was applied to simulate future flows in a changed climate. We used the precipitation and temperature series from 6 RCM/GCM models for 2071-2100 following the A1B climate change scenario. The climatic variables were obtained from the KLIMADA project. The resulting flow series for the future climate scenario were used to derive flow indices, including the flood quantiles. Results indicate a large influence of climatic variability on flow indices. This work was partly supported by the project "Stochastic flood forecasting system (The River Vistula reach from Zawichost to Warsaw)" carried out by the Institute of Geophysics, Polish Academy of Sciences by order of the National Science Centre (contract No. 2011/01/B/ST10/06866). The rainfall and flow data were provided by the Institute of Meteorology and Water Management (IMGW), Poland.

  7. Diagnostic and therapeutic progress of multi-drug resistance with anti-HBV nucleos(t)ide analogues

    PubMed Central

    Song, Zhuo-Lun; Cui, Yu-Jun; Zheng, Wei-Ping; Teng, Da-Hong; Zheng, Hong

    2012-01-01

    Nucleos(t)ide analogues (NA) are a breakthrough in the treatment and management of chronic hepatitis B. NA could suppress the replication of hepatitis B virus (HBV) and control the progression of the disease. However, drug resistance caused by their long-term use becomes a practical problem, which influences the long-term outcomes in patients. Liver transplantation is the only choice for patients with HBV-related end-stage liver disease. But, the recurrence of HBV after transplantation often caused by the development of drug resistance leads to unfavorable outcomes for the recipients. Recently, the multi-drug resistance (MDR) has become a common issue raised due to the development and clinical application of a variety of NA. This may complicate the antiviral therapy and bring poorly prognostic outcomes. Although clinical evidence has suggested that combination therapy with different NA could effectively reduce the viral load in patients with MDR, the advent of new antiviral agents with high potency and high genetic barrier to resistance brings hope to antiviral therapy. The future of HBV researches relies on how to prevent the MDR occurrence and develop reasonable and effective treatment strategies. This review focuses on the diagnostic and therapeutic progress in MDR caused by the anti-HBV NA and describes some new research progress in this field. PMID:23326119

  8. Recombinant HBV vaccine enhances the rate of sustained virological response when early initiated after anti-HCV combination therapy.

    PubMed

    Hanafy, Amr Shaaban; Farag, Alaa Ahmad; Hassanin, Hassan Mahmoud; Hassaneen, Ahmad Mahmoud

    2016-01-01

    The overall SVR rate for chronic hepatitis C genotype 4 using the Standard of care is 54.3%. HBV infection can be prevented by the administration of effective and safe vaccine. Evaluation of the vaccination-induced anti-HBs response rates in a cohort of HCV Egyptian patients after being exposed to antiviral combination therapy and the magnitude of its effect on the rate of SVR through its putative role in induction of crossed immunity. (A) 500 HCV patients who had completed the course of antiviral therapy and achieved ETR were retrospectively analyzed and received 20 μg of recombinant DNA vaccine for hepatitis B at time intervals (0, 1, and 4 months). The first dose of the vaccine was initiated one month post treatment. (B) Laboratory analysis: Included routine preliminary investigations to anti viral therapy and specific investigations as determination of anti-HBs antibodies 2 months following the third dose of vaccine. 433 patients showed protective response (86.6%), 67 patients were non-responders (13.4%) (P = 0.003). Adding HBV vaccine 1 month post-treatment increased SVR (400 patients, 80%) (χ(2)  = 40.3, P = 0.000). Diabetes affect response to HBV vaccine (P = 0.0001). Adding HBV vaccine to the post treatment care of patients with HCV after termination of antiviral therapy gain two benefits; protection from HBV and significant increase in rates of SVR. PMID:26147509

  9. Immunization with adenovirus LIGHT-engineered dendritic cells induces potent T cell responses and therapeutic immunity in HBV transgenic mice.

    PubMed

    Jiang, Wenzheng; Chen, Ran; Kong, Xiaobo; Long, Fengying; Shi, Yaru

    2014-07-31

    LIGHT, a TNF superfamily member (TNFSF14), is a type II transmembrane protein expressed on activated T cells and immature dendritic cells (DCs). However, the expression of LIGHT on mature DCs is down-regulated. Recent studies demonstrated that LIGHT provides potent costimulatory activity for T cells, enhancing proliferation and the production of Th1 cytokines independently of the B7-CD28 pathway. Here, we evaluated the effectiveness of peptide-pulsed DC-mediated antiviral immunity in HBV transgenic mice and the immunoadjuvant effect of LIGHT. The bone marrow-derived DCs were modified in vitro with an adenovirus (Ad) vector expressing mouse LIGHT (Ad-LIGHT), the expression of costimulatory molecules was up-regulated and the secretion of cytokines IL-12 and IFN-γ increased. LIGHT-modified DCs enhanced allostimulation for T cells in mixed lymphocyte reaction (MLR). HBV peptide-pulsed DCs elicited HBV specific CD8+ T cell response and reduced the level of HBsAg and HBV DNA in sera of HBV transgenic mice. Importantly, LIGHT-modified DCs could induce stronger antiviral immunity. These results support the concept that genetic modification of DCs with a recombinant LIGHT adenovirus vector may be a useful strategy for antiviral immunotherapy. PMID:24951859

  10. IL-17 and IL-22 genetic polymorphisms in HBV vaccine non- and low-responders among healthcare workers

    PubMed Central

    Borzooy, Zohreh; Streinu-Cercel, Adrian; Mirshafiey, Abbass; Khamseh, Azam; Mahmoudie, Masoud Karkhaneh; Navabi, Shadi Sadat; Nosrati, Marjan; Najafi, Zahra; Hosseini, Mostafa; Jazayeri, Seyed Mohammad

    2016-01-01

    Background Healthcare workers constitute a population at high risk for HBV infection. Efficient vaccination options are available; however, the individual response to HBV vaccination may vary widely between subjects, potentially due to cytokine profiles and genetic variations. In the present study, we investigated the relationship between IL-17 and IL-22 gene polymorphisms versus non- and low-responsiveness to HBV vaccination in healthcare workers. Methods We selected the following IL-17 and IL-22 polymorphisms: rs4711998 (A/G) from IL-17 and rs2227501 (A/T), rs2227503 (A/G), rs1026786 (A/G) from IL-22 sequences genes. These were determined by polymerase chain reaction restriction fragment length polymorphisms. Results The IL-17 rs4711998 GG genotype had a significantly lower frequency in non-responders compared to low-responders (p=0.025). However, we did not identify a relationship between IL-22 rs1026780, rs2227501 and rs2227503 genotypes and the anti-HBs response following HBV vaccination. Conclusion These data suggest that genetic variation in rs4711998 polymorphisms in the IL-17 cytokine may influence vaccine-induced immune responses to HBV vaccine in healthcare workers. PMID:27019828

  11. [Whole-sequence Analyses for 12 HBV C/D Recombinants from a Population in Tibet (China)].

    PubMed

    Liu, Tiezhu; Shen, Liping; Yin, Wenjiao; Wang, Feng; Wang, Fuzhen; Zhang, Guomin; Zheng, Hui; Dunzhu, Duoji; Bi, Shengli; Cui, Fuqiang

    2016-03-01

    We wished to undertake molecular genetic typing and evaluate recombinants of the hepatitis-B virus (HBV) in Tibet (China). Multistage random sampling was used to collect HBsAg-positive samples. Nested polymerase chain reactions were used to amplify the whole sequence of the HBV. DNAstar, MEGA6 and SimPlot were used to assemble sequences, create phylogenetic trees, and undertake recombination analyses. Twelve whole sequences of the HBV of a Tibetan population were collected using these methods. Results showed that all 12 strains were C/D recombinants. Nine of the recombinations were at nt750, and the other three at nt1526. Therefore, the 12 strains could be divided into two types of recombinants: C/Da and C/Db. Analyses of the sequence of the whole genome revealed that the 12 strains belonged to genotype C, and that the nucleotide distance was > 4% between the 12 strains and sub-genotypes C1 to C15 in Genbank. The most likely sub-genotype was C1. Individuals with C/Da were from central and northern Tibet (e.g., Lasa, Linzhi, Ali) and those with C/Db recombinants were from Shannan in southern Tibet. These data suggest that the two types of recombinants had a good distribution in Tibet. Also, they can provide important information for studies on HBV recombination, gene features, virus evolution, as well as the control and prevention of HBV infection in Tibet. PMID:27396158

  12. Two classifiers based on serum peptide pattern for prediction of HBV-induced liver cirrhosis using MALDI-TOF MS.

    PubMed

    Cao, Yuan; He, Kun; Cheng, Ming; Si, Hai-Yan; Zhang, He-Lin; Song, Wei; Li, Ai-Ling; Hu, Cheng-Jin; Wang, Na

    2013-01-01

    Chronic infection with hepatitis B virus (HBV) is associated with the majority of cases of liver cirrhosis (LC) in China. Although liver biopsy is the reference method for evaluation of cirrhosis, it is an invasive procedure with inherent risk. The aim of this study is to discover novel noninvasive specific serum biomarkers for the diagnosis of HBV-induced LC. We performed bead fractionation/MALDI-TOF MS analysis on sera from patients with LC. Thirteen feature peaks which had optimal discriminatory performance were obtained by using support-vector-machine-(SVM-) based strategy. Based on the previous results, five supervised machine learning methods were employed to construct classifiers that discriminated proteomic spectra of patients with HBV-induced LC from those of controls. Here, we describe two novel methods for prediction of HBV-induced LC, termed LC-NB and LC-MLP, respectively. We obtained a sensitivity of 90.9%, a specificity of 94.9%, and overall accuracy of 93.8% on an independent test set. Comparisons with the existing methods showed that LC-NB and LC-MLP held better accuracy. Our study suggests that potential serum biomarkers can be determined for discriminating LC and non-LC cohorts by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. These two classifiers could be used for clinical practice in HBV-induced LC assessment. PMID:23509784

  13. Performance evaluation of 70 hepatitis B virus (HBV) surface antigen (HBsAg) assays from around the world by a geographically diverse panel with an array of HBV genotypes and HBsAg subtypes

    PubMed Central

    Scheiblauer, H; El-Nageh, M; Diaz, S; Nick, S; Zeichhardt, H; Grunert, H-P; Prince, A

    2010-01-01

    Background and Objectives This study was conducted by the International Consortium for Blood Safety (ICBS) to identify high-quality test kits for detection of hepatitis B virus (HBV) surface antigen (HBsAg) for the benefit of developing countries. Materials and Methods The 70 HBsAg test kits from around the world were evaluated comparatively for their clinical sensitivity, analytical sensitivity, sensitivity to HBV genotypes and HBsAg subtypes, and specificity using 394 (146 clinical, 48 analytical and 200 negative) ICBS Master Panel members of diverse geographical origin comprising the major HBV genotypes A-F and the HBsAg subtypes adw2,4, adr and ayw1-4. Results Seventeen HBsAg enzyme immunoassay (EIA) kits had high analytical sensitivity <0·13 IU/ml, showed 100% diagnostic sensitivity, and were even sensitive for the various HBV variants tested. An additional six test kits had high sensitivity (<0·13 IU/ml) but missed HBsAg mutants and/or showed reduced sensitivity to certain HBV genotypes. Twenty HBsAg EIA kits were in the sensitivity range of 0·13–1 IU/ml. The other eight EIAs and the 19 rapid assays had analytical sensitivities of 1 to >4 IU/ml. These assays were falsely negative for 1–4 clinical samples and 17 of these test kits showed genotype dependent sensitivity reduction. Analytical sensitivities for HBsAg of >1 IU/ml significantly reduce the length of the HBsAg positive period which renders them less reliable for detecting HBsAg in asymptomatic HBV infections. Reduced sensitivity for HBsAg with genetic diversity of HBV occurred with genotypes/subtypes D/ayw3, E/ayw4, F/adw4 and by S gene mutants. Specificity of the HBsAg assays was ≥99·5% in 57 test kits and 96·4–99·0% in the remaining test kits. Conclusion Diagnostic efficacy of the evaluated HBsAg test kits differed substantially. Laboratories should therefore be aware of the analytical sensitivity for HBsAg and check for the relevant HBV variants circulating in the relevant population

  14. A Rare HBV Subgenotype D4 with Unique Genomic Signatures Identified in North-Eastern India –An Emerging Clinical Challenge?

    PubMed Central

    Banerjee, Priyanka; Mondal, Rajiv Kumar; Nandi, Madhuparna; Ghosh, Sumantra; Khatun, Mousumi; Chakraborty, Nabendu; Bhattacharya, Swatilekha; RoyChoudhury, Arindam; Banerjee, Soma; Santra, Amal; Sil, Samir; Chowdhury, Abhijit; Bhaumik, Pradip; Datta, Simanti

    2014-01-01

    Background/Aims HBV has been classified into ten genotypes (A–J) and multiple subgenotypes, some of which strongly influence disease outcome and their distribution also correlate with human migration. HBV infection is highly prevalent in India and its diverse population provides an excellent opportunity to study the distinctiveness of HBV, its evolution and disease biology in variegated ethnic groups. The North-East India, having international frontiers on three sides, is one of the most ethnically and linguistically diverse region of the country. Given the paucity of information on molecular epidemiology of HBV in this region, the study aimed to carry out an in-depth genetic characterization of HBV prevailing in North-East state of Tripura. Methods From sera of chronically HBV infected patients biochemical/serological tests, HBV DNA quantification, PCR-amplification, sequencing of PreS/S or full-length HBV genomes were done. HBV genotype/subgenotype determination and sequence variability were assessed by MEGA5-software. The evolutionary divergence times of different HBV subgenotypes were estimated by DNAMLK/PHYLIP program while jpHMM method was used to detect any recombination event in HBV genomes. Results HBV genotypes D (89.5%), C (6.6%) and A (3.9%) were detected among chronic carriers. While all HBV/A and HBV/C isolates belonged to subgenotype-A1 and C1 respectively, five subgenotypes of HBV/D (D1–D5) were identified including the first detection of rare D4. These non-recombinant Indian D4 (IndD4) formed a distinct phylogenetic clade, had 2.7% nucleotide divergence and recent evolutionary radiation than other global D4. Ten unique amino acids and 9 novel nucleotide substitutions were identified as IndD4 signatures. All IndD4 carried T120 and R129 in ORF-S that may cause immune/vaccine/diagnostic escape and N128 in ORF-P, implicated as compensatory Lamivudine resistance mutation. Conclusions IndD4 has potential to undermine vaccination programs or anti

  15. RNA-Seq Based Transcriptome Analysis of Hepatitis E Virus (HEV) and Hepatitis B Virus (HBV) Replicon Transfected Huh-7 Cells

    PubMed Central

    Thakral, Deepshi; Joshi, Prashant; Durgapal, Hemlata; Panda, Subrat Kumar

    2014-01-01

    Pathogenesis of hepatitis B virus (HBV) and hepatitis E virus (HEV) infection is as varied as they appear similar; while HBV causes an acute and/or chronic liver disease and hepatocellular carcinoma, HEV mostly causes an acute self-limiting disease. In both infections, host responses are crucial in disease establishment and/or virus clearance. In the wake of worsening prognosis described during HEV super-infection over chronic HBV hepatitis, we investigated the host responses by studying alterations in gene expression in liver cells (Huh-7 cell line) by transfection with HEV replicon only (HEV-only), HBV replicon only (HBV-only) and both HBV and HEV replicons (HBV+HEV). Virus replication was validated by strand-specific real-time RT-PCR for HEV and HBsAg ELISA of the culture supernatants for HBV. Indirect immunofluorescence for the respective viral proteins confirmed infection. Transcription profiling was carried out by RNA Sequencing (RNA-Seq) analysis of the poly-A enriched RNA from the transfected cells. Averages of 600 million bases within 5.6 million reads were sequenced in each sample and ∼15,800 genes were mapped with at least one or more reads. A total of 461 genes in HBV+HEV, 408 in HBV-only and 306 in HEV-only groups were differentially expressed as compared to mock transfection control by two folds (p<0.05) or more. Majority of the significant genes with altered expression clustered into immune-associated, signal transduction, and metabolic process categories. Differential gene expression of functionally important genes in these categories was also validated by real-time RT-PCR based relative gene-expression analysis. To our knowledge, this is the first report of in vitro replicon transfected RNA-Seq based transcriptome analysis to understand the host responses against HEV and HBV. PMID:24505321

  16. Seroprevalence of HIV, HBV, HCV and syphilis in blood donors in Southern Haryana.

    PubMed

    Arora, Dimple; Arora, Bharti; Khetarpal, Anshul

    2010-01-01

    Blood transfusion is an important mode of transmission of infections to recipients. The aim of the study was to assess the prevalence of transfusion-transmissible infections among blood donors. For this, a 3.5-year retrospective study, from October 2002 to April 2006 was conducted at the blood transfusion centre of Maharaja Agrasen Medical College, Agroha (Hisar) Haryana. Donors were screened for seroprevalence of HIV, HBV, HCV and syphilis. A total of 5849 donors were tested, out of which 4010 (68.6%) were replacement donors and 1839 (31.4%) were voluntary donors. The seroprevalence of HIV was 0.3% in the donors. No voluntary donor was found to be positive for HIV. The low sero-positivity among donors is attributed to pre-donation counseling in donor selection. The seroprevalence of HBV, HCV and syphilis was 1.7%, 1.0% and 0.9% respectively in total donors. The seroprevalence of hepatitis and syphilis was more in replacement donors as compared to voluntary donors. PMID:20551540

  17. A new lignan with anti-HBV activity from the roots of Bombax ceiba.

    PubMed

    Wang, Guo Kai; Lin, Bin Bin; Rao, Rao; Zhu, Kan; Qin, Xiao Ying; Xie, Guo Yong; Qin, Min Jian

    2013-08-01

    A new lignan bombasinol A (1), together with three known compounds was obtained from the ethanol (95%) extract of roots of Bombax ceiba L. through its being subjected to silica gel and Sephadex LH-20 chromatography. Their structures were elucidated as 4-(4-(3,5-dimethoxyphenyl)hexahydrofuro[3,4-c]furan-1-yl)-2-methoxy-phenol (1), 5,6-dihydroxymatairesinol (2), (+)-pinoresinol (3) and matairesinol (4) on the basis of spectroscopic methods, including 1-D and 2-D NMR (HSQC and HMBC) experiments and by comparison of the data with those previously reported literatures. All these compounds were the first reported from Bombacaceae. The anti-Hepatitis B Virus (HBV) activity of all compounds isolated from B. ceiba in the research was evaluated. From the results of the HBV assay, these tested compounds showed inhibitory activity against HepG2 2.2.15 cell lines. Compounds 1-4 showed relative differences in their abilities to inhibit HBsAg secretion, with IC50 values of 118.3, 123.7, 118.9 and 218.2 mM, respectively. PMID:23140388

  18. High occurrence of HBV among STD clinic attenders in Bombay, India.

    PubMed

    Kura, M M; Hira, S; Kohli, M; Dalal, P J; Ramnani, V K; Jagtap, M R

    1998-04-01

    The pattern of sexually transmitted disease (STD) is the basis for designing surveillance of specific STD, their trends and syndromic management protocols. Two hundred and fifteen consecutive first-time STD clinic attenders at a teaching hospital in Bombay were recruited for the study in October 1995. Thorough clinical examination and the following investigations were done: wet mount, Gram stain, Giemsa stain, modified Thayer-Martin (MTM) medium culture, Fontana stain, Venereal Disease Research Laboratory (VDRL), Treponema pallidium haemagglutination test (TPHA), HBsAg and HIV. Ulcerative STD constituted 73.5% of total STD while 15.8% were discharges and 10.2% were genital growths. Ulcers in decreasing order of frequency were chancroid (51.9%), genital herpes (29.1%) and syphilis (14.5). 76.5% of genital discharges were due to gonococcal infection. The high rate of ulcerative STD is possibly an important co-factor for the high HIV prevalence of 31.2% in Bombay. Of 182 patients tested for HBV, 16 (8.8%) were reactive for HBsAg, revealing a high prevalence among STD attenders. A high co-relation of HBsAg positive with either HIV or VDRL requires urgent attention for HBV intervention strategies in this population. PMID:9598752

  19. An upconversion fluorescent resonant energy transfer biosensor for hepatitis B virus (HBV) DNA hybridization detection.

    PubMed

    Zhu, Hao; Lu, Feng; Wu, Xing-Cai; Zhu, Jun-Jie

    2015-11-21

    A novel fluorescent resonant energy transfer (FRET) biosensor was fabricated for the detection of hepatitis B virus (HBV) DNA using poly(ethylenimine) (PEI) modified upconversion nanoparticles (NH2-UCNPs) as energy donor and gold nanoparticles (Au NPs) as acceptor. The PEI modified upconversion nanoparticles were prepared directly with a simple one-pot hydrothermal method, which provides high quality amino-group functionalized UCNPs with uniform morphology and strong upconversion luminescence. Two single-stranded DNA strands, which were partially complementary to each other, were then conjugated with NH2-UCNPs and Au NPs. When DNA conjugated NH2-UCNPs and Au NPs are mixed together, the hybridization between complementary DNA sequences on UCNPs and Au NPs will lead to the quenching of the upconversion luminescence due to the FRET process. Meanwhile, upon the addition of target DNA, Au NPs will leave the surface of the UCNPs and the upconversion luminescence can be restored because of the formation of the more stable double-stranded DNA on the UCNPs. The sensor we fabricated here for target DNA detection shows good sensitivity and high selectivity, which has the potential for clinical applications in the analysis of HBV and other DNA sequences. PMID:26421323

  20. Corner Office: ProQuest's Marty Kahn

    ERIC Educational Resources Information Center

    Fialkoff, Francine; Oder, Norman

    2009-01-01

    In a scant three years at ProQuest, Marty Kahn, CEO, has moved a company coming out of a financial morass back onto solid ground. He came on board after the purchase of ProQuest Information and Learning by the (mostly) privately owned Cambridge Information Group in late 2006 and the merger of ProQuest and CSA to form ProQuest CSA. (It's now just…

  1. BNP and NT-proBNP Test

    MedlinePlus

    ... Peptides Formal name: B-type Natriuretic Peptide; N-terminal pro b-type Natriuretic Peptide Related tests: Cardiac ... for B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) is ...

  2. High Prevalence of HIV, HCV, HBV and Co-Infection and Associated Risk Factors among Injecting Drug Users in Yunnan Province, China

    PubMed Central

    Liu, Feng-Liang; Li, Hong; Jiang, Li; Zhu, Jia-Wu; Zheng, Yong-Tang

    2012-01-01

    Objective To estimate the prevalence of HIV, HCV, HBV and co-infection with 2 or 3 viruses and evaluate risk factors among injecting drug users (IDUs) in Yunnan province, China. Methods 2080 IDUs were recruited from 5 regions of Yunnan Province, China to detect the infection status of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). Statistical analysis was performed to evaluate risk factors related to HIV, HCV and HBV infections. Results The infection rates among all participants were 25.5% for HIV, 77.7% for HCV, 19.2% for HBV, 15% for HIV/HCV, 0.3% for HIV/HBV, 7.8% for HCV/HBV and 7.1% for HIV/HCV/HBV. The prevalence of virus infection varied widely by region in Yunnan of China. Statistical analyses indicated that high prevalence of HIV and HCV among IDUs was positively associated with the duration of drug injection and sharing needles/syringes; besides, HCV infection was associated with the frequency of drug injection. Conclusions HIV, HCV, HBV infections and co-infections were still very prevalent among IDUs in Yunnan province because of drug use behaviors. PMID:22916185

  3. ProMAT: protein microarray analysis tool

    SciTech Connect

    White, Amanda M.; Daly, Don S.; Varnum, Susan M.; Anderson, Kevin K.; Bollinger, Nikki; Zangar, Richard C.

    2006-04-04

    Summary: ProMAT is a software tool for statistically analyzing data from ELISA microarray experiments. The software estimates standard curves, sample protein concentrations and their uncertainties for multiple assays. ProMAT generates a set of comprehensive figures for assessing results and diagnosing process quality. The tool is available for Windows or Mac, and is distributed as open-source Java and R code. Availability: ProMAT is available at http://www.pnl.gov/statistics/ProMAT. ProMAT requires Java version 1.5.0 and R version 1.9.1 (or more recent versions) which are distributed with the tool.

  4. Relationship Between Hepatic Steatosis and the Elevation of Aminotransferases in HBV-Infected Patients With HBe-Antigen Negativity and a Low Viral Load.

    PubMed

    Enomoto, Hirayuki; Aizawa, Nobuhiro; Nishikawa, Hiroki; Ikeda, Naoto; Sakai, Yoshiyuki; Takata, Ryo; Hasegawa, Kunihiro; Nakano, Chikage; Nishimura, Takashi; Yoh, Kazunori; Ishii, Akio; Takashima, Tomoyuki; Iwata, Yoshinori; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-04-01

    Nonalcoholic fatty liver disease has been suggested to be associated with alanine aminotransferase (ALT) elevation in hepatitis B virus (HBV)-infected patients with HBe antigen (HBeAg)-negativity and a low HBV-DNA level. However, few studies have evaluated the association according to histological findings of the liver.Among a total of 198 HBV-infected patients who received a percutaneous liver biopsy, we studied the histological and laboratory findings of HBeAg-negative patients without receiving nucleoside/nucleotide analogues treatment (N = 70) in order to evaluate whether hepatic steatosis and its related metabolic disorders were associated with an elevation in ALT levels in HBeAg-negative patients.In HBeAg-negative patients with a high serum HBV-DNA level (≥2000 IU/mL), the level of HBV-DNA was the only significant factor related to ALT elevation. However, in HBeAg-negative patients with a low HBV-DNA level, the serum ferritin level, and histologically observed hepatic steatosis were significantly associated factors with ALT elevation. When we evaluated 2 metabolic variables (serum ferritin and fasting insulin) that are suggested to be relevant to the presence of progressive disease in Japanese patients, we found that the rate of metabolic disorders was significantly higher among patients with a high ALT level and a low HBV-DNA level than it was among those with other conditions. The triglyceride level and the frequency of moderate or severe hepatic steatosis were significantly higher in patients with a low HBV-DNA level than in those with a high HBV-DNA level.Histologically proven hepatic steatosis and its related metabolic disorders are suggested to be involved in the elevation of aminotransferases of HBeAg-negative patients, particularly those with low HBV-DNA levels. PMID:27124068

  5. Lower than expected hepatitis B virus infection prevalence among first generation Koreans in the U.S.: results of HBV screening in the Southern California Inland Empire

    PubMed Central

    2014-01-01

    Background Hepatitis B virus (HBV) infection is prevalent in Asian immigrants in the USA. California’s Inland Empire region has a population of approximately four million, including an estimated 19,000 first generation Koreans. Our aim was to screen these adult individuals to establish HBV serological diagnoses, educate, and establish linkage to care. Methods A community-based program was conducted in Korean churches from 11/2009 to 2/2010. Subjects were asked to complete a HBV background related questionnaire, provided with HBV education, and tested for serum HBsAg, HBsAb and HBcAb. HBsAg positive subjects were tested for HBV quantitative DNA, HBeAg and HBeAb, counseled and directed to healthcare providers. Subjects unexposed to HBV were invited to attend a HBV vaccination clinic. Results A total of 973 first generation Koreans were screened, aged 52.3y (18-93y), M/F: 384/589. Most (75%) had a higher than high school education and were from Seoul (62.2%). By questionnaire, 24.7% stated they had been vaccinated against HBV. The serological diagnoses were: HBV infected (3.0%), immune due to natural infection (35.7%), susceptible (20.1%), immune due to vaccination (40.3%), and other (0.9%). Men had a higher infection prevalence (4.9% vs. 1.7%, p = 0.004) and a lower vaccination rate (34.6% vs. 44.0%, p = 0.004) compared to women. Self-reports of immunization status were incorrect for 35.1% of subjects. Conclusions This large screening study in first generation Koreans in Southern California demonstrates: 1) a lower than expected HBV prevalence (3%), 2) a continued need for vaccination, and 3) a need for screening despite a reported history of vaccination. PMID:24884673

  6. Relationship Between Hepatic Steatosis and the Elevation of Aminotransferases in HBV-Infected Patients With HBe-Antigen Negativity and a Low Viral Load

    PubMed Central

    Enomoto, Hirayuki; Aizawa, Nobuhiro; Nishikawa, Hiroki; Ikeda, Naoto; Sakai, Yoshiyuki; Takata, Ryo; Hasegawa, Kunihiro; Nakano, Chikage; Nishimura, Takashi; Yoh, Kazunori; Ishii, Akio; Takashima, Tomoyuki; Iwata, Yoshinori; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-01-01

    Abstract Nonalcoholic fatty liver disease has been suggested to be associated with alanine aminotransferase (ALT) elevation in hepatitis B virus (HBV)-infected patients with HBe antigen (HBeAg)-negativity and a low HBV-DNA level. However, few studies have evaluated the association according to histological findings of the liver. Among a total of 198 HBV-infected patients who received a percutaneous liver biopsy, we studied the histological and laboratory findings of HBeAg-negative patients without receiving nucleoside/nucleotide analogues treatment (N = 70) in order to evaluate whether hepatic steatosis and its related metabolic disorders were associated with an elevation in ALT levels in HBeAg-negative patients. In HBeAg-negative patients with a high serum HBV-DNA level (≥2000 IU/mL), the level of HBV-DNA was the only significant factor related to ALT elevation. However, in HBeAg-negative patients with a low HBV-DNA level, the serum ferritin level, and histologically observed hepatic steatosis were significantly associated factors with ALT elevation. When we evaluated 2 metabolic variables (serum ferritin and fasting insulin) that are suggested to be relevant to the presence of progressive disease in Japanese patients, we found that the rate of metabolic disorders was significantly higher among patients with a high ALT level and a low HBV-DNA level than it was among those with other conditions. The triglyceride level and the frequency of moderate or severe hepatic steatosis were significantly higher in patients with a low HBV-DNA level than in those with a high HBV-DNA level. Histologically proven hepatic steatosis and its related metabolic disorders are suggested to be involved in the elevation of aminotransferases of HBeAg-negative patients, particularly those with low HBV-DNA levels. PMID:27124068

  7. [The influence to the function of cellular immunity after being infected by HBV in the PBMC in chronic hepatitis B].

    PubMed

    Xuan, S Y; Sun, Y; Zhang, J

    1997-04-01

    In this study, HBV DNA was detected by PCR from PBMC of chronic hepatitis B. A total number of 54 cases were positive and 71 cases were negative. When detecting the competence of NK cells, the subgroup of T cells the ratio of CD4/CD8, the concentration of sIL-2R in three groups, and between the two CHB groups and a normal control group, the differences between HBV DNA positive group and HBV DNA negative group and between HBVDNA positive group and the normal control group were all dramatically significant (P < 0.01). We also found that a lineal correlation of the competence of NK cells, the ratio of CD4/CD8 and the concentration of sIL-2R(P < 0.01) in the positive group, whereas in the negative group only the ratio of CD4/CD8 was consistent with the concentration of sIL-2R(P < 0.01), and the competence of NK cells did not decrease obviously. The results indicated that it was the infection of HBV in PBMC which caused the disorder of the function of cellular immunity. This finding helped us to explain the pathogenesis of hepatitis B. It could also lay a theoretical ground for the prevention and the treatment of hepatitis B. PMID:9812503

  8. Evaluation of the Procleix Ultrio Plus ID NAT assay for detection of HIV 1, HBV and HCV in blood donors

    PubMed Central

    Makroo, Raj Nath; Chowdhry, Mohit; Bhatia, Aakanksha; Antony, Minimol

    2015-01-01

    Introduction: The Procleix Ultrio Plusassay is a new-generation qualitative in vitro nucleic acid amplification test used to screen for human immunodeficiency virus type 1 (HIV-1) RNA, hepatitis C virus (HCV) RNA and hepatitis B virus (HBV) DNA in blood donors. This study was performed to compare the Procleix Ultrio assay with the new-generation Procleix Ultrio Plus Nucleic Acid Test (NAT) assays. Materials and Methods: Ten thousand three hundred and two donor samples were run in parallel for ID NAT using the Procleix Ultrio and the Procleix Ultrio Plus assay. Simultaneously, enzyme-linked immunosorbent assay testing was performed on an EVOLIS Walk away System for HIV, HCV, HBsAg and anti-HBc. Reactive samples were confirmed using polymerase chain reaction. Results: In the 10,302 samples tested during the study period, we identified 15 NAT yields, and all these revealed HBV DNA in the discriminatory assays. Eight of these were exclusive yields from the Ultrio Plus assay and the remaining seven cases were determined as HBV NAT yield, both by the Procleix Ultrio as well as the Ultrio Plus assays, i.e. “Combined” yields. No HCV or HIV 1 yields were detected during the study period by either of two assays. Conclusion: With an overall yield rate of 1 in 687 and an exclusive yield rate of 1 in 1287, the Procleix Ultrio Plus assay proved to be highly sensitive in detecting occult HBV infections. PMID:25722569

  9. Astershionones A-F, six new anti-HBV shionane-type triterpenes from Aster tataricus.

    PubMed

    Zhou, Wen-Bing; Zeng, Guang-Zhi; Xu, Hui-Min; He, Wen-Jun; Zhang, Yu-Mei; Tan, Ning-Hua

    2014-03-01

    Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1 μM, and cytotoxicity against HepG 2.2.15 cells with a CC50 value of 170.5 μM. 3 also exhibited inhibitory activity against HBV DNA replication with an IC50 value of 22.4 μM. PMID:24393620

  10. CLMA position on HIV/HBV testing of health-care workers. Clinical Laboratory Management Association.

    PubMed

    1992-01-01

    In February 1991, CLMA's National Affairs Committee (NAC) developed a proposed position statement on mandatory HIV/HBV testing of health-care workers. The proposed statement was submitted to the 24-member National Affairs Reactor Panel and, based on their input, appropriate revisions were made. In May 1991, CLMA surveyed the full membership, and, as a result, the following position was adopted. Ninety-six percent of the members responding agreed with principles 1, 2, and 3; 88% agreed with 4, 5, and 6. NAC members include Royal A. Crystal, Chair; Linda D. Bielitzki, J.D., Vice Chair; Michael G. Bissell, M.D., Ph.D.; Earl C. Buck; Michael A. Maffetone, D. A.; Timothy Murray; Laurence J. Peterson; Marianne C. Watters; and Martha A. Feichter, National Affairs Analyst. PMID:10128723

  11. Calibration and Uncertainty in Scenario Simulations with the HBV-N Nitrogen Model

    NASA Astrophysics Data System (ADS)

    Lindstrom, G.; Arheimer, B.

    2002-12-01

    The HBV model, a Swedish precipitation-runoff model has been used extensively in basins all over Sweden for 30 years. Recently, it has been complemented with routines for nitrogen transformation in groundwater, rivers and lakes. The aim is to develop a decision support tool for evaluation of nitrogen load on recipients due to different management practices and policies. The hydrological submodel has a large number of parameters, which are established by calibration, supported by experience from earlier model applications. The root zone leakage of nitrogen, used as input to the HBV model, is simulated by the SOIL-N model, a model for turnover of water, heat and nitrogen in the unsaturated zone. The nitrogen subroutines introduce additional parameters. It is clear that no unique optimum parameter set can be obtained from a single-site model calibation to runoff and nitrogen measurements. This equifinality results in a wide range of uncertainty in the scenario simulations, when studied by ordinary Monte Carlo simulation and acceptance of all parameter sets that produce a fitness criterion above a chosen limit. This is illustrated in a case study for the R”nne † basin in the agricultural region of southern Sweden. The objective of the uncertainty analysis is to explore the uncertainty in the scenario simulations, and to provide support for decision-makers to choose between measures according to expected results and the reliability of these results. However, an ordinary Monte Carlo simulation in which all parameters are simulated and combined randomly does not take advantage of the experience from earlier applications. Therefore, a method is proposed, in which parameter sets are judged not only according to the fitness to observations but also according to their agreement with earlier model applications and hydrological experience, by use of subjective likelihood weights. The range in the scenario simulations obtained from the combined approach is finally compared

  12. Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas.

    PubMed Central

    Edmunds, W. J.; Medley, G. F.; Nokes, D. J.; O'Callaghan, C. J.; Whittle, H. C.; Hall, A. J.

    1996-01-01

    This paper uses meta-analysis of published data and a deterministic mathematical model of hepatitis B virus (HBV) transmission to describe the patterns of HBV infection in high endemicity areas. We describe the association between the prevalence of carriers and a simple measure of the rate of infection, the age at which half the population have been infected (A50), and assess the contribution of horizontal and perinatal transmission to this association. We found that the two main hyper-endemic areas of sub-Saharan Africa and east Asia have similar prevalences of carriers and values of A50, and that there is a negative nonlinear relationship between A50 and the prevalence of carriers in high endemicity areas (Spearman's Rank, P = 0.0086). We quantified the risk of perinatal transmission and the age-dependent of infection to allow a comparison between the main hyper-endemic areas. East Asia was found to have higher prevalences of HBeAg positive mothers and a greater risk of perinatal transmission from HBeAg positive mothers than sub-Saharan Africa, though the differences were not statistically significant. However, the two areas have similar magnitudes and age-dependent rates of horizontal transmission. Results of a simple compartmental model suggest that similar rates of horizontal transmission are sufficient to generate the similar patterns between A50 and the prevalences of carriers. Interrupting horizontal transmission by mass immunization is expected to have a significant, nonlinear impact on the rate of acquisition of new carriers. PMID:8870629

  13. Chemopreventive effect of silymarin on liver pathology in HBV X protein transgenic mice.

    PubMed

    Wu, Yi-Fang; Fu, Shu-Ling; Kao, Cheng-Heng; Yang, Chu-Wen; Lin, Chao-Hsiung; Hsu, Ming-Ta; Tsai, Ting-Fen

    2008-03-15

    There are currently limited therapeutic regimens available for effective treatment of hepatocellular carcinoma (HCC). Silymarin is a naturally derived polyphenolic antioxidant with hepatoprotective properties and is very widely used in clinical application; however, effect of silymarin on spontaneous HCC has not been studied. Silymarin was evaluated for its efficacy against spontaneous carcinogenesis using the HBV X protein (HBx) transgenic model. Silymarin was p.o. given to the HBx transgenic mice from 4 to 6 weeks of age. Our data indicated that silymarin has therapeutic effects on the early stages of liver damage, reversing fatty changes and recovering liver histopathology in a dose-dependent manner. To study the chemopreventive effects on the later stages of carcinogenesis, the mice at 13 months were split into a precancerous group and a group with significant liver carcinogenesis. After silymarin was given to the precancerous mice from 13 to 16 months of age, in contrast to an 80% incidence of HCC development in the untreated transgenic mice, no HCC was detected in any of these mice. Nonetheless, small hyperplastic nodules were detected in 86% of these precancerous mice. In the second group with notable HCC, silymarin was unable to block cancer progression. Although silymarin did not affect HBx expression, intracellular reactive oxygen species levels were decreased, cell proliferation was stimulated, and hepatocyte ultrastructure was found to significantly recover. In conclusion, silymarin exerts beneficial effects on the early stages of liver pathogenesis, preventing and delaying liver carcinogenesis. This drug should be considered as a potential chemopreventive agent for HBV-related hepatocarcinogenesis. PMID:18339886

  14. Genetic variants in IL12 influence both hepatitis B virus clearance and HBV-related hepatocellular carcinoma development in a Chinese male population.

    PubMed

    Tan, Aihua; Gao, Yong; Yao, Ziting; Su, Shining; Jiang, Yonghua; Xie, Yuanliang; Xian, Xiaoying; Mo, Zengnan

    2016-05-01

    IL12 plays a major role not only in inducing appropriate immune responses against viral infections (including HBV) but also in the antitumor immune response. This study was conducted to investigate the relationships of genetic variants in IL12 with hepatitis B virus (HBV) clearance and development of HBV-related hepatocellular carcinoma (HCC). We genotyped three single nucleotide polymorphisms (SNPs) of the IL12A (rs568406 and rs2243115) and IL12B (rs3212227) in 395 HBV-positive HCC patients, 293 persistent HBV carriers and 686 subjects with HBV natural clearance from southern China, using the improved multiplex ligase detection reaction (iMLDR) method. Logistic regression analysis adjusted for age, smoking, and alcohol consumption status showed that rs568408 variant genotypes were significantly associated with host HBV-related HCC risk when compared with persistent HBV carriers, and carriers of the GA + AA genotype decreased the HCC risk in comparison with GG carriers (adjusted OR = 0.53, 95 % CI 0.35-0.80, P = 0.002). No relationships between the rs2243115 and rs3212227 SNPs and HCC risk were observed (all P > 0.05). Besides, rs568408 showed an approaching significant effect on susceptibility to HBV persistent infection (adjusted OR = 1.34, 95 % CI 0.99-1.81, P = 0.057 in dominant genetic models). Furthermore, the TG haplotype was observed to be associated with a significantly increased risk of HBV-related HCC (OR = 1.42, 95 % CI 1.10-1.83, P = 0.006), while TA haplotype was associated with a decreased risk of HBV-related HCC (OR = 0.61, 95 % CI 0.45-0.83, P = 0.002). Our results reveal that the IL12A rs568408 variant may be a marker SNP for risk of both HBV clearance and HBV-related HCC development. PMID:26631030

  15. Association of CMV, HBV, or HCV co-infection with vaccine response in adults with well-controlled HIV infection.

    PubMed

    Troy, S B; Rossheim, A E B; Siik, J; Cunningham, T D; Kerry, J A

    2016-05-01

    Even after CD4 count recovery on antiretroviral therapy, HIV infection is associated with decreased response to most vaccines compared to the general population. Chronic infections with viruses such as cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV), which are more prevalent in HIV-infected populations, have been linked to immune dysfunction and decreased vaccine response in the general population. However, whether co-infection with these other viruses contributes to the decreased vaccine response seen in adults with well-controlled HIV infection is unknown. We conducted a secondary analysis of data and serum from adults with well-controlled HIV infection from an inactivated polio vaccine trial (224 subjects) and a pneumococcal conjugate vaccine study (128 subjects). We evaluated the association of CMV, HBV, or HCV co-infection with post-vaccination antibody levels using both univariate and multivariate analyses, controlling for factors such as age, race, CD4 count, comorbidities, smoking status, and baseline antibody levels. Ninety-three percent, 7%, and 14% of subjects were co-infected with CMV, HBV, and HCV respectively. On both univariate and multivariate analysis, neither CMV nor HCV co-infection were significantly associated with post-vaccination antibody levels to either vaccine. HBV co-infection was significantly associated with post-vaccination antibody concentrations for pneumococcal serotype 7F on univariate analysis and 6A on multivariate analysis, but the association was with higher antibody concentrations. In conclusion, co-infection with CMV, HBV, or HCV does not appear to contribute to the decreased vaccine response seen in adults with well-controlled HIV infection. PMID:26751638

  16. Chronic HBV infection in pregnant immigrants: a multicenter study of the Italian Society of Infectious and Tropical Diseases.

    PubMed

    Sagnelli, Evangelista; Taliani, Gloria; Castelli, Francesco; Bartolozzi, Dario; Cacopardo, Bruno; Armignacco, Orlando; Scotto, Gaetano; Coppola, Nicola; Stroffolini, Tommaso; Sagnelli, Caterina

    2016-04-01

    The aims of the study were to estimate the clinical impact of HBV infection in pregnant immigrants and their family members and to identify a useful approach to managing the healthcare of HBsAg-positive immigrants. Included in this study were 143 HBsAg-positive pregnant immigrants of the 1,970 from countries with intermediate/high HBV endemicity who delivered in 8 Italian hospitals in 2012-2013. In addition, 172 family members of 96 HBsAg-positive pregnant immigrants were tested for serum HBsAg. The median age of the 143 HBsAg-positive pregnant immigrants was 31.0±12.1 years and the length of stay in Italy 5.0±4.1 years; 56.5% were unaware of their HBsAg positivity. HBV DNA was detected in 74.5% of the pregnant immigrants, i.e., 94.3% from Eastern Europe, 72.2% from East Asia and 58.1% from Sub-Saharan Africa. HBV DNA ≥2000 IU/mL was detected in 47.8% of pregnant immigrants, associated with ALT ≥1.5 times the upper normal value in 15% of cases. Anti-HDV was detected in 10% of cases. HBsAg was detected in 31.3% of the 172 family members. All HBsAg-positive immigrants received counseling on HBV infection and its prevention, and underwent a complete clinical evaluation. The findings validate the approach used for the healthcare management of the HBsAg-positive immigrant population. PMID:27196549

  17. A new multiparameter integrated MELD model for prognosis of HBV-related acute-on-chronic liver failure.

    PubMed

    Luo, Yue; Xu, Yun; Li, Mingming; Xie, Ya; Gong, Guozhong

    2016-08-01

    Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is one of the most deadly diseases. Many models have been proposed to evaluate the prognosis of it. However, these models are still controversial. In this study, we aimed to incorporate some characters into model for end-stage liver disease (MELD) to establish a new reliable and feasible model for the prognosis of HBV-ACLF.A total of 530 HBV-ACLF patients who had received antiviral therapy were enrolled into a retrospective study and divided into the training cohort (300) and validation cohort (230). Logistic regression analysis was used to establish a model to predict the 3-month mortality from the patients in the training cohort, and then, the new model was evaluated in the validation cohort.Except for MELD score, 4 other independent factors, namely degree of hepatic encephalopathy (HE), alpha-fetoprotein (AFP), white blood cell (WBC) count, and age, were important for the new model called HBV-ACLF MELD (HAM) model: R = 0.174 × MELD + 1.106 × HE - (0.003 × AFP) + (0.237 × WBC) + (0.103 × Age) - 11.388. The areas under receiver-operating characteristic curve of HAM in the training and validation cohort were 0.894 and 0.868, respectively, which were significantly higher than those of other 7 models. With the best cut-off value of -1.191, HAM achieved higher sensitivity and negative predictive value.We developed a new model that has a great prognostic value of the 3-month mortality of patients with HBV-ACLF. PMID:27559979

  18. PCR-Based Molecular Diagnosis of Hepatitis Virus (HBV and HDV) in HCV Infected Patients and Their Biochemical Study

    PubMed Central

    Anwar, Muhammad Ayaz; Raheel, Ummar; Badshah, Yasmeen; Akhtar, Hashaam; Tamanna, Kosar; Tahir, Muhammad; Sadaf Zaidi, Najam us Sahar

    2016-01-01

    Seroprevalence of HCV indicates that HCV is found in more than 10% of HBV- or HDV-infected patients worldwide leading to liver disease. Here we show HBV and HDV coinfection association with HCV infected Pakistani patients, study of disease severity, and possible interpretation of associated risk factors in coinfected patients. A total of 730 liver diseased patients were included, out of which 501 were found positive for HCV infection via PCR. 5.1% of patients were coinfected with HBV while 1% were coinfected with HBV and HDV both. LFTs were significantly altered in dually and triply infected patients as compared to single HCV infection. Mean bilirubin, AST, and ALT levels were highest (3.25 mg/dL, 174 IU/L, and 348 IU/L) in patients with triple infection while dual infection LFTs (1.6 mg/dL, 61 IU/L, and 74 IU/L) were not high as in single infection (1.9 mg/dL, 76 IU/L, and 91 IU/L). The most prominent risk factor in case of single (22%) and dual infection (27%) group was “reuse of syringes” while in triple infection it was “intravenous drug users” (60%). It is concluded that HBV and HDV coinfections are strongly associated with HCV infected Pakistani patients and in case of severe liver disease the possibility of double and triple coinfection should be kept in consideration. PMID:27366331

  19. Detection and quantitation of HBV DNA in miniaturized samples: multi centre study to evaluate the performance of the COBAS ® AmpliPrep/COBAS ® TaqMan ® hepatitis B virus (HBV) test v2.0 by the use of plasma or serum specimens.

    PubMed

    Berger, Annemarie; Gohl, Peter; Stürmer, Martin; Rabenau, Holger Felix; Nauck, Markus; Doerr, Hans Wilhelm

    2010-11-01

    Laboratory analysis of blood specimens is an increasingly important tool for rapid diagnosis and control of therapy. So, miniaturization of test systems is needed, but reduced specimens might impair test quality. For rapid detection and quantitation of HBV DNA, the COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HBV test has proved a robust instrument in routine diagnostic services. The test system has been modified recently for application of reduced samples of blood plasma and for blood serum, too. The performance of this modified COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HBV v2.0 (HBV v2.0 (this test is currently not available in the USA)) test was evaluated by comparison with the former COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HBV v1.0 (HBV v1.0) test. In this study a platform correlation of both assay versions was done including 275 HBV DNA positive EDTA plasma samples. Comparable results were obtained (R(2)=0.97, mean difference -0.03 log(10)IU/ml). The verification of equivalency of the sample matrix (plasma vs. serum samples tested in HBV v2.0 in the same run) showed comparable results for all 278 samples with a R(2)=0.99 and a mean difference of 0.06 log(10)IU/ml. In conclusion, the new test version HBV v2.0 is highly specific and reproducible and quantifies accurately HBV DNA in EDTA plasma and serum samples from patients with chronic HBV infection. PMID:20728470

  20. Association Between IL-10 Gene Promoter Polymorphisms (-592 A/C, -819 T/C, -1082 A/G) and Susceptibility to HBV Infection in an Iranian Population

    PubMed Central

    Moudi, Bita; Heidari, Zahra; Mahmoudzadeh-Sagheb, Hamidreza; Hashemi, Mohammad; Metanat, Malihe; Khosravi, Soheila; Farrokh, Parisa

    2016-01-01

    Background IL-10 can play a vital role in immune response against HBV. Three biallelic SNPs from the transcription start site control the transcription of the IL-10 gene. An association between susceptibility to HBV and IL-10 polymorphisms has been suggested in patients with HBV infection. Objectives The present study was designed to study the association between polymorphisms in interleukin-10 (-1082 A/G, -819 T/C and -592 A/C) promoter gene and chronic hepatitis B virus (HBV) infection. Patients and Methods 221 chronically infected patients and 200 healthy control subjects were enrolled in the study. Three biallelic (-1082 A/G, -819 T/C and -592 A/C) polymorphisms in the IL-10 promoter gene were determined by PCR-RFLP method. Results Persistent HBV infection was associated with IL-10-1082 AG (P = 0.001) and GG (P = 0.004) genotypes and G (P = 0.000) allele. IL-10-819 T/C and -592 A/C genotype and allele frequencies did not show any correlation with the risk of chronic hepatitis B infection. Conclusions These results suggest that polymorphisms in interleukin-10 gene promoter influence clinical outcome of HBV infection and susceptibility to HBV infection. PMID:27148384

  1. Long-term efficacy of nucleoside monotherapy in preventing HBV infection in HBsAg-negative recipients of anti-HBc-positive donor livers

    PubMed Central

    Chotiyaputta, Watcharasak; Pelletier, Shawn J.; Fontana, Robert J.

    2010-01-01

    Background and aim Transmission of hepatitis B virus (HBV) infection occurs in up to 87.5% of HBsAg-negative recipients of anti-HBc-positive donor livers in the absence of HBV prophylaxis. There is no standardized prophylactic regimen to prevent HBV infection in this setting. The aim of this study was to determine the long-term efficacy of nucleoside analogue to prevent HBV infection in this setting. Methods A retrospective study of HBsAg-negative patients receiving liver transplantation (LT) from anti-HBc-positive donors during a 10-year period. Results Twenty patients were studied, mean age was 50.2 ± 8.3 years, 40% were men, and 90% were Caucasian. The median MELD score at the time of LT was 18 (12–40). None of the patients received hepatitis B immune globulin. Eighteen patients received nucleoside analogue monotherapy: 10 received lamivudine and 8 received entecavir. None of these 18 patients developed HBV infection after a median follow up of 32 (1–75) months. One patient received a second course of hepatitis B vaccine 50 months after LT with anti-HBs titer above 1,000 mIU/mL. Lamivudine was discontinued and the patient remained HBsAg negative 18 months after withdrawal of lamivudine. Two patients who were anti-HBs positive before LT were not started on HBV prophylaxis after LT; both developed HBV infection after LT. Conclusions Nucleoside monotherapy is sufficient in preventing HBV infection in HBsAg-negative recipients of anti-HBc-positive donor livers. HBV prophylaxis is necessary in anti-HBs-positive recipients of anti-HBc-positive donor livers. PMID:21286341

  2. PIN1 genetic polymorphisms and the susceptibility of HBV-related hepatocellular carcinoma in a Guangxi population.

    PubMed

    Huang, Li; Mo, Zhuning; Lao, Xianjun; Zhang, Xiaolian; Liu, Yanqiong; Sui, Jingzhe; Qin, Xue; Li, Shan

    2016-05-01

    Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) plays a critical role in different signaling pathways, cell cycle progression and proliferation, and gene expression, and it has been found to overexpress in many tumor tissues. Recently, researchers have found that PIN1 gene polymorphisms may alter the function of protein and be associated with the risk of cancer. The present study analyzed three common polymorphisms in promoter regions (rs2233678 and rs2233679) and in exon2 (rs2233682) of the PIN1 gene in 254 patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and 235 healthy controls in a Guangxi study population to determine whether any relationship exists between the polymorphisms and the risk of HBV-related HCC. The results revealed that the rs2233679 TT genotype was associated with increased risk of HCC with HBV infection [odds ratio (OR) = 2.04, 95 % confidence interval (95 % CI) = 1.13-3.69, p = 0.019]. This association was stronger in men than in women (OR = 2.17, 95 % CI = 1.09-4.34, p = 0.028) as well as in men 50 years of age and older (OR = 3.91, 95 % CI = 1.29-11.80, p = 0.016); moreover, for alcohol drinkers, being a carrier of the PIN1 rs2233679 CT genotype had a moderately increased risk of HCC (OR = 3.98, 95 % CI = 1.02-15.57, p = 0.047). In contrast, people carrying the rs2233682 GA genotype and A alleles were 0.23 times more likely to develop HCC (OR = 0.23, 95 % CI = 0.06-0.87, p = 0.031 and OR = 0.23, 95 % CI = 0.06-0.87, p = 0.030). No such associations were found in the PIN1 rs2233678 polymorphisms between the HBV-related HCC cases and the controls. In addition, the haplotype GCA was found to be a high protection factor for HCC with HBV infection (OR = 0.14, 95 % CI = 0.03-0.62, p = 0.003). In conclusion, this study's findings suggest that the PIN1 rs2233679 TT genotype, the rs2233682GA genotype, and A alleles

  3. Selection of affinity-improved neutralizing human scFv against HBV PreS1 from CDR3 VH/VL mutant library.

    PubMed

    Chen, YanMin; Bai, Yin; Guo, XiaoChen; Wang, WenFei; Zheng, Qi; Wang, FuXiang; Sun, Dejun; Li, DeShan; Ren, GuiPing; Yin, JieChao

    2016-07-01

    A CDR3 mutant library was constructed from a previously isolated anti-HBV neutralizing Homo sapiens scFv-31 template by random mutant primers PCR. Then the library was displayed on the inner membrane surface in Escherichia coli periplasmic space. Seven scFv clones were isolated from the mutant library through three rounds of screening by flow cytometry. Competition ELISA assay indicates that isolated scFv fragments show more efficient binding ability to HBV PreS1 compared with parental scFv-31. HBV neutralization assay indicated that two clones (scFv-3 and 59) show higher neutralizing activity by blocking the HBV infection to Chang liver cells. Our method provides a new strategy for rapid screening of mutant antibody library for affinity-enhanced scFv clones and the neutralizing scFvs obtained from this study provide a potential alternative of Hepatitis B immune globulin. PMID:27255707

  4. Cost-Effectiveness of HBV and HCV Screening Strategies – A Systematic Review of Existing Modelling Techniques

    PubMed Central

    Geue, Claudia; Wu, Olivia; Xin, Yiqiao; Heggie, Robert; Hutchinson, Sharon; Martin, Natasha K.; Fenwick, Elisabeth; Goldberg, David

    2015-01-01

    Introduction Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers. PMID:26689908

  5. Cell-free circulating mitochondrial DNA content and risk of hepatocellular carcinoma in patients with chronic HBV infection.

    PubMed

    Li, Ling; Hann, Hie-Won; Wan, Shaogui; Hann, Richard S; Wang, Chun; Lai, Yinzhi; Ye, Xishan; Evans, Alison; Myers, Ronald E; Ye, Zhong; Li, Bingshan; Xing, Jinliang; Yang, Hushan

    2016-01-01

    Recent studies have demonstrated a potential link between circulating cell-free mitochondrial DNA (mtDNA) content and cancers. However, there is no study evaluating the association between circulating mtDNA as a non-invasive marker of hepatocellular carcinoma (HCC) risk. We conducted a nested case-control study to determine circulating mtDNA content in serum samples from 116 HBV-related HCC cases and 232 frequency-matched cancer-free HBV controls, and evaluate the retrospective association between mtDNA content and HCC risk using logistic regression and their temporal relationship using a mixed effects model. HCC cases had significantly lower circulating mtDNA content than controls (1.06 versus 2.47, P = 1.7 × 10(-5)). Compared to HBV patients with higher mtDNA content, those with lower mtDNA content had a significantly increased risk of HCC with an odds ratio (OR) of 2.19 (95% confidence interval [CI] 1.28-3.72, P = 0.004). Quartile analyses revealed a significant dose-dependent effect (Ptrend = 0.001) for this association. In a pilot longitudinal sub-cohort of 14 matched cases-control pairs, we observed a trend of dramatically decreased mtDNA content in cases and slightly decreased mtDNA content in controls, with a significant interaction of case-control status with time (Pinteraction = 0.049). Our findings suggest that circulating mtDNA is a potential novel non-invasive biomarker of HCC risk in HBV patients. PMID:27063412

  6. Interleukin-22 Promotes Proliferation of Liver Stem/Progenitor Cells in Mice and Patients with Chronic HBV Infection

    PubMed Central

    Feng, Dechun; Kong, Xiaoni; Weng, Honglei; Park, Ogyi; Wang, Hua; Dooley, Steven; Gershwin, M. Eric; Gao, Bin

    2012-01-01

    Background & Aims Proliferation of liver stem/progenitor cells (LPCs), which can differentiate into hepatocytes or biliary epithelial cells, is often observed in chronically inflamed regions of liver in patients. We investigated how inflammation might promote proliferation of LPCs. Methods We examined the role of interleukin (IL)-22, a survival factor for hepatocytes, on proliferation of LPCs in patients with chronic hepatitis B virus (HBV) infection and in mice. Proliferation of LPCs in mice was induced by feeding a diet that contained 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Results Hepatic expression of IL-22 was increased in patients with HBV and correlated with the grade of inflammation and proliferation of LPCs. Mice on the DDC diet that overexpressed an IL-22 transgene specifically in liver (IL-22TG), or that were infected with an IL-22–expressing adenovirus, had increased proliferation of LPCs. Signal transducer and activator of transcription (STAT) 3, a component of the IL-22 signaling pathway, was activated in LPCs isolated from DDC-fed IL-22TG mice. Deletion of STAT3 from livers of IL-22TG mice reduced proliferation of LPCs. Moreover, the receptors IL-22R1 and IL-10R2 were detected on EpCAM+CD45– LPCs isolated from DDC-fed wild-type mice. Culture of these cells with IL-22 activated STAT3 and led to cell proliferation, but IL-22 had no effect on proliferation of STAT3-deficient EpCAM+CD45– LPCs. IL-22 also activated STAT3 and promoted proliferation of cultured BMOL cells (a mouse LPC line). Conclusion In livers of mice and patients with chronic HBV infection, inflammatory cells produce IL-22, which promotes proliferation of LPCs via STAT3. These findings link inflammation with proliferation of LPCs in patients with HBV infection. PMID:22484119

  7. Development of a Multiplex Real-Time PCR Assay for the Detection of Treponema pallidum, HCV, HIV-1, and HBV.

    PubMed

    Zhou, Li; Gong, Rui; Lu, Xuan; Zhang, Yi; Tang, Jingfeng

    2015-01-01

    Treponema pallidum, hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1, and hepatitis B virus (HBV) are major causes of sexually transmitted diseases passed through blood contact. The development of a sensitive and efficient method for detection is critical for early diagnosis and for large-scale screening of blood specimens in China. This study aims to establish an assay to detect these pathogens in clinical serum specimens. We established a TaqMan-locked nucleic acid (LNA) real-time polymerase chain reaction (PCR) assay for rapid, sensitive, specific, quantitative, and simultaneous detection and identification. The copy numbers of standards of these 4 pathogens were quantified. Standard curves were generated by determining the mean cycle threshold values versus 10-fold serial dilutions of standards over a range of 10(6) to 10(1) copies/μL, with the lowest detection limit of the assay being 10(1) copies/μL. The assay was applied to 328 clinical specimens and compared with enzyme-linked immunosorbent assay (ELISA) and commercial nucleic acid testing (NAT) methods. The assay identified 39 T. pallidum-, 96 HCV-, 13 HIV-1-, 123 HBV-, 5 HBV/HCV-, 1 T. pallidum/HBV-, 1 HIV-1/HCV-, and 1 HIV-1/T. pallidum-positive specimens. The high sensitivity of the assay confers strong potential for its use as a highly reliable, cost-effective, and useful molecular diagnostic tool for large-scale screening of clinical specimens. This assay will assist in the study of the pathogenesis and epidemiology of sexually transmitted blood diseases. PMID:25866106

  8. Prevalence of HBV Infection and Knowledge of Hepatitis B Among Patients Attending Primary Care Clinics in Poland.

    PubMed

    Ganczak, Maria; Dmytrzyk-Daniłów, Gabriela; Korzeń, Marcin; Drozd-Dąbrowska, Marzena; Szych, Zbigniew

    2016-06-01

    It is well known that community awareness of hepatitis B (HB) can lead to vaccination and testing. The study objectives were to assess the prevalence of HBV infection and knowledge of HB among adult patients attending randomly selected primary care clinics. A cross-sectional sero-survey was conducted in March 2013 in the Zgorzelec region, Poland, with the use of an investigator-developed questionnaire containing 22 questions regarding HB knowledge. Serum samples were assayed for anti-HBc total and anti-HBs with enzyme immunoassay. The prevalence of anti-HBc total among 410 participants (median age 56 years) was 10.3 % (95 % CI 7.6-13.8 %), nobody was aware of an infection. The main sources of HB knowledge were the media and medical staff. The mean knowledge score was 14.8 ± 4.9; 76.7 % of the respondents had scores >50 %. Particular gaps were detected relating to knowledge of unprotected sexual intercourse and MTCT; 45.6 % patients were not aware of the potential asymptomatic course of HBV infection, 41.2 % about chronic HB treatment. A patient's low educational level was negatively associated with a high knowledge level; the willingness for further education on HB and HBV vaccination in the past were independently associated with good knowledge. In conclusion, the HBV infection remains a public health threat in Poland, since the prevalence of infection markers in asymptomatic adult patients was high. Knowledge gaps call for awareness campaigns which may increase testing and diagnosis, audiences representing lower education level should be targeted first. Knowledge on HB might serve as an effective tool in decision making regarding vaccination. PMID:26699149

  9. The role of DCs in the immunopathogenesis of chronic HBV infection and the methods of inducing DCs maturation.

    PubMed

    Sun, Hai-Hua; Zhou, Dong-Fang; Zhou, Jun-Ying

    2016-01-01

    Chronic hepatitis B virus (HBV) infection is the result of an inadequate immune response towards the virus. Dendritic cells (DCs), as the most efficient professional antigen-presenting cells (APCs), possess the strongest antigen presenting the effect in the body and can stimulate the initial T cell activation and proliferation. DCs of patients with chronic HBV infection are impaired, resulting in more tolerogenic rather than immunogenic responses, which may contribute to viral persistence. Recently, numerous methods have been developed to induce DCs maturation. To date, recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) combined with interleukin-4 (rhIL-4) has been a classic culture combination to DCs. The recently classified type III interferon group interferon-λ (IFN-λ) displays antiviral, antitumor, and immunoregulatory activity. In our laboratory, we demonstrate that IFN-λ1 combined with rhGM-CSF and rhIL-4 can significantly increase the expression of DC surface molecules and the secretion of interleukin-12 (IL-12) and interferon-γ (IFN-γ) in patients with chronic hepatitis B infection. In this review, we emphasize on the role of DCs in the immunopathogenesis of chronic HBV infection. Importantly, we systematic review that the latest update in the current status of knowledge on the methods of inducing DCs maturation in anti-HBV immunity. What's more, we conclude that IFN-λ1 combined with GM-CSF and IL-4 can induce DCs maturation, which could become a possibility to be applied to the autologus dendritic cell vaccine to treat chronic hepatitis B. PMID:26104380

  10. Cell-free circulating mitochondrial DNA content and risk of hepatocellular carcinoma in patients with chronic HBV infection

    PubMed Central

    Li, Ling; Hann, Hie-Won; Wan, Shaogui; Hann, Richard S.; Wang, Chun; Lai, Yinzhi; Ye, Xishan; Evans, Alison; Myers, Ronald E.; Ye, Zhong; Li, Bingshan; Xing, Jinliang; Yang, Hushan

    2016-01-01

    Recent studies have demonstrated a potential link between circulating cell-free mitochondrial DNA (mtDNA) content and cancers. However, there is no study evaluating the association between circulating mtDNA as a non-invasive marker of hepatocellular carcinoma (HCC) risk. We conducted a nested case-control study to determine circulating mtDNA content in serum samples from 116 HBV-related HCC cases and 232 frequency-matched cancer-free HBV controls, and evaluate the retrospective association between mtDNA content and HCC risk using logistic regression and their temporal relationship using a mixed effects model. HCC cases had significantly lower circulating mtDNA content than controls (1.06 versus 2.47, P = 1.7 × 10−5). Compared to HBV patients with higher mtDNA content, those with lower mtDNA content had a significantly increased risk of HCC with an odds ratio (OR) of 2.19 (95% confidence interval [CI] 1.28–3.72, P = 0.004). Quartile analyses revealed a significant dose-dependent effect (Ptrend = 0.001) for this association. In a pilot longitudinal sub-cohort of 14 matched cases-control pairs, we observed a trend of dramatically decreased mtDNA content in cases and slightly decreased mtDNA content in controls, with a significant interaction of case-control status with time (Pinteraction = 0.049). Our findings suggest that circulating mtDNA is a potential novel non-invasive biomarker of HCC risk in HBV patients. PMID:27063412

  11. Co-incubation with core proteins of HBV and HCV leads to modulation of human dendritic cells.

    PubMed

    Agrawal, Amogh; Samrat, Subodh K; Agrawal, Babita; Tyrrell, D Lorne J; Kumar, Rakesh

    2014-10-01

    Hepatitis B and C (HBV and HCV) are hepatotropic viruses in humans with approximately 350 and 170 million chronic carriers respectively. Since both viruses have similar modes of transmission, many people are co-infected. Co-infection is common in intravenous drug users, HIV-positive individuals, and transplant recipients. Compared to mono-infected patients, co-infected patients exhibit exacerbated liver cirrhosis, hepatocellular carcinoma, and liver failure. Some of the pathogenic effects may be attributed in part to the structural core proteins of both viruses-ones that have displayed immunomodulatory properties. Yet, the effects of their combined interaction on the human immune system remain a mystery. We aimed to elucidate the combined effects of HBV and HCV core proteins on human dendritic cells' (DCs) ability to present antigens and stimulate antigen-specific T-cells. We observed that when DCs, differentiated from human peripheral blood monocytes, were co-incubated with both core proteins, IL-10 production was dramatically enhanced, IL-6, TNF-α, and IL-12 production was significantly reduced, and HLA-DR expression was downregulated. This instant functional and phenotypic modulation of DCs induced by a combination of HBV and HCV core proteins can allow them to behave like tolerizing DCs, inefficiently presenting antigens to CD4+ T-cells and even suppressing induction of the cellular immune response. These results reveal an important mechanism by which HBV and HCV synergistically induce immune tolerance early in infection that may be instrumental in establishing chronic, persistent infections. PMID:25148301

  12. Prevalence of occult HBV among hemodialysis patients in two districts in the northern part of the West Bank, Palestine.

    PubMed

    Dumaidi, Kamal; Al-Jawabreh, Amer

    2014-10-01

    Occult hepatitis B infection is the case with undetectable HBsAg, but positive for HBV DNA in liver tissue and/or serum. Occult hepatitis B infection among hemodialysis patients in Palestine has been understudied. In this study, 148 hemodialysis patients from 2 northern districts in Palestine, Jenin (89) and Tulkarem (59), were investigated for occult hepatitis B, HBV, HCV infections with related risk factors. ELISA and PCR were used for the detection of anti-HBc and viral DNA, respectively. The overall prevalence of occult hepatitis B infection among the study group was 12.5% (16/128). Occult hepatitis B infection is more prevalent among males with most cases (15/16) from Jenin District. About one-third (42/132) of the hemodialysis patients were anti-HBc positive. Approximately 27% of the hemodialysis patients were infected with HCV. Around 20% (28/140) were positive for HBV DNA, but only 8.2% (12/146) of the hemodialysis patients were positive for HBsAg. The comparison between hemodialysis patients with occult hepatitis B infection and those without occult hepatitis B infection for selected risk factors and parameters as liver Enzyme, age, sex, HCV infection, blood transfusion, kidney transplant, anti-HBc, and vaccination showed no statistical significance between both categories. Duration of hemodialysis significantly affected the rate of HCV infection. HCV is significantly higher in hemodialysis patients with both Diabetes mellitus and hypertension. The prevalence of occult hepatitis B infection among hemodialysis patients is high; requiring stringent control policies. HBsAg assay is insufficient test for accurate diagnosis of HBV infection among hemodialysis patients. PMID:24992542

  13. Conformational Plasticity of proNGF

    PubMed Central

    Paoletti, Francesca; Malerba, Francesca; Kelly, Geoff; Noinville, Sylvie; Lamba, Doriano; Cattaneo, Antonino; Pastore, Annalisa

    2011-01-01

    Nerve Growth Factor is an essential protein that supports neuronal survival during development and influences neuronal function throughout adulthood, both in the central and peripheral nervous system. The unprocessed precursor of NGF, proNGF, seems to be endowed with biological functions distinct from those of the mature protein, such as chaperone-like activities and apoptotic and/or neurotrophic properties. We have previously suggested, based on Small Angle X-ray Scattering data, that recombinant murine proNGF has features typical of an intrinsically unfolded protein. Using complementary biophysical techniques, we show here new evidence that clarifies and widens this hypothesis through a detailed comparison of the structural properties of NGF and proNGF. Our data provide direct information about the dynamic properties of the pro-peptide and indicate that proNGF assumes in solution a compact globular conformation. The N-terminal pro-peptide extension influences the chemical environment of the mature protein and protects the protein from proteolytic digestion. Accordingly, we observe that unfolding of proNGF involves a two-steps mechanism. The distinct structural properties of proNGF as compared to NGF agree with and rationalise a different functional role of the precursor. PMID:21818348

  14. Integrated Programs and Pro-Environmental Behaviour

    ERIC Educational Resources Information Center

    Smith, Tiffany

    2008-01-01

    Research suggested that "nature experience as an education method played a role in developing environmental value and attitudes, and was influential in pro-environmental behaviour." Few of these studies however, assessed the long-term influences of outdoor education experiences on participants' pro-environmental behaviour. The Outward Bound Canada…

  15. Impact of current staging systems on treatment strategy for HBV-related hepatocellular carcinoma.

    PubMed

    Yan, Xiaopeng; Qiu, Yudong

    2016-09-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related death worldwide. HCC incidence has increased over the last few years, with more than half of HCC cases being reported in China, where hepatitis B virus (HBV) infection is the main etiologic factor. The heterogeneity in HCC's worldwide distribution and the differences in its etiology in different locations may result in prognosis estimation and therapeutic decision making being more complicated for HCC patients. In the past decade, several clinical staging systems have been developed based on relevant prognostic factors. Among them, the Barcelona Clinic Liver Cancer (BCLC) and Hong Kong Liver Cancer (HKLC) staging systems are the only two classification systems that link prognostic classification to treatment indications. In this review, we mainly focus on the use of the BCLC and HKLC staging systems for guiding therapeutic decision making for HCC, the respective advantages and disadvantages of each classification system, and future perspectives for the improvement of the HKLC model. PMID:26282785

  16. HBV X protein interacts with cytoskeletal signaling proteins through SH3 binding.

    PubMed

    Feng, Huixing; Tan, Tuan Lin; Niu, Dandan; Chen, Wei Ning

    2010-01-01

    The aim of this study was to investigate interactions between cellular SH3-containing proteins and the proline-rich domain in Hepatitis B Virus (HBV) X protein (HBx) The proline-rich domain of HBx (amino acids 19-58) as well as the relevant site-directed mutagenesis (proline to alanine residues) were cloned into pGEX-5X-1 and expressed as GST-PXXP and GST-AXXA probes. Panomics SH3 domain arrays were probed using both GST-PXXP and GST-AXXA to identify potential interacting SH3 domain containing proteins. The specific interactions were confirmed by the immunoprecipitation of the full-length SH3 domain-containing protein. We report here the binding assay which demonstrated interaction between PXXP domain in HBx and the SH3-domain containing proteins, in particular various signaling proteins involved in cytoskeletal reorganization. Our findings were consistent with similar virus-host interactions via SH3 binding for other viruses such as hepatitis C virus (HCV) and human immunodeficiency virus (HIV) Further characterization of the proline-rich binding to SH3 domains could yield important information for the design of novel therapeutic measures against downstream disease causative effects of HBx in the liver cells. PMID:20036864

  17. Estimation of instantaneous peak flow from simulated maximum daily flow using the HBV model

    NASA Astrophysics Data System (ADS)

    Ding, Jie; Haberlandt, Uwe

    2014-05-01

    Instantaneous peak flow (IPF) data are the foundation of the design of hydraulic structures and flood frequency analysis. However, the long discharge records published by hydrological agencies contain usually only average daily flows which are of little value for design in small catchments. In former research, statistical analysis using observed peak and daily flow data was carried out to explore the link between instantaneous peak flow (IPF) and maximum daily flow (MDF) where the multiple regression model is proved to have the best performance. The objective of this study is to further investigate the acceptability of the multiple regression model for post-processing simulated daily flows from hydrological modeling. The model based flood frequency analysis allows to consider change in the condition of the catchments and in climate for design. Here, the HBV model is calibrated on peak flow distributions and flow duration curves using two approaches. In a two -step approach the simulated MDF are corrected with a priory established regressions. In a one-step procedure the regression coefficients are calibrated together with the parameters of the model. For the analysis data from 18 mesoscale catchments in the Aller-Leine river basin in Northern Germany are used. The results show that: (1) the multiple regression model is capable to predict the peak flows with the simulated MDF data; (2) the calibrated hydrological model reproduces well the magnitude and frequency distribution of peak flows; (3) the one-step procedure outperforms the two-step procedure regarding the estimation of peak flows.

  18. Recognition of core-derived epitopes from a novel HBV-targeted immunotherapeutic by T-cells from patients infected by different viral genotypes.

    PubMed

    Godon, Ophelie; Evlachev, Alexei; Bourgine, Maryline; Meritet, Jean-François; Martin, Perrine; Inchauspe, Genevieve; Michel, Marie-Louise

    2015-08-26

    Hepatitis B virus (HBV) infects millions of people worldwide and is a leading cause of liver cirrhosis and hepatocellular carcinoma. Current therapies based on nucleos(t)ide analogs or pegylated-interferon-α lead to control of viral replication in most patients but rarely achieve cure. A potential strategy to control chronic hepatitis B is to restore or induce functional anti-HBV T-cell immune responses using HBV-specific immunotherapeutics. However, viral diversity is a challenge to the development of this class of products as HBV genotypes display a sequence diversity of up to 8%. We have developed a novel HBV-targeted immunotherapeutic, TG1050, based on a non-replicative Adenovirus vector encoding a unique and large fusion protein composed of multiple antigenic regions derived from a HBV genotype D sequence. Using peripheral blood mononuclear cells from 23 patients chronically infected by five distinct genotypes (gt A, B, C, D and E) and various sets of peptides encompassing conserved versus divergent regions of HBV core we have measured ability of TG1050 genotype D core-derived peptides to be recognized by T-cells from patients infected by various genotypes. Overall, PBMCs from 78% of genotype B or C- and 100% genotype A or E-infected patients lead to detection of HBV core-specific T-cells recognizing genotype D antigenic domains located both in conserved and variable regions. This proof-of-concept study supports the clinical development of TG1050 in large patient populations independently of infecting genotypes. PMID:26209840

  19. Seroprevalence of CMV, HSV-2 and HBV among HIV-Infected Malawian Children: A Cross-sectional Survey

    PubMed Central

    Chris Buck, W.; Kazembe, Peter N.; Phiri, Sam; Andrianarimanana, Diavolana; Weigel, Ralf

    2016-01-01

    Background: Little is known about viral co-infections in African human immunodeficiency virus (HIV)-infected children. We examined the prevalence of seromarkers for cytomegalovirus (CMV), herpes simplex virus type 2 (HSV-2) and hepatitis B virus (HBV) infections among HIV-infected, antiretroviral treatment (ART)-naïve children in Lilongwe, Malawi. Methods: Ninety-one serum samples were tested for IgG and IgM antibodies to CMV, and IgG antibodies to HSV-2 and hepatitis B surface antigen (HBsAg). Baseline demographic, clinical and laboratory data were abstracted from electronic records. Results: CMV IgG was the most common positive result in all age groups (in 73% of children <1 year, and 100% in all other groups). Three patients were CMV IgM positive (3.3%), suggesting acute infection. HSV-2 IgG was positive in four patients (4.4%), and HBsAg in two (2.2%). Conclusions: CMV infection occurred early in life, and few children had specific signs of CMV infection at the time of ART initiation. Unrecognized HBV infection represents opportunities for testing and treatment of HIV/HBV co-infected children. PMID:26884443

  20. The recombined cccDNA produced using minicircle technology mimicked HBV genome in structure and function closely.

    PubMed

    Guo, Xiaoyan; Chen, Ping; Hou, Xiaohu; Xu, Wenjuan; Wang, Dan; Wang, Tian-Yan; Zhang, Liping; Zheng, Gang; Gao, Zhi-Liang; He, Cheng-Yi; Zhou, Boping; Chen, Zhi-Ying

    2016-01-01

    HBV covalently closed circular DNA (cccDNA) is drug-resistant and responsible for viral persistence. To facilitate the development of anti-cccDNA drugs, we developed a minicircle DNA vector (MC)-based technology to produce large quantity of recombined cccDNA (rcccDNA) resembling closely to its wild-type counterpart both in structure and function. The rcccDNA differed to the wild-type cccDNA (wtcccDNA) only in that it carried an extra 36-bp DNA recombinant product attR upstream of the preC/C gene. Using a procedure similar to standard plasmid production, milligrams of rcccDNA can be generated in common laboratories conveniently. The rcccDNA demonstrated many essential biological features of wtcccDNA, including: (1) undergoing nucleation upon nucleus entry; (2) serving as template for production of all HBV RNAs and proteins; (3) deriving virions capable of infecting tree shrew, and subsequently producing viral mRNAs, proteins, rcccDNA and infectious virions. As an example to develop anti-cccDNA drugs, we used the Crispr/Cas9 system to provide clear-cut evidence that rcccDNA was cleaved by this DNA editing tool in vitro. In summary, we have developed a convenient technology to produce large quantity of rcccDNA as a surrogate of wtcccDNA for investigating HBV biology and developing treatment to eradicate this most wide-spreading virus. PMID:27174254

  1. Pokemon siRNA Delivery Mediated by RGD-Modified HBV Core Protein Suppressed the Growth of Hepatocellular Carcinoma.

    PubMed

    Kong, Jing; Liu, Xiaoping; Jia, Jianbo; Wu, Jinsheng; Wu, Ning; Chen, Jun; Fang, Fang

    2015-10-01

    Hepatocellular carcinoma (HCC) is a deadly human malignant tumor that is among the most common cancers in the world, especially in Asia. Hepatitis B virus (HBV) infection has been well established as a high risk factor for hepatic malignance. Studies have shown that Pokemon is a master oncogene for HCC growth, suggesting it as an ideal therapeutic target. However, efficient delivery system is still lacking for Pokemon targeting treatment. In this study, we used core proteins of HBV, which is modified with RGD peptides, to construct a biomimetic vector for the delivery of Pokemon siRNAs (namely, RGD-HBc-Pokemon siRNA). Quantitative PCR and Western blot assays revealed that RGD-HBc-Pokemon siRNA possessed the highest efficiency of Pokemon suppression in HCC cells. In vitro experiments further indicated that RGD-HBc-Pokemon-siRNA exerted a higher tumor suppressor activity on HCC cell lines, evidenced by reduced proliferation and attenuated invasiveness, than Pokemon-siRNA or RGD-HBc alone. Finally, animal studies demonstrated that RGD-HBc-Pokemon siRNA suppressed the growth of HCC xenografts in mice by a greater extent than Pokemon-siRNA or RGD-HBc alone. Based on the above results, Pokemon siRNA delivery mediated by RGD-modified HBV core protein was shown to be an effective strategy of HCC gene therapy. PMID:26356810

  2. The recombined cccDNA produced using minicircle technology mimicked HBV genome in structure and function closely

    PubMed Central

    Guo, Xiaoyan; Chen, Ping; Hou, Xiaohu; Xu, Wenjuan; Wang, Dan; Wang, Tian-yan; Zhang, Liping; Zheng, Gang; Gao, Zhi-liang; He, Cheng-Yi; Zhou, Boping; Chen, Zhi-Ying

    2016-01-01

    HBV covalently closed circular DNA (cccDNA) is drug-resistant and responsible for viral persistence. To facilitate the development of anti-cccDNA drugs, we developed a minicircle DNA vector (MC)-based technology to produce large quantity of recombined cccDNA (rcccDNA) resembling closely to its wild-type counterpart both in structure and function. The rcccDNA differed to the wild-type cccDNA (wtcccDNA) only in that it carried an extra 36-bp DNA recombinant product attR upstream of the preC/C gene. Using a procedure similar to standard plasmid production, milligrams of rcccDNA can be generated in common laboratories conveniently. The rcccDNA demonstrated many essential biological features of wtcccDNA, including: (1) undergoing nucleation upon nucleus entry; (2) serving as template for production of all HBV RNAs and proteins; (3) deriving virions capable of infecting tree shrew, and subsequently producing viral mRNAs, proteins, rcccDNA and infectious virions. As an example to develop anti-cccDNA drugs, we used the Crispr/Cas9 system to provide clear-cut evidence that rcccDNA was cleaved by this DNA editing tool in vitro. In summary, we have developed a convenient technology to produce large quantity of rcccDNA as a surrogate of wtcccDNA for investigating HBV biology and developing treatment to eradicate this most wide-spreading virus. PMID:27174254

  3. [Seroconversion and immune response after anti-HBV vaccination in patients on chronic hemodialysis: comparison of two vaccines].

    PubMed

    Polito, Pasquale; Di Lullo, Luca; Iannacci, Giuseppe Roberto; Cecilia, Annalisa; Galderisi, Cristina; Gorini, Antonio

    2011-01-01

    ESRD patients on hemodialysis (HD) have a high risk of HBV infections. Primary prevention through vaccination is a first choice to reduce the morbidity from HBV. Prevention can be accomplished by two types of vaccines. The aim of this study was to evaluate the serological response to HBV vaccination in a population of HD patients who were randomized to Fendrix or Engerix B according to common administration protocols. Ninety-two HD patients were randomized to Fendrix or Engerix B immunization protocols. Patients in the Fendrix arm received four intramuscular administrations of 20 micron g, while patients in the Engerix arm received three intramuscular administrations of 40 micron g with an optional booster dose at two months from the last administration in nonresponders. The seroconversion rates were higher in the Fendrix group than the Engerix group, with faster responses, higher titers and longer duration of immune memory. Fendrix seems to be more effective than the older vaccine, Engerix, especially in patients at high infection risk like those making up our study population. Other crucial factors for good outcomes in patient immunization were biological and dialysis age. This underlines the importance of early immunization protocols such as already discussed by many nephrologists. PMID:22028266

  4. Protective immune barrier against hepatitis B is needed in individuals born before infant HBV vaccination program in China.

    PubMed

    Yang, Shigui; Yu, Chengbo; Chen, Ping; Deng, Min; Cao, Qing; Li, Yiping; Ren, Jingjing; Xu, Kaijin; Yao, Jun; Xie, Tiansheng; Wang, Chencheng; Cui, Yuanxia; Ding, Cheng; Tian, Guo; Wang, Bing; Zhang, Xiaoyan; Ruan, Bing; Li, Lanjuan

    2015-01-01

    The hepatitis B prevalence rate in adults is still at a high to intermediate level in China. Our purpose was to explore the incidence rate and protective immune barrier against hepatitis B in adults in China. A sample of 317961 participants was multi-screened for hepatitis B surface antigens (HBsAg) in a large-scale cohort of the National Hepatitis B Demonstration Project. A total of 5401 persons were newly-infected, representing an incidence rate of 0.81 (95% CI: 0.77-0.85) per 100 person-years after adjusted by gender and age. History of acquired immune deficiency syndrome, birth prior to 1992, coastal residence, family history of HBV, and migrant worker status were significantly associated with higher incidence, while HBV vaccination and greater exercise with lower incidence. The hepatitis B surface antibody (HBsAb) positive rate was negatively correlated with the incidence rate of hepatitis B (r = -0.826). Linear fitting yielded an incidence rate of 1.23 plus 0.02 multiplied by HBsAb positive rate. The study firstly identified the HBsAg incidence rate, which was reduced to 0.1 per 100 person-years after vaccination coverage of about 64%. The protective immune barrier against hepatitis B needs to be established in individuals born prior to the advent of infant HBV vaccination. PMID:26655735

  5. Protective immune barrier against hepatitis B is needed in individuals born before infant HBV vaccination program in China

    PubMed Central

    Yang, Shigui; Yu, Chengbo; Chen, Ping; Deng, Min; Cao, Qing; Li, Yiping; Ren, Jingjing; Xu, Kaijin; Yao, Jun; Xie, Tiansheng; Wang, Chencheng; Cui, Yuanxia; Ding, Cheng; Tian, Guo; Wang, Bing; Zhang, Xiaoyan; Ruan, Bing; Li, Lanjuan

    2015-01-01

    The hepatitis B prevalence rate in adults is still at a high to intermediate level in China. Our purpose was to explore the incidence rate and protective immune barrier against hepatitis B in adults in China. A sample of 317961 participants was multi-screened for hepatitis B surface antigens (HBsAg) in a large-scale cohort of the National Hepatitis B Demonstration Project. A total of 5401 persons were newly-infected, representing an incidence rate of 0.81 (95% CI: 0.77–0.85) per 100 person-years after adjusted by gender and age. History of acquired immune deficiency syndrome, birth prior to 1992, coastal residence, family history of HBV, and migrant worker status were significantly associated with higher incidence, while HBV vaccination and greater exercise with lower incidence. The hepatitis B surface antibody (HBsAb) positive rate was negatively correlated with the incidence rate of hepatitis B (r = −0.826). Linear fitting yielded an incidence rate of 1.23 plus 0.02 multiplied by HBsAb positive rate. The study firstly identified the HBsAg incidence rate, which was reduced to 0.1 per 100 person-years after vaccination coverage of about 64%. The protective immune barrier against hepatitis B needs to be established in individuals born prior to the advent of infant HBV vaccination. PMID:26655735

  6. DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and Rhesus macaques.

    PubMed

    Obeng-Adjei, N; Hutnick, N A; Yan, J; Chu, J S; Myles, D J F; Morrow, M P; Sardesai, N Y; Weiner, D B

    2013-12-01

    There are well over a quarter of a billion chronic hepatitis B virus (HBV) carriers across the globe. Most carriers are at high risk for development of liver cirrhosis and subsequent progression to hepatocellular carcinoma. It is therefore imperative to develop new approaches for immunotherapy against this infection. Antibodies and cytotoxic T cells to different HBV antigens are believed to be important for reducing viral load and clearing HBV-infected cells from the liver. Some of the major challenges facing current vaccine candidates have been their inability to induce both humoral and cellular immunity to multiple antigenic targets and the induction of potent immune responses against the major genotypes of HBV. In this study, highly optimized synthetic DNA plasmids against the HBV consensus core (HBc) and surface (HBs) antigens genotypes A and C were developed and evaluated for their immune potential. These plasmids, which encode the most prevalent genotypes of the virus, were observed to individually induce binding antibodies to HBs antigens and drove robust cell-mediated immunity in animal models. Similar responses to both HBc and HBs antigens were observed when mice and non-human primates were inoculated with the HBc-HBs cocktails. In addition to the cytotoxic T lymphocyte activities exhibited by the immunized mice, the vaccine-induced responses were broadly distributed across multiple antigenic epitopes. These elements are believed to be important to develop an effective therapeutic vaccine. These data support further evaluation of multivalent synthetic plasmids as therapeutic HBV vaccines. PMID:24310062

  7. Intrahepatic Toll-Like Receptor 3 in Chronic HBV Infection Subjects: Asymptomatic Carriers, Active Chronic Hepatitis, Cirrhosis, and Hepatocellular Carcinoma

    PubMed Central

    Yin, Jia Wen; Ping Huang, Mao; Zhong, Bei

    2016-01-01

    Background The entire disease spectrum of chronic HBV infection (CHB) includes asymptomatic carriers (AC), active chronic hepatitis (ACH), cirrhosis (Cir), and hepatocellular carcinoma (HCC). Previous study have demonstrated that the costimulation profiles from the livers of patients influenced immune responses and played various immunological roles in AC, ACH, Cir, and HCC. In addition, activation of TLR3 signaling in the liver may contribute to HBV clearance, although some HBV components are able to block TLR3 signaling and counteract HBV clearance through positive or negative feedback loops. Previous clinical studies have demonstrated that different TLR3 expressions are present in ACH patients, but no studies investigated the expression of TLR3 proteins in the livers of patients with AC, Cir, or HCC. Objectives This study investigated intrahepatic TLR3 expression throughout the entire disease spectrum of CHB patients and assessed the interrelations between TLR3 and costimulation proteins. Patients and Methods Patients with ACH, Cir, HCC, and AC and healthy donors (HD) were recruited. TLR3 expression in the livers of patients were investigated using western blot analysis and immunohistochemistry. Correlations between TLR3 and costimulation proteins, including CD80, CD86, CD83, CD28, CTLA-4, CD40, and ICAM-1, were assessed. Results The TLR3 protein in the ACH group tended toward reduction although the P Value of the comparison between the ACH group and HD group was not statistically significant. The TLR3 levels in the HCC, AC, and Cir groups were higher than those in the HD and ACH groups. TLR3 was not interrelated with all costimulation proteins in the DCs and T cells in all five groups. No group presented any interrelation between TLR3 and CD40, except the AC group. Conclusions The AC, HCC, and Cir patients displayed increased levels of the intrahepatic TLR3 protein compared to the HD and AC patients. Both activation of TLR3/INF-β signaling and inhibition of

  8. Correlates of HIV, HBV, HCV and syphilis infections among prison inmates and officers in Ghana: A national multicenter study

    PubMed Central

    Adjei, Andrew A; Armah, Henry B; Gbagbo, Foster; Ampofo, William K; Boamah, Isaac; Adu-Gyamfi, Clement; Asare, Isaac; Hesse, Ian FA; Mensah, George

    2008-01-01

    Background Prisons are known to be high-risk environments for the spread of bloodborne and sexually transmitted infections. Prison officers are considered to have an intermittent exposure potential to bloodborne infectious diseases on the job, however there has been no studies on the prevalence of these infections in prison officers in Ghana. Methods A national multicenter cross-sectional study was undertaken on correlates of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis infections in sample of prison inmates and officers from eight of ten regional central prisons in Ghana. A total of 1366 inmates and 445 officers were enrolled between May 2004 and December 2005. Subjects completed personal risk-factor questionnaire and provided blood specimens for unlinked anonymous testing for presence of antibodies to HIV, HCV and Treponema pallidum; and surface antigen of HBV (HBsAg). These data were analyzed using both univariate and multivariate techniques. Results Almost 18% (1336) of 7652 eligible inmates and 21% (445) of 2139 eligible officers in eight study prisons took part. Median ages of inmates and officers were 36.5 years (range 16–84) and 38.1 years (range 25–59), respectively. Among inmates, HIV seroprevalence was 5.9%, syphilis seroprevalence was 16.5%, and 25.5% had HBsAg. Among officers tested, HIV seroprevalence was 4.9%, HCV seroprevalence was 18.7%, syphilis seroprevalence was 7.9%, and 11.7% had HBsAg. Independent determinants for HIV, HBV and syphilis infections among inmates were age between 17–46, being unmarried, being illiterate, female gender, being incarcerated for longer than median time served of 36 months, history of homosexuality, history of intravenous drug use, history of sharing syringes and drug paraphernalia, history of participation in paid sexual activity, and history of sexually transmitted diseases. Independent determinants for HIV, HBV, HCV and syphilis infections among officers

  9. Epidemiology, Risk Factors and Genotypes of HBV in HIV-Infected Patients in the Northeast Region of Colombia: High Prevalence of Occult Hepatitis B and F3 Subgenotype Dominance

    PubMed Central

    Bautista-Amorocho, Henry; Castellanos-Domínguez, Yeny Zulay; Rodríguez-Villamizar, Laura Andrea; Velandia-Cruz, Sindi Alejandra; Becerra-Peña, Jeysson Andrey; Farfán-García, Ana Elvira

    2014-01-01

    Introduction Chronic hepatitis B virus (HBV) infection is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. HIV-positive patients are commonly co-infected with HBV due to shared routes of transmission. Objectives Our aim was to determine the risk factors, prevalence, genotypes, and mutations of the Surface S gene of HBV, and occult hepatitis B infection (OBI) among patients infected with HIV in a northeastern Colombian city. Methods A cross-sectional study was conducted with 275 HIV-positive patients attending an outpatient clinic in Bucaramanga, Colombia during 2009–2010. Blood samples were collected and screened for serological markers of HBV (anti-HBs, anti-HBc and HBsAg) through ELISA assay. Regardless of their serological profile, all samples were tested for the HBV S gene by nested-PCR and HBV genotypes were determined by phylogenetic inference. Clinical records were used to examine demographic, clinical, virological, immunological and antiretroviral therapy (ART) variables of HIV infection. Results Participants were on average 37±11 years old and 65.1% male. The prevalence of HIV-HBV coinfection was 12% (95%CI 8.4–16.4) of which 3.3% had active HBV infection and 8.7% OBI. The prevalence of HIV-HBV coinfection was associated with AIDS stage and ART treatment. Sequence analysis identified genotype F, subgenotype F3 in 93.8% of patients and genotype A in 6.2% of patients. A C149R mutation, which may have resulted from failure in HBsAg detection, was found in one patient with OBI. Conclusions The present study found a high prevalence of HIV-HBV coinfection with an incidence of OBI 2.6-fold higher compared to active HBV infection. These findings suggest including HBV DNA testing to detect OBI in addition to screening for HBV serological markers in HIV patients. PMID:25462190

  10. Pro-Anorexia and Pro-Recovery Photo Sharing: A Tale of Two Warring Tribes

    PubMed Central

    Yom-Tov, Elad; Weber, Ingmar; Crain, Steven P

    2012-01-01

    Background There is widespread use of the Internet to promote anorexia as a lifestyle choice. Pro-anorexia content can be harmful for people affected or at risk of having anorexia. That movement is actively engaged in sharing photos on social networks such as Flickr. Objective To study the characteristics of the online communities engaged in disseminating content that encourages eating disorders (known as “pro-anorexia”) and to investigate if the posting of such content is discouraged by the posting of recovery-oriented content. Methods The extraction of pro-anorexia and pro-recovery photographs from the photo sharing site Flickr pertaining to 242,710 photos from 491 users and analyzing four separate social networks therein. Results Pro-anorexia and pro-recovery communities interact to a much higher degree among themselves than what is expected from the distribution of contacts (only 59-72% of contacts but 74-83% of comments are made to members inside the community). Pro-recovery users employ similar words to those used by pro-anorexia users to describe their photographs, possibly in order to ensure that their content appears when pro-anorexia users search for images. Pro-anorexia users who are exposed to comments from the opposite camp are less likely to cease posting pro-anorexia photographs than those who do not receive such comments (46% versus 61%), and if they cease, they do so approximately three months later. Our observations show two highly active communities, where most interaction is within each community. However, the pro-recovery community takes steps to ensure that their content is visible to the pro-anorexia community, both by using textual descriptions of their photographs that are similar to those used by the pro-anorexia group and by commenting to pro-anorexia content. The latter activity is, however, counterproductive, as it entrenches pro-anorexia users in their stance. Conclusions Our results highlight the nature of pro-anorexia and pro

  11. Pro-sociality without empathy.

    PubMed

    Vasconcelos, Marco; Hollis, Karen; Nowbahari, Elise; Kacelnik, Alex

    2012-12-23

    Empathy, the capacity to recognize and share feelings experienced by another individual, is an important trait in humans, but is not the same as pro-sociality, the tendency to behave so as to benefit another individual. Given the importance of understanding empathy's evolutionary emergence, it is unsurprising that many studies attempt to find evidence for it in other species. To address the question of what should constitute evidence for empathy, we offer a critical comparison of two recent studies of rescuing behaviour that report similar phenomena but are interpreted very differently by their authors. In one of the studies, rescue behaviour in rats was interpreted as providing evidence for empathy, whereas in the other, rescue behaviour in ants was interpreted without reference to sharing of emotions. Evidence for empathy requires showing that actor individuals possess a representation of the receiver's emotional state and are driven by the psychological goal of improving its wellbeing. Proving psychological goal-directedness by current standards involves goal-devaluation and causal sensitivity protocols, which, in our view, have not been implemented in available publications. Empathy has profound significance not only for cognitive and behavioural sciences but also for philosophy and ethics and, in our view, remains unproven outside humans. PMID:22859561

  12. Pro-sociality without empathy

    PubMed Central

    Vasconcelos, Marco; Hollis, Karen; Nowbahari, Elise; Kacelnik, Alex

    2012-01-01

    Empathy, the capacity to recognize and share feelings experienced by another individual, is an important trait in humans, but is not the same as pro-sociality, the tendency to behave so as to benefit another individual. Given the importance of understanding empathy's evolutionary emergence, it is unsurprising that many studies attempt to find evidence for it in other species. To address the question of what should constitute evidence for empathy, we offer a critical comparison of two recent studies of rescuing behaviour that report similar phenomena but are interpreted very differently by their authors. In one of the studies, rescue behaviour in rats was interpreted as providing evidence for empathy, whereas in the other, rescue behaviour in ants was interpreted without reference to sharing of emotions. Evidence for empathy requires showing that actor individuals possess a representation of the receiver's emotional state and are driven by the psychological goal of improving its wellbeing. Proving psychological goal-directedness by current standards involves goal-devaluation and causal sensitivity protocols, which, in our view, have not been implemented in available publications. Empathy has profound significance not only for cognitive and behavioural sciences but also for philosophy and ethics and, in our view, remains unproven outside humans. PMID:22859561

  13. Pro-choice: a new militancy.

    PubMed

    Davis, S E

    1989-01-01

    Davis, a pro-choice advocate, describes the reactions of the abortion rights movement to the U.S. Supreme Court's opinion in the 1989 Webster v. Reproductive Health Services case. Viewing the decision that allows individual states to set some restrictions on abortion as a threat to women's reproductive rights, pro-choice advocates have responded "with a new sense of defiance and commitment." Davis describes the demonstrations, sit-ins, and coalitions that give evidence of the new activism of the pro-choice movement. PMID:2606658

  14. Whole-genome DNA methylation and hydroxymethylation profiling for HBV-related hepatocellular carcinoma.

    PubMed

    Ye, Chao; Tao, Ran; Cao, Qingyi; Zhu, Danhua; Wang, Yini; Wang, Jie; Lu, Juan; Chen, Ermei; Li, Lanjuan

    2016-08-01

    Hepatocellular carcinoma (HCC) is a common solid tumor worldwide with a poor prognosis. Accumulating evidence has implicated important regulatory roles of epigenetic modifications in the occurrence and progression of HCC. In the present study, we analyzed 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels in the tumor tissues and paired adjacent peritumor tissues (APTs) from four individual HCC patients using a (hydroxy)methylated DNA immunoprecipitation approach combined with deep sequencing [(h)MeDIP-Seq]. Bioinformatics analysis revealed that the 5-mC levels in the promoter regions of 2796 genes and the 5-hmC levels in 507 genes differed significantly between HCC tissues and APTs. These differential genes were grouped into various clusters and pathways and found to be particularly enriched in the 'metabolic pathways' that include 'Glycolysis/gluconeogenesis', 'Oxidative phosphorylation' and 'Citrate cycle (TCA cycle)', implicating a potential role of metabolic alterations in HCC. Furthermore, 144 genes had both 5-mC and 5-hmC changes in HCC patients, and 10 of them (PCNA, MDM2, STAG1, E2F4, FGF4, FGF19, RHOBTB2, UBE2QL1, DCN and HSP90AA1) were enriched and interconnected in five pathways including the 'Cell cycle', 'Pathway in cancer', 'Ubiquitin mediated proteolysis', 'Melanoma' and 'Prostate cancer' pathways. The genome-wide mapping of 5-mC and 5-hmC in HCC tissues and APTs indicated that both 5-mC and 5-hmC epigenetic modifications play important roles in the regulation of HCC, and there may be some interconnections between them. Taken together, in the present study we conducted the first genome-wide mapping of DNA methylation combined with hydroxymethylation in HBV-related HCC and provided a series of potential novel epigenetic biomarkers for HCC. PMID:27221337

  15. Optical diagnostic of hepatitis B (HBV) and C (HCV) from human blood serum using Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Anwar, Shahzad; Firdous, Shamaraz

    2015-06-01

    Hepatitis is the second most common disease worldwide with half of the cases arising in the developing world. The mortality associated with hepatitis B and C can be reduced if the disease is detected at the early stages of development. The aim of this study was to investigate the potential of Raman spectroscopy as a diagnostic tool to detect biochemical changes accompanying hepatitis progression. Raman spectra were acquired from 20 individuals with six hepatitis B infected patients, six hepatitis C infected patients and eight healthy patients in order to gain an insight into the determination of biochemical changes for early diagnostic. The human blood serum was examined at a 532 nm excitation laser source. Raman characteristic peaks were observed in normal sera at 1006, 1157 and 1513 cm-1, while in the case of hepatitis B and C these peaks were found to be blue shifted with decreased intensity. New Raman peaks appeared in HBV and HCV infected sera at 1194, 1302, 844, 905, 1065 and 1303 cm-1 respectively. A Mat lab subroutine and frequency domain filter program is developed and applied to signal processing of Raman scattering data. The algorithms have been successfully applied to remove the signal noise found in experimental scattering signals. The results show that Raman spectroscopy displays a high sensitivity to biochemical changes in blood sera during disease progression resulting in exceptional prediction accuracy when discriminating between normal and malignant. Raman spectroscopy shows enormous clinical potential as a rapid non-invasive diagnostic tool for hepatitis and other infectious diseases.

  16. Moving horizon estimation for assimilating H-SAF remote sensing data into the HBV hydrological model

    NASA Astrophysics Data System (ADS)

    Montero, Rodolfo Alvarado; Schwanenberg, Dirk; Krahe, Peter; Lisniak, Dmytro; Sensoy, Aynur; Sorman, A. Arda; Akkol, Bulut

    2016-06-01

    Remote sensing information has been extensively developed over the past few years including spatially distributed data for hydrological applications at high resolution. The implementation of these products in operational flow forecasting systems is still an active field of research, wherein data assimilation plays a vital role on the improvement of initial conditions of streamflow forecasts. We present a novel implementation of a variational method based on Moving Horizon Estimation (MHE), in application to the conceptual rainfall-runoff model HBV, to simultaneously assimilate remotely sensed snow covered area (SCA), snow water equivalent (SWE), soil moisture (SM) and in situ measurements of streamflow data using large assimilation windows of up to one year. This innovative application of the MHE approach allows to simultaneously update precipitation, temperature, soil moisture as well as upper and lower zones water storages of the conceptual model, within the assimilation window, without an explicit formulation of error covariance matrixes and it enables a highly flexible formulation of distance metrics for the agreement of simulated and observed variables. The framework is tested in two data-dense sites in Germany and one data-sparse environment in Turkey. Results show a potential improvement of the lead time performance of streamflow forecasts by using perfect time series of state variables generated by the simulation of the conceptual rainfall-runoff model itself. The framework is also tested using new operational data products from the Satellite Application Facility on Support to Operational Hydrology and Water Management (H-SAF) of EUMETSAT. This study is the first application of H-SAF products to hydrological forecasting systems and it verifies their added value. Results from assimilating H-SAF observations lead to a slight reduction of the streamflow forecast skill in all three cases compared to the assimilation of streamflow data only. On the other hand

  17. Manduca sexta proprophenoloxidase activating proteinase-3 (PAP3) stimulates melanization by activating proPAP3, proSPHs, and proPOs

    PubMed Central

    Wang, Yang; Lu, Zhiqiang; Jiang, Haobo

    2014-01-01

    Melanization participates in various insect physiological processes including antimicrobial immune responses. Phenoloxidase (PO), a critical component of the enzyme system catalyzing melanin formation, is produced as an inactive precursor prophenoloxidase (proPO) and becomes active via specific proteolytic cleavage by proPO activating proteinase (PAP). In Manduca sexta, three PAPs can activate proPOs in the presence of two serine proteinase homologs (SPH1 and SPH2). While the hemolymph proteinases (HPs) that generate the active PAPs are known, it is unclear how the proSPHs (especially proSPH1) are activated. In this study, we isolated from plasma of bar-stage M. sexta larvae an Ile-Glu-Ala-Arg-p-nitroanilide hydrolyzing enzyme that cleaved the proSPHs. This proteinase, PAP3, generated active SPH1 and SPH2, which function as cofactors for PAP3 in proPO activation. Cleavage of the purified recombinant proSPHs by PAP3 yielded 38 kDa bands similar in mobility to the SPHs formed in vivo. Surprisingly, PAP3 also can activate proPAP3 to stimulate melanization in a direct positive feedback loop. The enhanced proPO activation concurred with the cleavage activation of proHP6, proHP8, proPAP1, proPAP3, proSPH1, proSPH2, proPOs, but not proHP14 or proHP21. These results indicate that PAP3, like PAP1, is a key factor of the self-reinforcing mechanism in the proPO activation system, which is linked to other immune responses in M. sexta. PMID:24768974

  18. Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68+ Cells during Chronic HBV Infection

    PubMed Central

    Said, Elias A.; Al-Reesi, Iman; Al-Riyami, Marwa; Al-Naamani, Khalid; Al-Sinawi, Shadia; Al-Balushi, Mohammed S.; Koh, Crystal Y.; Al-Busaidi, Juma Z.; Idris, Mohamed A.; Al-Jabri, Ali A.

    2016-01-01

    Background The failure to establish potent anti-HBV T cell responses suggests the absence of an effective innate immune activation. Kupffer cells and liver-infiltrating monocytes/macrophages have an essential role in establishing anti-HBV responses. These cells express the costimulatory molecules CD80 and CD86. CD80 expression on antigen-presenting cells (APCs) induces Th1 cell differentiation, whereas CD86 expression drives the differentiation towards a Th2 profile. The relative expression of CD80, CD86 and PD-L1 on APCs, regulates T cell activation. Few studies investigated CD80 and CD86 expression on KCs and infiltrating monocytes/macrophages in HBV-infected liver and knowledge about the expression of PD-L1 on these cells is controversial. The expression of these molecules together in CD68+ cells has not been explored in HBV-infected livers. Methods Double staining immunohistochemistry was applied to liver biopsies of HBV-infected and control donors to explore CD80, CD86 and PD-L1 expression in the lobular and portal areas. Results Chronic HBV infection was associated with increased CD68+CD86+ cell count and percentage in the lobular areas, and no changes in the count and percentage of CD68+CD80+ and CD68+PD-L1+ cells, compared to the control group. While CD68+CD80+ cell count in portal areas correlated with the fibrosis score, CD68+CD80+ cell percentage in lobular areas correlated with the inflammation grade. Conclusion The upregulation of CD86 but not CD80 and PD-L1 on CD68+ cells in HBV-infected livers, suggests that these cells do not support the induction of potent Th1. Moreover, the expression of CD80 on CD68+ cells correlates with liver inflammation and fibrosis. PMID:27348308

  19. Technology evaluation: PRO-542, Progenics Pharmaceuticals inc.

    PubMed

    Mukhtar, M; Parveen, Z; Pomerantz, R J

    2000-12-01

    Progenics's rCD4-IgG2 (PRO-542) is a recombinant fusion protein, which has been developed using the company's Universal Antiviral Binding (UnAB) technology, and is in phase I/II clinical trials for the treatment of human immunodeficiency virus type I (HIV-1) infection [273391]. At the beginning of 1997, Progenics received a Phase II Small Business Innovation Research Program (SBIR) grant from the National Institute of Allergy and Infectious diseases (NIAID) to fund the development of PRO-542 [236048]. A further grant of $2.7 million was awarded in August 1998 for the clinical evaluation of PRO-542 and other anti-HIV therapies [294200]. Progenics is collaborating with the Aaron Diamond AIDS Research Center (ADARC) in New York and the Center for Disease Control and Prevention in Atlanta [178410]. In February 2000, Progenics and Genzyme Transgenics Corp signed an agreement to continue the development of a transgenic source of PRO-542. Genzyme will develop transgenic goats that produce PRO-542 in their milk in exchange for undisclosed fees and milestone payments. Genzyme will supply PRO-542 to Progenics for clinical trials with a possibility for eventual commercial supply [357291]. Following on from this, in October 2000, Progenics received an SBIR grant to fund a two-year project with Genzyme Transgenics into the development of cost-effective methods for the manufacture of PRO-542, by optimization of the production of the drug in the milk of transgenic dairy animals [385982]. In August 2000, Punk, Ziegel & Company predicted that Progenics Pharmaceuticals will become sustainably profitable in 2003 following the launch of PRO-542 and GMK (Progenics Pharmaceuticals) in 2002 [390063]. PMID:11249748

  20. Hepatocellular Carcinoma Risk of Compensated Cirrhosis Patients with Elevated HBV DNA Levels according to Serum Aminotransferase Levels

    PubMed Central

    Lee, Junggyu; Sinn, Dong Hyun; Kim, Jung Hee; Gwak, Geum-Youn; Kim, Hye Seung; Jung, Sin-Ho; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Yoo, Byung Chul

    2015-01-01

    Sometimes, hepatitis B virus (HBV)-related cirrhotic patients with normal aminotransferase levels are closely followed-up for the elevation of aminotransferase levels instead of prompt antiviral therapy (AVT). We analyzed the long-term hepatocellular carcinoma (HCC) risk according to the aminotransferase levels in a retrospective cohort of 1,468 treatment-naïve, HBV-related, compensated cirrhosis patients with elevated HBV DNA levels (≥2,000 IU/mL). Based on aminotransferase levels, patients were categorized into normal (< 40 U/L, n = 364) and elevated group (≥40 U/L, n = 1,104). During a median of 5.3 yr of follow-up (range: 1.0-8.2 yr), HCC developed in 296 (20%) patients. The 5-yr cumulative HCC incidence rate was higher in patients with elevated aminotransferase level, but was not low in normal aminotransferase level (17% vs. 14%, P = 0.004). During the follow-up, 270/364 (74%) patients with normal aminotransferase levels experienced elevation of aminotransferase levels, and AVT was initiated in 1,258 (86%) patients. Less patients with normal aminotransferase levels received AVT (70% vs. 91%, P < 0.001) and median time to start AVT was longer (17.9 vs. 2.4 months, P < 0.001). AVT duration was an independent factor associated with HCC, and median duration of AVT was shorter (4.0 vs. 2.6 yr, P < 0.001) in patients with normal aminotransferase levels. The HCC risk of compensated cirrhosis patients with normal aminotransferase level is not low, and AVT duration is associated with lowered HCC risk, indicating that prompt AVT should be strongly considered even for those with normal aminotransferase levels. PMID:26539006

  1. Hepatitis B virus genotypes and G1896A precore mutation in 486 Spanish patients with acute and chronic HBV infection.

    PubMed

    Rodriguez-Frias, F; Jardi, R; Buti, M; Schaper, M; Hermosilla, E; Valdes, A; Allende, H; Martell, M; Esteban, R; Guardia, J

    2006-05-01

    This study aims to determine the prevalence of hepatitis B virus (HBV) genotypes (A-F) and their association with the G1896A precore mutation in 486 patients positive for HBV surface antigen. Genotypes were determined by RFLP and precore mutation by real-time PCR. Genotypes D (48.1%) and A (39.5%) were the most common, followed by F (4.1%) and B, C and E (<1%). The A to D ratio (A:D) was 1.4 in HBeAg+ chronic hepatitis B (CHB), 0.6 in HBeAg- CHB and 1.4 in HBeAg- inactive carriers. Distribution of these genotypes was different between HBeAg+ CHB and HBeAg- CHB (P = 0.02), and between HBeAg- CHB and HBeAg- inactive carriers (P = 0.009). Genotype A was the most prevalent in HBeAg+ CHB with elevated alanine aminotransferase (ALT) (68.6%) and genotype D in HBeAg+ CHB with fluctuating ALT (60.7%). There was a difference in genotype prevalence between chronic and acute infection (P = 0.03). The precore mutant correlated with high levels of HBV-DNA in genotype d HBeAg- CHB. Genotype D is not as highly prevalent in Spanish patients as would be expected in a Mediterranean area. The unequal prevalence of genotypes between acute and chronic infection suggests that genotype A is associated with a higher tendency to cause chronic infection. PMID:16637866

  2. Risk of Severe Acute Exacerbation of Chronic HBV Infection Cancer Patients Who Underwent Chemotherapy and Did Not Receive Anti-Viral Prophylaxis

    PubMed Central

    Shih, Chih-An; Chen, Wen-Chi; Yu, Hsien-Chung; Cheng, Jin-Shiung; Lai, Kwok-Hung; Hsu, Jui-Ting; Chen, Hui-Chun; Hsu, Ping-I

    2015-01-01

    Background Reactivation of HBV replication with an increase in serum HBV DNA and alanine aminotransferase (ALT) activity has been reported in 20–50% of hepatitis B carriers undergoing cytotoxic chemotherapy for cancer treatment. Manifestation of HBV reactivation ranges from asymptomatic self-limiting hepatitis to severe progressive hepatic failure and fatal consequences. Aim To investigate the risk of severe acute exacerbation of chronic HBV infection in HBsAg-positive cancer patients with solid tumors or hematological malignancies who underwent chemotherapy without antiviral prophylaxis. Methods A retrospective review of charts was conducted for HBsAg-positive cancer patients in our institution who underwent chemotherapy and did not receive anti-viral prophylaxis between the periods of July 2007 to January 2013. We investigate the incidence of severe acute exacerbation of chronic HBV infection if these patients with a variety of solid tumors and hematological malignancies. Results A total of 156 patients (hematological malignancies: 16; solid tumors: 140) were included. The incidence of severe acute HBV exacerbation in the patients with hematological malignancy was higher than that in solid tumors (25.0% [4/16] vs 4.3% [6/140]); P = 0.005). Additionally, patients receiving rituximab-based chemotherapy had higher acute exacerbation rate than those with non-rituximab-based chemotherapy (40.0% vs 4.1%, P = 0.001). Among the patients with solid tumors, the incidences of severe acute exacerbation of chronic HBV in hepatocellular carcinoma, colorectal cancer, lung cancer, breast cancer, gynecological cancer, urological tract cancer, head/neck cancer and other solid malignancies were 2.3%, 4.0%, 7.1%, 9.0%, 16.7%, 6.7%, 0% and 0%, respectively. Conclusion Severe acute exacerbation of chronic HBV infection may occur in HBsAg-positive patients with a variety of solid tumors who received chemotherapy without adequate anti-viral prophylaxis. Hematological malignancy and

  3. Protein ProQ Influences Osmotic Activation of Compatible Solute Transporter ProP in Escherichia coli K-12

    PubMed Central

    Kunte, H. Jörg; Crane, Rebecca A.; Culham, Doreen E.; Richmond, Deborah; Wood, Janet M.

    1999-01-01

    ProP is an osmoregulatory compatible solute transporter in Escherichia coli K-12. Mutation proQ220::Tn5 decreased the rate constant for and the extent of ProP activation by an osmotic upshift but did not alter proP transcription or the ProP protein level. Allele proQ220::Tn5 was isolated, and the proQ sequence was determined. Locus proQ is upstream from prc (tsp) at 41.2 centisomes on the genetic map. The proQ220::Tn5 and prc phenotypes were different, however. Gene proQ is predicted to encode a 232-amino-acid, basic, hydrophilic protein (molecular mass, 25,876 Da; calculated isoelectric point, 9.66; 32% D, E, R, or K; 54.5% polar amino acids). The insertion of PCR-amplified proQ into vector pBAD24 produced a plasmid containing the wild-type proQ open reading frame, the expression of which yielded a soluble protein with an apparent molecular mass of 30 kDa. Antibodies raised against the overexpressed ProQ protein detected cross-reactive material in proQ+ bacteria but not in proQ220::Tn5 bacteria. ProQ may be a structural element that influences the osmotic activation of ProP at a posttranslational level. PMID:10049386

  4. Whole genome HBV deletion profiles and the accumulation of preS deletion mutant during antiviral treatment

    PubMed Central

    2012-01-01

    Background Hepatitis B virus (HBV), because of its error-prone viral polymerase, has a high mutation rate leading to widespread substitutions, deletions, and insertions in the HBV genome. Deletions may significantly change viral biological features complicating the progression of liver diseases. However, the clinical conditions correlating to the accumulation of deleted mutants remain unclear. In this study, we explored HBV deletion patterns and their association with disease status and antiviral treatment by performing whole genome sequencing on samples from 51 hepatitis B patients and by monitoring changes in deletion variants during treatment. Clone sequencing was used to analyze preS regions in another cohort of 52 patients. Results Among the core, preS, and basic core promoter (BCP) deletion hotspots, we identified preS to have the highest frequency and the most complex deletion pattern using whole genome sequencing. Further clone sequencing analysis on preS identified 70 deletions which were classified into 4 types, the most common being preS2. Also, in contrast to the core and BCP regions, most preS deletions were in-frame. Most deletions interrupted viral surface epitopes, and are possibly involved in evading immuno-surveillance. Among various clinical factors examined, logistic regression showed that antiviral medication affected the accumulation of deletion mutants (OR = 6.81, 95% CI = 1.296 ~ 35.817, P = 0.023). In chronic carriers of the virus, and individuals with chronic hepatitis, the deletion rate was significantly higher in the antiviral treatment group (Fisher exact test, P = 0.007). Particularly, preS2 deletions were associated with the usage of nucleos(t)ide analog therapy (Fisher exact test, P = 0.023). Dynamic increases in preS1 or preS2 deletions were also observed in quasispecies from samples taken from patients before and after three months of ADV therapy. In vitro experiments demonstrated that preS2 deletions alone

  5. Complement Factor 3 Could Be an Independent Risk Factor for Mortality in Patients with HBV Related Acute-on-Chronic Liver Failure

    PubMed Central

    Zhang, Geng-lin; Zhang, Ting; Ye, Yi-nong; Liu, Jing; Zhang, Xiao-hong; Xie, Chan; Peng, Liang; Gao, Zhi-liang

    2016-01-01

    The complement is thought to be involved in the pathogenesis of multiple liver disorders. However, its role in patients with HBV related acute-on-chronic liver failure (HBV-ACLF) remains unclear. Serum levels of the third and fourth complement components (C3, C4) and complement function (CH50) were examined in this prospective, observational study. Associations between their expression and disease activity were analyzed. Survival was analyzed by Kaplan-Meier curves. Predictors of clinical outcome were determined by Cox regression analysis. C3, C4, and CH50 levels were significantly lower in HBV-ACLF patients compared to controls. C3, C4, and CH50 levels were negatively correlated with Tbil levels but positively associated with PTA levels. C3 levels were negatively associated with MELD-Na. C3 levels were significantly lower in HBV-ACLF patients who died compared to patients who survived. In a median hospital stay of 39 days, mortality occurred in 41 patients with a progressive increase based on C3 grade (P = 0.008). The actuarial probability of developing mortality was significantly higher in patients with low C3 grade compared to those with high C3 grade (P < 0.001). Multivariate Cox regression analysis showed that C3 levels were an independent predictor of mortality. Complement played a pathogenic role in HBV-ACLF patients and C3 was an independent predictor of mortality. PMID:27144164

  6. [TLR9 expression is positively correlated with the levels of CD38, HLA-DR and CD95 on peripheral blood mononuclear cells in chronic HBV infected patients].

    PubMed

    Mao, Xuefeng; Peng, Lishan; Liu, Xian; Yang, Yang; Wang, Qihui; Wang, Dengrong; Xiao, Jian; Leng, Jing

    2016-05-01

    Objective To explore the relationship between the expression of TLR9 and the levels of CD38, HLA-DR and CD95 on peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B virus (HBV) infected patients. Methods70 chronic HBV infected patients and 12 healthy donors were enrolled in this study, and density gradient centrifugation was used to isolate PBMCs from peripheral blood with EDTA for anticoagulation. Flow cytometry was used to detect the levels of TLR9, CD38, HLA-DR and CD95 on PBMCs. Results Compared to the healthy donors, chronic HBV infected patients with low viral load or high viral load had significantly higher levels of TLR9, HLA-DR and CD95 on PMBCs. Furthermore, the co-expression rates of TLR9 and CD38, HLA-DR, CD95 on PBMCs were obviously higher than those of the healthy donors. Correlation analysis showed that the expression of TLR9 was positively correlated with CD38 (r=0.345), HLA-DR (r=0.334), CD95 (r=0.227) on PBMCs in the patients with chronic HBV infection. Conclusion The expression of TLR9 increased and was positively associated with CD38, HLA-DR and CD95 on PBMCs during chronic HBV infection. PMID:27126946

  7. Estimation of instantaneous peak flow from daily data using the HBV model

    NASA Astrophysics Data System (ADS)

    Ding, Jie; Haberlandt, Uwe

    2015-04-01

    The length of the observed instantaneous peak flow (IPF) period has a great influence on the flood design whereas these high resolution flow data are not always available. Our previous research has shown that IPFs can be derived from the easier available observed long time series of mean daily flows (MDFs) using a multiple regression model. The primary aim here is to explore the possibility of deriving frequency distributions of IPFs using hydrological modelling with daily and hourly time steps in comparison. In the post-correction approach the rainfall-runoff model is operated on daily time steps , a flood frequency distribution is fitted to the simulated annual MDFs and the resulting daily quantiles are transferred into IPF quantiles using the multiple regression model. In the pre-processing approach, hourly rainfall is produced by disaggregation of daily data. Then the rainfall-runoff model is operated on hourly time steps resulting in a frequency distribution of IPFs. In addition, two calibrations strategies for the hydrological model using the hydrograph and using flow statistics, respectively, are applied for both approaches. Finally, the performances of estimating the IPFs from daily data using these two approaches are compared considering also the two different calibration strategies. The hydrological simulations are carried out with the HBV-IWW model and the case study is carried out for 18 catchments of the Aller-Leine-River basin in northern Germany. The results show that: (1) the multiple regression model is capable to predict IPFs with the simulated MDFs as well; (2) the estimation of extreme flow quantiles in summer is not as good as in winter; (3) both of the two approaches enable a reasonable estimation of IPFs; (4) if on hand the hydrological model is calibrated on the hydrograph the post-correction approach with daily simulations is superior and if on the other hand the model is calibrated on flow statistics the pre-processing with hourly

  8. Evaluating the performance of remotely sensed and reanalysed precipitation data over West Africa using HBV light

    NASA Astrophysics Data System (ADS)

    Jütten, Thomas; Jackisch, Dominik; Diekkrüger, Bernd; Kusche, Jürgen; Eicker, Annette; Springer, Anne

    2016-04-01

    Water is one of the most crucial natural resources in West Africa, where the livelihoods of large parts of the population rely heavily on rain-fed agriculture. Therefore, the modelling of the water balance is an important tool to aid in water resource management. Precipitation is one of most important atmospheric drivers of hydrological models. However, ground-based observation networks are sparse in Western Africa and a further decline in station numbers due to a variety of reasons such as the deterioration of stations or political unrest has been observed in recent years. In ungauged river basins, or basins with insufficiently available precipitation data, several studies have shown that remotely sensed or reanalysed precipitation data may be used to compliment or replace missing information. However, the uncertainties of these datasets over Western Africa are not well examined and a need for further studies is apparent. For validation purposes, precipitation datasets are traditionally compared to in-situ ground measurements. This is not possible in ungauged basins. A new approach to assess the quality of satellite and reanalysis data which is gaining popularity among researchers compares different precipitation datasets using hydrological models. In this so-called hydrological evaluation, ground-truth data is no longer necessary in order to validate a product. The chosen model is calibrated for different precipitation products and the simulated streamflow generated for each product is compared to the measured streamflow. Multiple state of the art satellite and reanalysis precipitation datasets with various spatial resolutions were used in this study, namely: CFSR (0.3125°), CHIRPS (0.05°), CMORPH (0.25°), PERSIANN (0.25°), RFE 2.0 (0.1°), TAMSAT (0.0375°), TRMM 3B42 v7 (0.25°) and TRMM 3B42RT (real time) (0.25°). These datasets were evaluated at the regional as well as local scale using the HBV light conceptual hydrological model for several basins

  9. 31 CFR 50.92 - Determination of pro rata share.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Determination of pro rata share. 50... INSURANCE PROGRAM Cap on Annual Liability § 50.92 Determination of pro rata share. (a) Pro rata loss... compliance with pro rata payments in accordance with the effective date of the PRLP. (2) Determine an...

  10. Human melioidosis reported by ProMED

    PubMed Central

    Nasner-Posso, Katherinn Melissa; Cruz-Calderón, Stefania; Montúfar-Andrade, Franco E.; Dance, David A.B.; Rodriguez-Morales, Alfonso J.

    2015-01-01

    Summary Objective There are limited sources describing the global burden of emerging diseases. A review of human melioidosis reported by ProMED was performed and the reliability of the data retrieved assessed in comparison to published reports. The effectiveness of ProMED was evaluated as a source of epidemiological data by focusing on melioidosis. Methods Using the keyword ‘melioidosis’ in the ProMED search engine, all of the information from the reports and collected data was reviewed using a structured form, including the year, country, gender, occupation, number of infected individuals, and number of fatal cases. Results One hundred and twenty-four entries reported between January 1995 and October 2014 were identified. A total of 4630 cases were reported, with death reported in 505 cases, suggesting a misleadingly low overall case fatality rate (CFR) of 11%. Of 20 cases for which the gender was reported, 12 (60%) were male. Most of the cases were reported from Australia, Thailand, Singapore, Vietnam, and Malaysia, with sporadic reports from other countries. Conclusions Internet-based reporting systems such as ProMED are useful to gather information and synthesize knowledge on emerging infections. Although certain areas need to be improved, ProMED provided good information about melioidosis. PMID:25975651

  11. [Prevalence change of HGV(GBV-C) infection and its coinfection with HBV a HCV infections in haemodialysis patients].

    PubMed

    Klusonová, Hana; Stepánová, Vlasta; Plísková, Lenka; Stilec, Roman

    2003-01-01

    Prevalence of HGV(GBV-C) infection and its coinfection with HBV a HCV infections were studied in group of 82 haemodialysis patients. This study was realized 20 months latter again -- 16 patients from 82 were running in dialysis, 17 patients were transplanted and 49 patients died (non of this viruses was cause of their death). HGV(GBV-C) RNA was detected in serum of 22 patients, 20 months latter it was detected in serum of 3 patients; one positive was new. 20 months latter any HGV(GBV-C) RNA was not detected in serum of 4 originally positive patients. Three of ten HBsAg positive patients were coinfected by HGV(GBV-C) RNA; 20 months latter any coinfection was found. In the first we found HGV(GBV-C) RNA in serum of 5 anti-HCV positive patients and in serum of 1 HCV RNA positive patient; 20 months latter it was in serum of 1 and 1 respectively. Elevation of ALT and AST levels were found in serum of 3 from 82 patients; two patients were coinfected with HBV or HCV. Any from 2 running dialysis patients with elevation of ALT and AST levels was not HGV(GBV-C) RNA positive. This virus is not probably frequent cause of liver disease in dialysis patients and it is not necessary to routinely screen for HGV(GBV-C) infection in this group of patients. PMID:19569590

  12. CDC42-Interacting Protein 4 Gene Is Down Trans-Regulated by HBV DNA polymerase Trans Activated Protein 1

    PubMed Central

    LUN, Yongzhi; XU, Chongbo; CHI, Qing; WANG, Xuelei; SUI, Wen; JIANG, Sujuan

    2014-01-01

    Abstract Background Hepatitis B Virus (HBV) DNA polymerase transactivated protein 1 (HBVDNAPTP1) is a novel protein transactivated by HBV DNA polymerase, screened by suppression subtractive hybridization technique (GenBank accession no: AY450389). The biological function of HBVDNAPTP1 was investigated in this study. Methods We constructed a vector pcDNA3.1 (-)/myc-His A-HBVDNAPTP1 and used it to transfect acute monocytic leukemia cell line THP-1. HBVDNAPTP1 expression was detected by western blot analysis in the cells. A cDNA library of genes transactivated by HBVDNAPTP1 in THP-1 cells was made in pGEM-T Easy using suppression subtractive hybridization (SSH). The cDNAs were sequenced and analyzed with BLAST search against the sequences in GenBank. Results Some sequences, such as CIP4, might be involved in apoptosis development. mRNA and protein expression of CIP4 was identified by Real time RT-PCR and western blot in THP-1 cells. HBVDNAPTP1 could down-regulate the expression of CIP4 at both transcription and translation levels. Conclusion HBVDNAPTP1 may be involved in the positive regulation on the initiation of monocyte apoptosis. The result contribute to reveal the HBVDNAPTP1 biological functions and provide new evidences for further exploration of the regulatory mechanism of HBVDNAPTP1. PMID:25988087

  13. Immunological persistence in 5 y olds previously vaccinated with hexavalent DTPa-HBV-IPV/Hib at 3, 5, and 11 months of age.

    PubMed

    Silfverdal, Sven A; Assudani, Deepak; Kuriyakose, Sherine; Van Der Meeren, Olivier

    2014-01-01

    The combined diphtheria-tetanus-acellular pertussis-hepatitis B-poliomyelitis/Haemophilus influenza vaccine (DTPa-HBV-IPV/Hib: Infanrix™ hexa, GlaxoSmithKline Vaccines) is used for primary vaccination of infants in a range of schedules world-wide. Antibody persistence after 4 DTPa-HBV-IPV/Hib doses in the first 2 y of life has been documented, but long-term persistence data following the 3, 5, 11-12 months (3-5-11) infant vaccination schedule, employed for example in Nordic countries, are limited. We assessed antibody persistence in 57 5-year-old children who had received either DTPa-HBV-IPV/Hib or DTPa-IPV/Hib (Infanrix™-IPV/Hib, GlaxoSmithKline Vaccines) in the 3-5-11 schedule. Among DTPa-HBV-IPV/Hib recipients, 7/12 retained seroprotective antibody concentrations for diphtheria, 10/12 for tetanus, 5/12 for hepatitis and 10/12 for Hib. Detectable antibodies were observed for 0/12 children for pertussis toxin (PT), 12/12 for filamentous haemagglutinin (FHA) and 8/12 for pertactin (PRN). Among DTPa-IPV/Hib recipients, 28/45 retained seroprotective anti-diphtheria concentrations, 34/44 for tetanus and 40/45 for Hib. Detectable antibodies were observed for 9/45 children for PT, 41/45 for FHA and 34/45 for PRN. Antibody persistence in DTPa-HBV-IPV/Hib and DTPa-IPV/Hib-vaccinees appeared similar in 5 y olds to that previously observed in children of a similar age who had received 4 prior doses of DTPa-HBV-IPV/Hib (or DTPa-IPV/Hib). As in subjects primed with 4 prior doses, we observed that antibodies markedly declined by 5 y of age, calling for the administration of a pre-school booster dose in order to ensure continued protection against pertussis. PMID:25483640

  14. Analysis of Risk Factors Associated with the Development of Hepatocellular Carcinoma in Chronic HBV-Infected Chinese: A Meta-Analysis.

    PubMed

    Lyu, Xiang; Liu, Kui; Chen, Yongdi; Wang, Zhifang; Yao, Jun; Cai, Gaofeng; Jiang, Zhenggang; Wang, Zhengting; Jiang, Jianmin; Gu, Hua

    2016-01-01

    Hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC) in China. At present, there still are 9.3 million chronic HBV-infected Chinese. Numerous studies have explored the association between possible factors and hepatocellular carcinoma risk, however, the results remains inconsistent. Therefore, we did this pooled analysis so as to get a precise result. Here, we took the chronic HBV-infected Chinese as the object. We systematically searched for studies evaluating whether the proposed factors changed HCC risk in PubMed, Chinese National Knowledge Infrastructure, VIP database and Wanfang data. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by Review Manager 5.0 and publication bias was determined by Begg's test and Egger's test. In total, 3165 cases and 10,896 controls from 27 studies were included in this meta-analysis. Our results showed that pooled OR with 95% CI for each of the factors investigated were: non-antiviral treatment 2.70 (2.01, 3.62), high HBV DNA levels 2.61 (1.73, 3.94), alcohol consumption 2.19 (1.53, 3.13), a family history of HCC 3.58 (2.53, 5.06) and male gender 2.14 (1.68, 2.73), respectively. Our meta-analysis supports that high HBV DNA levels, non-antiviral treatment, alcohol consumption, a family history of HCC and male gender contributed to the risk of hepatocellular carcinoma in chronic HBV-infected Chinese from currently available evidence. Given the high prevalence of the non-antiviral treatment and alcohol drinking, behavior interventions for the two factors should be tackled first. PMID:27322300

  15. Analysis of Risk Factors Associated with the Development of Hepatocellular Carcinoma in Chronic HBV-Infected Chinese: A Meta-Analysis

    PubMed Central

    Lyu, Xiang; Liu, Kui; Chen, Yongdi; Wang, Zhifang; Yao, Jun; Cai, Gaofeng; Jiang, Zhenggang; Wang, Zhengting; Jiang, Jianmin; Gu, Hua

    2016-01-01

    Hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC) in China. At present, there still are 9.3 million chronic HBV-infected Chinese. Numerous studies have explored the association between possible factors and hepatocellular carcinoma risk, however, the results remains inconsistent. Therefore, we did this pooled analysis so as to get a precise result. Here, we took the chronic HBV-infected Chinese as the object. We systematically searched for studies evaluating whether the proposed factors changed HCC risk in PubMed, Chinese National Knowledge Infrastructure, VIP database and Wanfang data. Odds ratios (OR) with 95% confidence intervals (CI) were calculated by Review Manager 5.0 and publication bias was determined by Begg’s test and Egger’s test. In total, 3165 cases and 10,896 controls from 27 studies were included in this meta-analysis. Our results showed that pooled OR with 95% CI for each of the factors investigated were: non-antiviral treatment 2.70 (2.01, 3.62), high HBV DNA levels 2.61 (1.73, 3.94), alcohol consumption 2.19 (1.53, 3.13), a family history of HCC 3.58 (2.53, 5.06) and male gender 2.14 (1.68, 2.73), respectively. Our meta-analysis supports that high HBV DNA levels, non-antiviral treatment, alcohol consumption, a family history of HCC and male gender contributed to the risk of hepatocellular carcinoma in chronic HBV-infected Chinese from currently available evidence. Given the high prevalence of the non-antiviral treatment and alcohol drinking, behavior interventions for the two factors should be tackled first. PMID:27322300

  16. Across-sectional study on anxiety and stress in pregnant women with chronic HBV infection in the People’s Republic of China

    PubMed Central

    Zhou, Fen; Li, Jianju; Lin, Keke; Ji, Ping; Sun, Yumei

    2015-01-01

    Purpose To investigate the anxiety and pregnancy-associated stress of pregnant women with chronic hepatitis B virus (HBV) infection in the People’s Republic of China and analyze the relationship between anxiety and pregnancy-associated stress in the hope of finding ways to reduce the stress or improve the coping skills for these mothers-to-be during pregnancy. Methods A cross-sectional study was conducted. One hundred and sixty chronic HBV-infected pregnant women (HBV group) and 160 healthy pregnant women (control group) selected from three Peking University-affiliated hospitals participated in the study, and completed the State-Trait Anxiety Inventory (STAI) and Pregnancy Stress Rating Scale (PSRS) survey. Results The mean scores of STAI and PSRS for the HBV group were higher than for the control group. Factor 2 of PSRS (stress caused by worrying about mother and child’s health and safety) was the highest, and was significantly higher in the HBV group than in the control group. Correlation analysis showed STAI scores were significantly correlated with economic status and diagnosis, as well as the total score, factor 1 (stress about identifying with the role of mother), and factor 2 of PSRS, but not significantly correlated with factor 3 of PSRS (stress caused by the changes of body shape and physical activity). Conclusion Pregnant women with chronic HBV infection experienced higher levels of anxiety and stress than healthy pregnant women. Their major stress came from concerns for the health and safety of the mother and the child. PMID:26346004

  17. Epidemiology of HBV S-gene mutants in the Liguria Region, Italy: Implications for surveillance and detection of new escape variants.

    PubMed

    Sticchi, Laura; Caligiuri, Patrizia; Cacciani, Roberto; Alicino, Cristiano; Bruzzone, Bianca

    2013-03-01

    HBV surface antigen (HBsAg) variants may impair diagnosis or allow the virus to escape vaccine-induced immunity and their circulation in the population can represent a Public Health threat. Their prevalence, however, is not yet completely established. Evidence indicates that amino acid substitutions within HBsAg can lead to conformational changes which allow mutated HBV to escape the vaccine-induced antibodies used in the screening tests. In such scenario, the aim of this study was to investigate the prevalence of HBV S-Gene escape mutants by sequencing the gene in a cohort of Ligurian patients monitored for viral load, genotype and drug resistance and to evaluate the risk of false negative HBsAg detection by routine screening tests. From 2007 to 2011, in 256 consecutive samples from Ligurian HBV positive patients sequencing assay for detection of RT/S-Gene mutations using Trugene HBV Genotyping kit (Siemens Healthcare Diagnostics Inc., Tarrytown, NY) was performed. Serological HBV tests and viral load were also performed. Analyzed sequences revealed G145R mutation in 8/256 (3.1%) examined sequences, it was alone in 5 patients and accompanied by other HBsAg mutations in 3 samples. HBsAg resulted undetectable by 3 of the 8 samples, derived from patients with multiple mutations: T126I-T131A-C139Y-E/D144G, T126I-M133L, and P120Q-T126I. The emergence of these mutants, at least the G145R, has already been addressed as a public health concern because of its capability of escaping the immune system. In the present study we point out a second aspect connected with their existence and with similar potential negative impact on public health, that is their capability of escape punctual detection. PMID:23296324

  18. Naturally occurring basal core promoter A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma: a meta-analysis

    PubMed Central

    Lu, Yunfei; Xu, Qingnian; Tang, Bozong; Chen, Xiaorong

    2016-01-01

    Basal core promoter (BCP) A1762T/G1764A dual mutations in hepatocarcinogenesis remain controversial. Published studies up to June 1, 2015 investigating the frequency of A1762T/G1764A dual mutations from chronic hepatitis B virus (HBV) infection, including hepatocellular carcinoma (HCC), were systematically identified. A total of 10,240 patients with chronic HBV infection, including 3729 HCC cases, were included in 52 identified studies. HCC patients had a higher frequency of BCP A1762T/G1764A dual mutations compared with asymptomatic HBsAg carriers (ASC) and patients with chronic hepatitis B (CHB) and liver cirrhosis (LC) (OR = 5.59, P < 0.00001; OR = 2.87, P < 0.00001; OR = 1.55, P = 0.02, respectively). No statistically significant difference was observed in the frequency of A1762T/G1764A dual mutations in cirrhotic HCC versus non-cirrhotic HCC patients (OR = 2.06, P = 0.05). Chronic HBV-infected patients and HCC patients with genotype B had a significantly lower risk of A1762T/G1764A dual mutations compared with patients with genotype C (OR = 0.30, P < 0.0001 and OR = 0.34, P = 0.04, respectively). In HBV genotype C subjects, A1762T/G1764A dual mutations contributed to significantly higher risk for HCC developing compared with non-mutation ones (OR = 3.47, P < 0.00001). In conclusion, A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma, particularly in an HBV genotype C population, even without progression to cirrhosis. PMID:26848866

  19. The Importance of Lamivudine Therapy in Liver Cirrhosis Patients Related HBV with Advanced Hepatocellular Carcinoma Receiving Hepatic Arterial Infusion Chemotherapy

    PubMed Central

    Momiyama, Koichi; Nagai, Hidenari; Ogino, Yu; Mukouzu, Takanori; Matsui, Daigo; Kogame, Michio; Matsui, Teppei; Wakui, Noritaka; Shinohara, Mie; Igarashi, Yoshinori; Sumino, Yasukiyo

    2015-01-01

    Purpose: We have previously reported that continuous hepatic arterial infusion chemotherapy (HAIC) might be more effective for advanced hepatocellular carcinoma (aHCC) in patients with liver cirrhosis (LC) related to HCV infection (C-LC) or alcohol abuse (A-LC) than in patients who had LC related to HBV infection (B-LC). The aim of the present study was to retrospectively assess the efficacy of lamivudine therapy for B-LC patients with aHCC undergoing HAIC. Methods: Seventeen adult Japanese B-LC patients with aHCC were treated by HAIC with or without lamivudine (100 mg/day) between 2002 and 2008 at our hospital. Their tumors were inoperable according to computed tomography findings. HAIC (LV at 12 mg/hr, CDDP at 10 mg/hr, and 5-FU at 250 mg/22 hr) was given via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneously implanted drug delivery system. Results: Nine of the 17 patients received lamivudine at a dose of 100 mg/day together with HAIC (LAM group), while 8 patients did not receive lamivudine and only had HAIC (non-LAM group). The response rate was 12.5 in the non-LAM group and 0.0% in the LAM group. However, the survival of the LAM group was better than that of the non-LAM group, although there was no significant difference between them. The median survival time of the LAM and non-LAM groups was 310 and 157 days, respectively. HBV-DNA levels were significantly lower after chemotherapy compared with that before chemotherapy in the LAM group. In the non-LAM group, the percentage of Th2 cells before HAIC and after HAIC was significantly higher than in the control group. However, the percentage of Th2 cells in the LAM group after HAIC was not different from that in the control group, although it was significantly higher in the LAM group than in the control group before chemotherapy. Conclusions: These results indicate that lamivudine therapy may prolong the survival of B-LC patients receiving HAIC for aHCC by reducing HBV

  20. Pocahontas: Problematizing the Pro-Social.

    ERIC Educational Resources Information Center

    Aidman, Amy; Reese, Debbie

    The Disney film "Pocahontas" appears to be an attempt to respond to growing cultural diversity, calls for multiculturalism, and strong female role models in the United States. This paper provides an analysis of the film, examining how Disney's claims to the creation of positive, pro-social representations of women and Native Americans in…

  1. Ubiquitin-hepatitis B core antigen-cytoplasmic transduction peptide enhances HBV-specific humoral and CTL immune responses in vivo.

    PubMed

    Song, Linlin; Zhuo, Meng; Tang, Yuyan; Chen, Xiaohua; Tang, Zhenghao; Zang, Guoqing

    2014-11-01

    Therapeutic strategies based on an enhanced hepatitis B virus (HBV)-specific cytotoxic T lymphocyte (CTL) activity may eradicate HBV. We previously verified that a fusion protein ubiquitin (Ub)-hepatitis B core antigen (HBcAg)-cytoplasmic transduction peptide (CTP) can enter the cytoplasm of dendritic cells and enhance T cell response to generate HBV-specific CTLs efficiently in vitro. Ub, a marker of protein degradation, may promote the generation of peptides appropriate for major histocompatibility complex class I presentation. In the present study, the specific immune responses of the fusion protein Ub-HBcAg-CTP in BALB/c mice were evaluated and the underlying mechanisms were investigated. Results showed that Ub-HBcAg-CTP increased the anti-HBcAg titer and produced the cytokines IFN-γ and IL-2. This fusion protein also induced higher percentages of IFN-γ(+)CD8(+) cells and specific CTL responses. Ub-HBcAg-CTP could also upregulate the expressions of Jak2, Tyk2, STAT1, and STAT4 in T lymphocytes. In conclusion, Ub-HBcAg-CTP enhanced cellular and humoral immune responses and induced robust HBV-specific CTL activities in BALB/c mice. PMID:25135878

  2. Suppression of USP18 Potentiates the Anti-HBV Activity of Interferon Alpha in HepG2.2.15 Cells via JAK/STAT Signaling

    PubMed Central

    Li, Lin; Lei, Qing-song; Zhang, Shu-Jun; Kong, Ling-na; Qin, Bo

    2016-01-01

    Ubiquitin-specific protease 18 (USP18, also known as UBP43) has both interferon stimulated gene 15 (ISG15) dependent and ISG15-independent functions. By silencing the expression of USP18 in HepG2.2.15 cells, we studied the effect of USP18 on the anti-HBV activity of IFN-α and demonstrated that knockdown of USP18 significantly Inhibited the HBV expression and increased the expression of ISGs. Levels of hepatitis B virus surface antigen (HBsAg), hepatitis B virus e antigen (HBeAg), HBV DNA and intracellular hepatitis B virus core antigen (HBcAg) were dramatically decreased with or without treatment of indicated dose of IFN-α. Suppression of USP18 activated the JAK/STAT signaling pathway as shown by the increased and prolonged expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT1) in combination with enhanced expression of several interferon stimulated genes (ISGs). Our results indicated that USP18 modulates the anti-HBV activity of IFN-α via activation of the JAK/STAT signaling pathway in Hepg2.2.15 cells. PMID:27227879

  3. Prevalence, attitudes and knowledge about HIV HBV and HCV infections among inmates in prisons Prilep and Bitola--a pilot study.

    PubMed

    Jovanovska, Tanja; Kocic, Biljana; Stojcevska, Viktorija P

    2014-06-01

    Prisons are associates as facilities liable of high risk of infection disease, as a result of the possibility of transmission of infections in prisons surroundings. Investigations carried out in correctional facilities around the world have shown a high prevalence of blood borne hepatitis viruses and HIV. The study was aimed at confirming prevalence of HIV hepatitis B and hepatitis C among prisoners in Bitola's, and Prilep's prisons, existing of co-infection as well to assess knowledge and attitudes related to HIV, HBV and HCV infections. In this cross-sectional study 200 prisoners have participated, providing answers to structured questionnaire and in order to analyze blood for HIV, HBV and HCV, rapid blood tests in detecting antibodies has been used. Prevalence of HCV is 0.20, HBV 0.17 and HIV prevalence is 0. Co-infection prevalence of HCV/HBV is 0.07 from the total number of examinees. As for the manner of infection with HIV virus 22% are familiar with the fact that persons cannot be infected by HIV if they have only one sexual partner who is not infected and have no other partners, and for the protection of HIV and Hepatitis B by correct use of condoms-58% have given correct answers. PMID:25144968

  4. HBX Protein-Induced Downregulation of microRNA-18a is Responsible for Upregulation of Connective Tissue Growth Factor in HBV Infection-Associated Hepatocarcinoma

    PubMed Central

    Liu, Xiaomin; Zhang, Yingjian; Wang, Ping; Wang, Hongyun; Su, Huanhuan; Zhou, Xin; Zhang, Lamei

    2016-01-01

    Background This study was designed to improve our understanding of the role of miR-18a and its target (connective tissue growth factor (CTGF), which are mediators in HBX-induced hepatocellular carcinoma (HCC). Material/Methods We first investigated the expression of several candidate microRNAs (miRNAs) reported to have been aberrantly expressed between HepG2 and HepG2.2.15, which is characterized by stable HBV infection, while the CTGF is identified as a target of miR-18a. Furthermore, the expression of CTGF evaluated in HepG2 was transfected with HBX, while the HepG2.2.15 was transfected with miR-18a and CTGF siRNA. We examined the cell cycle at the same time. Results We found that the expression of miR-18a was abnormally reduced in the HBV-positive HCC tissue samples compared with HBV-negative HCC samples. Through the use of a luciferase reporter system, we also identified CTGF 3′UTR (1046–1052 bp) as the exact binding site for miR-18a. We also observed a clear increase in CTGF mRNA and protein expression levels in HBV-positive HCC human tissue samples in comparison with the HBV-negative controls, indicating a possible negatively associated relationship between miR-18a and CTGF. Furthermore, we investigated the effect of HBX overexpression on miR-18a and CTGF, as well as the viability and cell cycle status of HepG2 cells. In addition, we found that HBX introduction downregulated miR-18a, upregulated CTGF, elevated the viability, and promoted cell cycle progression. We transfected HepG2.2.15 with miR-18a mimics and CTGF siRNA, finding that upregulated miR-18a and downregulated CTGF suppress the viability and cause cell cycle arrest. Conclusions Our study shows the role of the CTGF gene as a target of miR-18a, and identifies the function of HBV/HBX/miR-18a/CTGF as a key signaling pathway mediating HBV infection-induced HCC. PMID:27421245

  5. 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

  6. HIV, HCV, HBV, HSV, and syphilis prevalence among female sex workers in Tehran, Iran, by using respondent-driven sampling.

    PubMed

    Moayedi-Nia, Saeedeh; Bayat Jozani, Zahra; Esmaeeli Djavid, Gholamreza; Entekhabi, Fatemeh; Bayanolhagh, Saeed; Saatian, Minoo; Sedaghat, Abbas; Nikzad, Rana; Jahanjoo Aminabad, Fatemeh; Mohraz, Minoo

    2016-04-01

    To find out the prevalence of HIV, HCV, HBV, HSV, and syphilis infections among female sex workers (FSWs) in Tehran, a cross-sectional study by using respondent-driven sampling (RDS) method was conducted. From December 2012 to April 2013 FSWs in Tehran were recruited. Inclusion criteria consisted of trading sex during the 12 months prior to this study and selling sex for at least 6 months in participants' lifetime. Among 161 consenting participants, 5% were infected with HIV. Moreover, 8.1% of FSWs were HCV positive, 37.9% were of HSV type1/type2, 1.2% of participants were infected with HBV, and none of the participants were infected with syphilis. HIV-positive participants were significantly more likely to be co-infected with HSV type1/type2, be younger, have more sexual partners and especially more clients during seven days prior to this study and report more history of having at least one of sexually transmitted infections symptoms in 12 months prior the study. In the multiple logistic regression analysis, being infected with HSV and also being under 25 years of age were found to be independently associated with HIV infection. Compared with the prevalence of HIV among general population of Tehran, relatively high prevalence of HIV and other viral infections among FSWs should be considered. All in all, it is critical to commence effective counter-measures for this high-risk group if the aim is to prevent spreading of these viruses to general population. PMID:26565671

  7. Evaluation of a novel commercial quaternary ammonium compound for eradication of Mycobacteria, HCV and HBV in Egypt.

    PubMed

    Elkholy, Yasmine Samy; Hegab, Asmaa Sayed; Ismail, Dalia Kadry; Hassan, Reem Mostafa

    2016-01-01

    Endoscopes are a common source of outbreaks of healthcare-associated infections. It is therefore important to identify high-level disinfectants capable of eliminating or killing all vegetative bacteria, mycobacteria, and viruses. Aldehydebased disinfectants are most commonly used in clinical practice but resistance has recently been detected and side effects associated with these disinfectants are well documented. In this study, we evaluated Virusolve+® EDS, a novel quaternary ammonium compound formulation supplied by Amity international, against Mycobacterium bovis (ATCC-27289), hepatitis C virus (HCV)-positive serum and hepatitis B surface antigen-positive serum. We also compared its efficacy against Cidex® (glutaraldehyde 2%), an aldehyde-based disinfectant. M. bovis showed no growth after 10 weeks with either Virusolve+® or Cidex®. Virusolve+® achieved a 10(4)- fold reduction in the initial 10(6) HCV load under clean conditions (without red blood cells) for 20 min, whereas Cidex® achieved this reduction under clean and dirty conditions (without and with red blood cells, respectively) after both 10 and 20 min. Both Virusolve+® and Cidex® were able to eradicate hepatitis B virus (HBV) infectivity under clean conditions after 10 and 20 min, whereas under dirty conditions they were only able to eradicate virus infectivity after 20 min. Virusolve+® EDS when compared with Cidex® showed equal mycobactericidal activity completely eradicating M. bovis. However, both showed comparable virucidal activity against HBV, which was more effective under clean conditions, emphasizing the importance of the cleaning step in endoscope reprocessing. Cidex® was more effective at eradicating HCV under dirty conditions after a short contact time. PMID:26727900

  8. Rapid screening and identification of dominant B cell epitopes of HBV surface antigen by quantum dot-based fluorescence polarization assay

    NASA Astrophysics Data System (ADS)

    Meng, Zhongji; Song, Ruihua; Chen, Yue; Zhu, Yang; Tian, Yanhui; Li, Ding; Cui, Daxiang

    2013-03-01

    A method for quickly screening and identifying dominant B cell epitopes was developed using hepatitis B virus (HBV) surface antigen as a target. Eleven amino acid fragments from HBV surface antigen were synthesized by 9-fluorenylmethoxy carbonyl solid-phase peptide synthesis strategy, and then CdTe quantum dots were used to label the N-terminals of all peptides. After optimizing the factors for fluorescence polarization (FP) immunoassay, the antigenicities of synthetic peptides were determined by analyzing the recognition and combination of peptides and standard antibody samples. The results of FP assays confirmed that 10 of 11 synthetic peptides have distinct antigenicities. In order to screen dominant antigenic peptides, the FP assays were carried out to investigate the antibodies against the 10 synthetic peptides of HBV surface antigen respectively in 159 samples of anti-HBV surface antigen-positive antiserum. The results showed that 3 of the 10 antigenic peptides may be immunodominant because the antibodies against them existed more widely among the samples and their antibody titers were higher than those of other peptides. Using three dominant antigenic peptides, 293 serum samples were detected for HBV infection by FP assays; the results showed that the antibody-positive ratio was 51.9% and the sensitivity and specificity were 84.3% and 98.2%, respectively. In conclusion, a quantum dot-based FP assay is a very simple, rapid, and convenient method for determining immunodominant antigenic peptides and has great potential in applications such as epitope mapping, vaccine designing, or clinical disease diagnosis in the future.

  9. HBV polymerase overexpression due to large core gene deletion enhances hepatoma cell growth by binding inhibition of microRNA-100

    PubMed Central

    Huang, Ya-Hui; Tseng, Ying-Hsin; Lin, Wey-Ran; Hung, George; Chen, Tse-Ching; Wang, Tong-Hong; Lee, Wei-Chen; Yeh, Chau-Ting

    2016-01-01

    Different types of hepatitis B virus (HBV) core gene deletion mutants were identified in chronic hepatitis B patients. However, their clinical roles in different stages of natural chronic HBV infection remained unclear. To address this issue, HBV core genes were sequenced in three gender- and age-matched patient groups diagnosed as chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC), respectively. Functional analysis of the identified mutants was performed. A novel type of large-fragment core gene deletion (LFCD) was identified exclusively in HCC patients and significantly associated with unfavorable postoperative survival. The presence of LFCDs resulted in generation of precore-polymerase fusion protein or brought the polymerase reading frame under direct control of HBV precore/core promoter, leading to its over-expression. Enhanced cell proliferation and increased tumorigenicity in nude mice were found in hepatoma cells expressing LFCDs. Because of the epsilon-binding ability of HBV polymerase, we hypothesized that the over-expressed polymerase carrying aberrant amino-terminal sequence could bind to cellular microRNAs. Screening of a panel of microRNAs revealed physical association of a precore-polymerase fusion protein with microRNA-100. A binding inhibition effect on microRNA-100 by the precore-polymerase fusion protein with up-regulation of its target, polo-like kinase 1 (PLK1), was discovered. The binding inhibition and growth promoting effects could be reversed by overexpressing microRNA-100. Together, HCC patients carrying hepatitis B large-fragment core gene deletion mutants had an unfavorable postoperative prognosis. The growth promoting effect was partly due to polymerase overexpression, leading to binding inhibition of microRNA-100 and up-regulation of PLK1. PMID:26824500

  10. 31 CFR 50.93 - Application of pro rata share.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Application of pro rata share. 50.93... PROGRAM Cap on Annual Liability § 50.93 Application of pro rata share. An insurer shall apply the PRLP to determine the pro rata share of each insured loss to be paid by the insurer on all insured losses...

  11. 26 CFR 1.1377-1 - Pro rata share.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 11 2011-04-01 2011-04-01 false Pro rata share. 1.1377-1 Section 1.1377-1...) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1377-1 Pro rata share. (a) Computation of pro rata shares—(1) In general. For purposes of subchapter S of chapter 1 of the...

  12. 31 CFR 50.93 - Application of pro rata share.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Application of pro rata share. 50.93... PROGRAM Cap on Annual Liability § 50.93 Application of pro rata share. An insurer shall apply the PRLP to determine the pro rata share of each insured loss to be paid by the insurer on all insured losses...

  13. Cryogenic system for BERLinPro

    NASA Astrophysics Data System (ADS)

    Anders, W.; Hellwig, A.; Knobloch, J.; Pflückhahn, D.; Rotterdam, S.

    2014-01-01

    In 2010 Helmholtz-Zentrum Berlin (HZB) received funding to design and build the Berlin Energy Recovery Linac Project BERLinPro. The goal of this compact Energy recovery linac (ERL) is to develop the accelerator physics and technology required to generate and accelerate a 100-mA, 1-mm mrad emittance electron beam. The BERLinPro know-how can then be transferred to various ERL-based applications. All accelerating RF cavities including the electron source are based on superconducting technology operated at 1.8 K. A Linde L700 helium liquefier is supplying 4.5 K helium. The subatmospheric pressure of 16 mbar of the helium bath of the cavities will be achieved by pumping with a set of cold compressors and warm vacuum pumps. While the L700 is already in operating, the 1.8 K system and the helium transfer system are in design phase.

  14. [Radiation Anticarcinogenesis by Thiazolidine Pro-drug

    NASA Technical Reports Server (NTRS)

    Warters, Raymond L.; Roberts, Jeanette C.; Fain, Heidi

    1999-01-01

    The original goal of this work was to determine the capacity of selected aminothiols to modulate radiation induced cytotoxicity, mutagenesis and carcinogenesis in a human mammary epithelial cell line. The conclusions from this work are that WR-1065 is the "gold standard" for protection against radiation induced cytotoxicity, mutagenesis and carcinogenesis. While a potent radiation protector, WR-1065 is cytotoxic in vitro and in vivo. Our rationale for a study of the thiazolidine pro-drugs was that these compounds are neither toxic in vitro or in vivo. The results obtained during this funding period indicate that the thiazolidine pro-drugs are as potent as WR-1065 as protectors against radiation induced mutation induction, and thus presumably against radiation induced carcinogenesis. Our results indicate that the thiazolidine prodrugs are excellent candidates to test as non-toxic anticarcinogens for protecting astronauts from cancer induction during space travel.

  15. The ProSeal laryngeal mask airway.

    PubMed

    Brimacombe, Joseph; Keller, Christian

    2002-12-01

    The ProSeal LMA is a major advance over the Classic LMA because of the following reasons: it allows ventilation at much higher airway pressures; it protects the lungs from aspiration and the stomach from gastric insufflation; it facilitates passage of a gastric tube and monitoring devices into the esophagus; it can be inserted like the Classic or Intubating LMA; it has its own built-in bite block; malposition is detected more readily; and, through use of techniques such as gum elastic bougie-guided insertion, correct positioning is almost guaranteed. The ProSeal can be considered a replacement device for the Classic LMA, but the Flexible LMA is still preferable for most intraoral procedures, and the Intubating LMA is still preferable whenever intubation is required. Limitations are that it is slightly more difficult to insert and requires more careful thought to use optimally. PMID:12512267

  16. Cryogenic system for BERLinPro

    SciTech Connect

    Anders, W.; Hellwig, A.; Knobloch, J.; Pflückhahn, D.; Rotterdam, S.

    2014-01-29

    In 2010 Helmholtz-Zentrum Berlin (HZB) received funding to design and build the Berlin Energy Recovery Linac Project BERLinPro. The goal of this compact Energy recovery linac (ERL) is to develop the accelerator physics and technology required to generate and accelerate a 100-mA, 1-mm mrad emittance electron beam. The BERLinPro know-how can then be transferred to various ERL-based applications. All accelerating RF cavities including the electron source are based on superconducting technology operated at 1.8 K. A Linde L700 helium liquefier is supplying 4.5 K helium. The subatmospheric pressure of 16 mbar of the helium bath of the cavities will be achieved by pumping with a set of cold compressors and warm vacuum pumps. While the L700 is already in operating, the 1.8 K system and the helium transfer system are in design phase.

  17. Cognitive Obstacles to Pro-Vaccination Beliefs.

    PubMed

    Miton, Helena; Mercier, Hugo

    2015-11-01

    Two frameworks--cultural attraction theory and epistemic vigilance--predict a cultural disadvantage for counter-intuitive beliefs. We review several cognitive mechanisms that conspire to render pro-vaccination beliefs counter-intuitive. Trust and argumentation can spread counter-intuitive beliefs, but only under some conditions. We discuss the hurdles that trust and argumentation face in the case of vaccination. PMID:26522341

  18. Some problems with pro-competition reforms.

    PubMed

    Agich, G J; Begley, C E

    1985-01-01

    As the search for effective cost-containment policies continues, health care reform along pro-competition lines has gained considerable backing in the United States. By offering market competition to achieve allocational efficiency and vouchers and tax credits to achieve distributional equity, pro-competition reforms appear to satisfy what many believed were incommensurable goals. A critical review of this strategy reveals two practical difficulties, however. The first concerns the ambiguity arising from the proposals' reliance on the concept of equal access to some basic level of health care as its distributional objective and the second concerns the ethical dilemma arising from the proposals' reliance on physicians as rationers of health care. In considering the distributional goal of guaranteeing access to a basic minimum of health care, we argue that, despite its theoretical attractiveness, there exists no acceptable way of determining or justifying its content, and without a clear definition of the basic minimum there is no guarantee that any equity objective will be achieved under the pro-competition strategy. With regard to the use of physicians and other providers as society's gatekeepers, we point out that this role is in direct conflict with traditional responsibilities that patients expect providers to assume. Requiring doctors to ration services in response to market incentives may further erode the trust relationship between physicians and patients, and clearly puts the more seriously ill at a disadvantage. PMID:4059946

  19. Calibrating the Prominence Magnetometer (ProMag)

    NASA Astrophysics Data System (ADS)

    Fox, Lewis; Casini, R.

    2013-07-01

    The Prominence Magnetometer (ProMag) is a dual-channel, dual-beam, slit-scanning, full Stokes spectro-polarimeter designed by the High Altitude Observatory at the National Center for Atmospheric Research (HAO/NCAR) for the study of the magnetism of solar prominences and filaments. It was deployed in August 2009 at the 40 cm coronagraph of the Evans Solar Facility (ESF) of the National Solar Observatory on Sacramento Peak (NSO/SP). In its standard mode of operation it acquires spectro-polarimetric maps of solar targets simultaneously in the two chromospheric lines of He I at 587.6 nm and 1083.0 nm. Since August 2011 ProMag has operated in “patrol mode” with a dedicated observer. We aim to routinely measure the vector magnetic field in prominences. The electro-optic modulator and polarization analyzer are integrated into a single mechanical unit located at the coude feed of the telescope. This location was necessary for proper co-alignment of the dual beams, but complicates the precise polarimeter calibration necessary to achieve the sensitivity required for prominence measurements (< 10^-3). At this sensitivity, small variations in optical alignment can become significant. We present a calibration method for ProMag, using a polarizer and retarder at coronagraph prime focus. Calibrations are recorded before and after observations. We discuss the success of this method and its limitations.

  20. Perl Embedded in PTC's Pro/ENGINEER, Version 1

    SciTech Connect

    2003-12-22

    Pro-PERL (AKA Pro/PERL) is a Perl extension to the PTC Pro/TOOLKIT API to the PTC Pro/ENGINEER CAD application including an embedded interpreter. It can be used to automate and customize Pro/ENGINEER, create Vendor Neutral Archive (VNA) format files and re-create CAD models from the VNA files. This has applications in sanitizing classified CAD models created in a classified environment for transfer to an open environment, creating template models for modification to finished models by non-expert users, and transfer of design intent data to other modeling technologies.

  1. Perl Embedded in PTC's Pro/ENGINEER, Version 1

    Energy Science and Technology Software Center (ESTSC)

    2003-12-22

    Pro-PERL (AKA Pro/PERL) is a Perl extension to the PTC Pro/TOOLKIT API to the PTC Pro/ENGINEER CAD application including an embedded interpreter. It can be used to automate and customize Pro/ENGINEER, create Vendor Neutral Archive (VNA) format files and re-create CAD models from the VNA files. This has applications in sanitizing classified CAD models created in a classified environment for transfer to an open environment, creating template models for modification to finished models by non-expertmore » users, and transfer of design intent data to other modeling technologies.« less

  2. Potential risks of pro-eating disorder websites.

    PubMed

    Rouleau, Codie R; von Ranson, Kristin M

    2011-06-01

    Although dangers of pro-eating disorder (pro-ED) websites have recently been discussed in the popular press, no integration of research findings on this topic yet exists. After completing a systematic search for peer-reviewed articles about pro-ED websites, we identified three possible risks as themes: operation under the guise of "support," reinforcement of disordered eating, and prevention of help-seeking and recovery. Pro-ED websites tend to be perceived as supportive by users, but instead appear to exacerbate or maintain users' eating disorder symptoms. We discuss research and clinical implications of these dangers. Future research should clarify how specific features of pro-ED websites contribute to the development, exacerbation, and maintenance of eating pathology, e.g., by employing experimental techniques and prospective designs with clinical samples and various ages. Despite limited empirical research on the topic, existing findings should prompt clinicians, parents, and researchers to remain vigilant about potential negative influences of pro-ED websites on users. PMID:21272967

  3. BDNF pro-peptide regulates dendritic spines via caspase-3.

    PubMed

    Guo, J; Ji, Y; Ding, Y; Jiang, W; Sun, Y; Lu, B; Nagappan, G

    2016-01-01

    The precursor of brain-derived neurotrophic factor (BDNF) (proBDNF) is enzymatically cleaved, by either intracellular (furin/PC1) or extracellular proteases (tPA/plasmin/MMP), to generate mature BDNF (mBDNF) and its pro-peptide (BDNF pro-peptide). Little is known about the function of BDNF pro-peptide. We have developed an antibody that specifically detects cleaved BDNF pro-peptide, but not proBDNF or mBDNF. Neuronal depolarization elicited a marked increase in extracellular BDNF pro-peptide, suggesting activity-dependent regulation of its extracellular levels. Exposure of BDNF pro-peptide to mature hippocampal neurons in culture dramatically reduced dendritic spine density. This effect was mediated by caspase-3, as revealed by studies with pharmacological inhibitors and genetic knockdown. BDNF pro-peptide also increased the number of 'elongated' mitochondria and cytosolic cytochrome c, suggesting the involvement of mitochondrial-caspase-3 pathway. These results, along with BDNF pro-peptide effects recently reported on growth cones and long-term depression (LTD), suggest that BDNF pro-peptide is a negative regulator of neuronal structure and function. PMID:27310873

  4. The pro-adhesive and pro-survival effects of glucocorticoid in human ovarian cancer cells.

    PubMed

    Yin, Lijuan; Fang, Fang; Song, Xinglei; Wang, Yan; Huang, Gaoxiang; Su, Jie; Hui, Ning; Lu, Jian

    2016-07-01

    Cell adhesion to extracellular matrix (ECM) is controlled by multiple signaling molecules and intracellular pathways, and is pivotal for survival and growth of cells from most solid tumors. Our previous works demonstrated that dexamethasone (DEX) significantly enhances cell adhesion and cell resistance to chemotherapeutics by increasing the levels of integrin β1, α4, and α5 in human ovarian cancer cells. However, it is unclear whether the components of ECM or other membrane molecules are also involved in the pro-adhesive effect of DEX in ovarian cancer cells. In this study, we demonstrated that the treatment of cells with DEX did not change the expression of collagens (I, III, and IV), laminin, CD44, and its principal ligand hyaluronan (HA), but significantly increased the levels of intracellular and secreted fibronectin (FN). Inhibiting the expression of FN with FN1 siRNA or blocking CD44, another FN receptor, with CD44 blocking antibody significantly attenuated the pro-adhesion of DEX, indicating that upregulation of FN mediates the pro-adhesive effect of DEX by its interaction with CD44 besides integrin β1. Moreover, DEX significantly enhanced cell resistance to the chemotherapeutic agent paclitaxel (PTX) by activating PI-3K-Akt pathway. Finally, we found that DEX also significantly upregulated the expression of MUC1, a transmembrane glycoprotein. Inhibiting the expression of MUC1 with MUC1 siRNA significantly attenuated the DEX-induced effects of pro-adhesion, Akt-activation, and pro-survival. In conclusion, these results provide new data that upregulation of FN and MUC1 by DEX contributes to DEX-induced pro-adhesion and protects ovarian cancer cells from chemotherapy. PMID:27151574

  5. The Diagnostic Accuracy and Clinical Utility of Three Noninvasive Models for Predicting Liver Fibrosis in Patients with HBV Infection

    PubMed Central

    Zhang, Zhiqiao; Wang, Gongsui; Kang, Kaifu; Wu, Guobiao; Wang, Peng

    2016-01-01

    Aim To evaluate the diagnostic accuracy and clinical utility of the fibrosis index based on the four factors (FIB-4), aspartate aminotransferase -to-platelet ratio index (APRI), and aspartate aminotransferase–alanine aminotransferase ratio index (AAR) for predicting liver fibrosis in patients with HBV infection. Methods From January 2006 to December 2010,a total of 1543 consecutive chronic hepatitis B(CHB) patients who underwent liver biopsies were enrolled. FIB-4,APRI, and AAR were calculated.The areas under the receiver-operating characteristic curves (AUROCs) were calculated to assess the diagnostic accuracy of these models.The AUROCs of these models were compared by DeLong’s test.For further comparisons in different studies,the AUROCs were adjusted to conduct Adjusted AUROCs(ADjAUROCs) according to the prevalence of fibrosis stages using the difference between advanced and nonadvanced fibrosis (DANA). Results For prediction of significant fibrosis,severe fibrosis,and cirrhosis,the AUROCs of FIB-4 were 0.646(ADjAUROC 0.717),0.670(ADjAUROC 0.741), and 0.715(ADjAUROC 0.786) respectively;whereas it were 0.656(ADjAUROC 0.727),0.653(ADjAUROC 0.724) and 0.639(ADjAUROC 0.710) for APRI, 0.498(ADjAUROC 0.569),0.548(ADjAUROC 0.619) and 0.573(ADjAUROC 0.644) for AAR. The further comparisons demonstrated that there were no significant differences of AUROCs between FIB-4 and APRI in predicting significant and severe fibrosis(P > 0.05),while FIB-4 was superior to APRI in predicting cirrhosis(P < 0.001). Further subgroup analysis demonstrated that the diagnostic accuracy of FIB-4 and APRI in patients with normal alanine aminotransferase(ALT) were higher than that in patients with elevated ALT. Conclusions The results demonstrated that FIB-4 and APRI are useful for diagnosis of fibrosis. FIB-4 and APRI have similar diagnostic accuracy in predicting significant and severe fibrosis,while FIB-4 is superior to APRI in predicting cirrhosis. The clinical utility of FIB-4 and APRI

  6. Derived neutrophil to lymphocyte ratio predicts prognosis for patients with HBV-associated hepatocellular carcinoma following transarterial chemoembolization

    PubMed Central

    ZHOU, DONGSHENG; LIANG, JIANZHONG; XU, LI; HE, FENGYING; ZHOU, ZHONGGUO; ZHANG, YAOJUN; CHEN, MINSHAN

    2016-01-01

    The derived neutrophil to lymphocyte ratio (dNLR) has been proposed as an easily determinable prognostic factor for cancer patients, but the prognostic significance of the dNLR in hepatocellular carcinoma (HCC) has not been investigated. The present study aimed to validate the prognostic power of the NLR and dNLR in HCC patients undergoing transarterial chemoembolization (TACE). The data of 279 consecutive patients who underwent TACE for unresectable HBV-associated HCC between September 2009 and November 2011 at the Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center (Guangzhou, China) were retrieved from a prospective database. The cut-off values for the NLR and dNLR were determined by receiver operating characteristic (ROC) analysis. The association between the NLR and dNLR and the clinicopathological characteristics and overall survival (OS) rates and times of patients was analyzed. The area under the curve (AUC) was calculated to evaluate the discriminatory ability of the NLR and dNLR. The median follow-up period was 446 days, the 1, 2 and 3-year OS rates were 38.8, 18.5 and 11.1% respectively, and the median OS time was 264 days. The cut-off values were determined as 2.6 and 1.8 for the NLR and dNLR, respectively. The NLR and dNLR were each associated with patient age, presence of vascular invasion, tumor size, AST level and ALP level. Multivariate analysis showed that the NLR, dNLR, ALT level and AFP level were independent prognostic factors for OS. An elevated NLR or dNLR was associated with a poor prognosis (P=0.001 and P=0.002, respectively). The prognostic power of NLR [AUC=0.539; 95% confidence interval (CI), 0.423–0.656] and dNLR (AUC=0.522; 95% CI, 0.406–0.638) was similar. Elevated dNLR predicted poor prognosis for patients with HBV-associated HCC undergoing TACE, with similar prognostic power to NLR. The dNLR may be used as an alternative to the NLR, as it is easily available and inexpensive. PMID:27123051

  7. Sensitivity Analysis of a Conceptual HBV Raınfall-Runoff MODEL Using Eumetsat Snow Covered Area Product

    NASA Astrophysics Data System (ADS)

    Akyurek, Z.; Surer, S.; Parajka, J.

    2014-12-01

    HBV is a conceptual hydrological model extensively used in operational hydrological forecasting and water balance studies. In this study, we apply the HBV model on the upper Euphrates basin in Turkey, which has 10 624 km2 area. The Euphrates basin is largely fed from snow precipitation whereby nearly two-thirds occur in winter and may remain in the form of snow for half of the year. We analyze individual sensitivity of the parameters by calibrating the model using the Multi-Objective Shuffled Complex Evolution (MOSCEM) algorithm. The calibration is performed against snow cover area (SCA) in addition to runoff data for the water years 2009, 2010, 2011, 2012 and 2013. The SCA product has been developed in the framework of the European Organization for the Exploitation of Meteorological Satellites (EUMETSAT), Satellite Application Facility on Support to Operational Hydrology and Water Management (H-SAF) Project. The product is generated by using data from Spinning Enhanced Visible and InfraRed Imager (SEVIRI) instrument making observations from a geostationary satellite Meteosat Second Generation (MSG). In the previous study evaluation of the model was done with commonly used statistical performance metrics (Nash-Sutcliffe) for high and low flows, volume error and root mean square error (RMSE). In this study signature metrics, which are based on the flow duration curve (FDC) are used to see the performance of the model for low flows. In order to consider a fairly balanced evaluation between high and low flow phases we divided the flow duration curve into segments of high, medium and low flow phases, and additionally into very high and very low phases. Root mean square error (RMSE) is used to evaluate the performance in these segments. The sensitivity analysis of the parameters around the calibrated optimum points showed that parameters of the soil moisture and evapotranspiration (FC, beta and LPrat) have a strong effect in the total volume error of the model. The

  8. Educational Opportunities in Pro-Am Collaboration

    NASA Astrophysics Data System (ADS)

    Fienberg, R. T.; Stencel, R. E.

    2006-08-01

    While many backyard stargazers take up the hobby just for fun, many others are attracted to it because of their keen interest in learning more about the universe. The best way to learn science is to do science. Happily, the technology available to today's amateur astronomers — including computer-controlled telescopes, CCD cameras, powerful astronomical software, and the Internet — gives them the potential to make real contributions to scientific research and to help support local educational objectives. Meanwhile, professional astronomers are losing access to small telescopes as funding is shifted to larger projects, including survey programs that will soon discover countless interesting objects needing follow-up observations. Clearly the field is ripe with opportunities for amateurs, professionals, and educators to collaborate. Amateurs will benefit from mentoring by expert professionals, pros will benefit from observations and data processing by increasingly knowledgeable amateurs, and educators will benefit from a larger pool of skilled talent to help them carry out astronomy-education initiatives. We will look at some successful pro-am collaborations that have already borne fruit and examine areas where the need and/or potential for new partnerships is especially large. In keeping with the theme of this special session, we will focus on how pro-am collaborations in astronomy can contribute to science education both inside and outside the classroom, not only for students of school age but also for adults who may not have enjoyed particularly good science education when they were younger. Because nighttime observations with sophisticated equipment are not always possible in formal educational settings, we will also mention other types of pro-am partnerships, including those involving remote observing, data mining, and/or distributed computing.

  9. Human herpesvirus-6 has no apparent influence on course of HCV hepatitis, but may complicate HBV hepatitis and alcoholic liver disease. A pilot study.

    PubMed

    Rojo, Julieta; Simoes, Patricia; Krueger, Gerhard R F; Humberto, Cruz Ortiz; Ramon, Albert M

    2003-01-01

    Human herpesvirus-6 (HHV-6) is a widespread virus with occasional reactivation and a potential hepatotropism. The present study was undertaken to investigate the frequency of HHV-6 reactivation in viral (HCV, HBV) and alcoholic liver diseases and its implication for the course of the primary disease. Serological and immunohistochemical tests were done to document viral activity, hepatocellular apoptosis or proliferation, and autoantibody formation. While the course of HCV remains apparently uninfluenced by HHV-6, HBV hepatitis and alcoholic liver disease show a higher incidence of autoantibody formation if HHV-6 is present. The data of this pilot study warrant more extensive investigations of the clinical pathology of HHV-6 in liver diseases. PMID:12655786

  10. Prevalence, correlates and pattern of Hepatitis B among antenatal clinic attenders in Yaounde-Cameroon: is perinatal transmission of HBV neglected in Cameroon?

    PubMed Central

    2013-01-01

    Background Few studies have evaluated the prevalence of HBV in the general Cameroonian population or among antenatal attendants. The aim of this study was to determine the prevalence, correlates and patterns of Hepatitis B surface antigen among pregnant women attending antenatal care in Yaounde-Cameroon. Methods This was a cross-sectional multicenter study carried out in a referral hospital and two secondary hospitals in Yaounde, the capital of Cameroon. The study lasted 15 months (March 2011 to June 2012), and recruited 959 pregnant women. Patient recruitment was consecutive. The HBsAg was tested using the Monalisa HBsAg Ultra ELISA kit. Other hepatitis B markers were equally tested. We used the statistical package for social sciences (SPSS) version 14.0 software to conduct a quantitative analysis of the derived data. Simple descriptive statistics such as means, standard deviations, and proportions were used to describe the data. We tested for association in categorical variables using the chi-squared (χ2) test. The odds ratio (OR) and the corresponding 95% confidence intervals (95% CI) were used to summarise the strength of association between specific binary exposure and outcome variables. The level of statistical significance for the study was set at p < 0.05. Results The prevalence of hepatitis B infection (HBsAg) among antenatal clinic attenders in our setting was 7.7%. Amongst these women, just 5.4% were previously aware of their HBsAg status. The rate of HBV infectivity was high, with 28% of HBsAg positive women having evidence of HBeAg in their plasma, and up to 45.8% of these women lacking antibodies against hepatitis B e antigen (anti-HBe). About 41% of the pregnant women had had previous contact with HBV as evidenced by the positive status for anti-HBc. Just 2.7% of the pregnant women had previously been vaccinated against HBV. The mean age for HBsAg positivity in our setting was 26.9 ±4.7 years, and the most affected age group was the 25 – 29

  11. Feasibility of combining adjuvant transarterial chemoembolization with nucleos(t)ide analog therapy for patients with HBV-associated hepatocellular carcinoma after hepatectomy

    PubMed Central

    GONG, WEN-FENG; ZHONG, JIAN-HONG; XIANG, BANG-DE; LI, LE-QUN

    2016-01-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortalities, and its prevalence is expected to increase in future decades. Hepatitis B virus (HBV) infection is the leading cause of HCC. Although hepatectomy is the preferred curative treatment for HCC, tumor recurrence is common, which is the most frequent cause of mortality in patients with HCC. HCC recurrence may originate from the primary tumor or be associated with remnant liver tissue, and include high viral load and hepatic inflammatory activity. Adjuvant transarterial chemoembolization and postoperative nucleos(t)ide analogs therapy are the two corresponding therapies. Following systematic searching of the PubMed database, the indications for adjuvant transarterial chemoembolization and nucleos(t)ide analog therapies for HBV-related HCC after hepatectomy were acquired. Additionally, the feasibility of combining these two therapies were also reviewed. PMID:27330754

  12. The utility of Pro Forma Income Statements.

    PubMed

    Reiboldt, Max; Reiboldt, John

    2002-01-01

    Recent headlines surrounding the financial demise of the nation's seventh largest company, Enron, and its subsequent entanglements with its accounting and consulting firm, Arthur Andersen, have placed a cloud of suspicion upon many reasonable business practices that otherwise are considered standard procedure. The proforma income statement is one of those practices. An oft-used tool in financial management, pro formas play a useful role for projecting financial performance based on predictable forecasts or assumptions. Regardless of the current scrutiny, there is still a valid use for accurately prepared statements. PMID:12389329

  13. [Analysis of the results of the HIV-1, HCV and HBV viral load of SEIMC External Quality Control Program. Year 2014].

    PubMed

    Medina González, Rafael; Orta Mira, Nieves; Guna Serrano, María Del Remedio; Latorre Martínez, José-Carlos; Gopegui, Enrique Ruiz de; Rosario Ovies, María; Poveda, Marta; Gimeno Cardona, Concepción

    2016-07-01

    Human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarizes the results obtained from the 2014 SEIMC (Spanish Society of Infectious Diseases and Clinical Microbiology) External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of 5 standards were sent. One standard consisted in seronegative human plasma, while the remaining 4 contained plasma from 3 different viremic patients, in the range of 2-5 log10 copies/mL; 2 of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (30.8% on average) obtained values out of the accepted range (mean ± 0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 95.8% of laboratories reporting results within the limits (Δ < 0.5 log10 copies/mL). The HBV and HCV program consisted of 2 standards with different viral load contents. Most of the participants, 83.7% in the case of HCV and 87.9% in the HBV, obtained all the results within the accepted range (mean ± 1.96 standard deviations log10 IU/mL). Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up. PMID:27474241

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

    PubMed

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

    2015-09-01

    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

  15. [Analysis of the results of the HIV-1, HCV and HBV viral load of SEIMC External Quality Control Program. Year 2013].

    PubMed

    Orta Mira, Nieves; Del Remedio Guna Serrano, María; Latorre Martínez, José-Carlos; Medina González, Rafael; Rosario Ovies, María; Poveda, Marta; Ruiz de Gopegui, Enrique; Gimeno Cardona, Concepción

    2015-07-01

    Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarized the results obtained from the 2013 SEIMC External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted in seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 2-5 log10 copies/mL; two of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (25% on average) obtained values out of the accepted range (mean ± 0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 98.9% of laboratories reporting results within the limits (D < 0.5 log10 copies/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 82% in the case of HCV and 78% in the HBV, obtained all the results within the accepted range (mean ± 1.96 SD log10 UI/mL). Data from this analysis reinforce the utility of proficiency programmes to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up. PMID:26320990

  16. Osteopontin and latent-TGF β binding-protein 2 as potential diagnostic markers for HBV-related hepatocellular carcinoma.

    PubMed

    da Costa, Andre Nogueira; Plymoth, Amelie; Santos-Silva, Daniela; Ortiz-Cuaran, Sandra; Camey, Suzy; Guilloreau, Paule; Sangrajrang, Suleeporn; Khuhaprema, Thiravud; Mendy, Maimuna; Lesi, Olufunmilayo A; Chang, Hee-Kyung; Oh, Jin-Kyoung; Lee, Duk-Hee; Shin, Hai-Rim; Kirk, Gregory D; Merle, Philippe; Beretta, Laura; Hainaut, Pierre

    2015-01-01

    Chronic Hepatitis B (HB) is the main risk factor for chronic liver disease (CLD) and hepatocellular carcinoma (HCC) in many low-resource countries, where diagnosis is constrained by lack of clinical, histopathological and biomarker resources. We have used proteomics to detect plasma biomarkers that outperform α-Fetoprotein (AFP), the most widely used biomarker for HCC diagnosis in low-resource contexts. Deep-plasma proteome analysis was performed in HCC patients, patients with CLD and in HB-carrier controls from Thailand (South-East Asia) and The Gambia (West-Africa). Mass spectrometry profiling identified latent-transforming growth factor β binding-protein 2 (LTBP2) and Osteopontin (OPN) as being significantly elevated in HCC versus CLD and controls. These two proteins were further analyzed by ELISA in a total of 684 plasma samples, including 183 HCC, 274 CLD and 227 asymptomatic controls. When combined, LTBP2 and OPN showed an area under the receiver operating curve of 0.85 in distinguishing HCC from CLD in subjects with AFP <20 ng/mL. In a prospective cohort of 115 CLD patients from Korea, increased plasma levels of LTBP2 and/or OPN were detected in plasma collected over 2 years prior to diagnosis in 21 subjects who developed HCC. Thus, the combination of LTBP2 and OPN outperformed AFP for diagnosis and prediction of HCC and may therefore improve biomarker-based detection of HBV-related HCC. PMID:24803312

  17. mTOR regulates TLR-induced c-fos and Th1 responses to HBV and HCV vaccines.

    PubMed

    He, Li; Zang, Aiping; Du, Min; Ma, Dapeng; Yuan, Chuanping; Zhou, Chun; Mu, Jing; Shi, Huanjing; Li, Dapeng; Huang, Xulin; Deng, Qiang; Xiao, Jianhua; Yan, Huimin; Hui, Lijian; Lan, Ke; Xiong, Sidong; Li, Xiaoxia; Huang, Zhong; Xiao, Hui

    2015-06-01

    Although IL-12 plays a critical role in priming Th1 and cytotoxic T lymphocyte (CTL) responses, Toll-like receptor (TLR) signaling only induces low amounts of IL-12 in dendritic cells and macrophages, implying the existence of stringent regulatory mechanisms. In this study, we sought to uncover the mechanisms underlying TLR-induced IL-12 expression and the Th1 response. By systemic screening, we identified a number of protein kinases involved in the regulation of TLRinduced IL-12 expression. In particular, PI3K, ERK, and mTOR play critical roles in the TLR-induced Th1 response by regulating IL-12 and IL-10 production in innate immune cells. Moreover, we identified c-fos as a key molecule that mediates mTOR-regulated IL-12 and IL-10 expression in TLR signaling. Mechanistically, mTOR plays a crucial role in c-fos expression, thereby modulating NFκB binding to promoters of IL-12 and IL-10. By controlling the expression of a special innate gene program, mTOR can specifically regulate the TLR-induced T cell response in vivo. Furthermore, blockade of mTOR by rapamycin efficiently boosted TLR-induced antigen-specific T and B cell responses to HBV and HCV vaccines. Taken together, these results reveal a novel mechanism through which mTOR regulates TLR-induced IL-12 and IL-10 production, contributing new insights for strategies to improve vaccine efficacy. PMID:26122641

  18. Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans.

    PubMed Central

    Vitiello, A; Ishioka, G; Grey, H M; Rose, R; Farness, P; LaFond, R; Yuan, L; Chisari, F V; Furze, J; Bartholomeuz, R

    1995-01-01

    Our goal is to use peptide epitopes that are recognized by cytotoxic T lymphocytes (CTL) as immunogens for the development of prophylactic and therapeutic vaccines with chronic hepatitis B virus (HBV) infection being our first therapeutic target. Because most CTL peptide epitopes are poor immunogens, we specifically modified them by covalently attaching two additional components: a T helper peptide epitope and two lipid molecules. Using the murine influenza virus CTL epitope NP 147-155 as a model system, we found this construct to be highly immunogenic, and a single injection resulted in memory CTL induction that persisted for > 1 yr. Based on the animal studies, a vaccine was designed and tested for both safety and its ability to induce a primary CTL response in normal subjects. The three vaccine components included HBV core antigen peptide 18-27 as the CTL epitope, tetanus toxoid peptide 830-843 as the T helper peptide, and two palmitic acid molecules as the lipids. A dose escalation trial (5, 50, and 500 micrograms) carried out in 26 normal subjects showed that the vaccine was safe and able to induce a primary HBV-specific CTL response. A dose-response curve was observed and five out of five subjects responded to the 500-micrograms dose. PMID:7814635

  19. The theoretical and practical knowledge of nurses and midwives regarding to the hepatitis-B virus (HBV) vaccination: a cross-sectional study in Konya--Turkey.

    PubMed

    Cetinkaya, Senay

    2014-03-01

    The aim of our cross-sectional study was to investigate the factors that affected Hepatitis-B Vaccination (HBV) knowledge of the nurses and midwives, serving at various medical facilities as part of the primary healthcare services in Konya, Turkey. The study was conducted during March 01-31, 2004, including 127 consentient nurses and midwives (out of 161) serving at 22 different healthcare centers in the region. In the survey, their source of information with regards to HBV vaccination varied from continuing education programs (37%) to book or brochure reading (11.8%), and their formal nursing education (11%). A statistically significant relationship was found between the number of years employed in this profession and knowledge of Hepatitis markers that are done prior to the beginning of vaccination calendar (p = 0.01) (p < 0.05). Majority (74.8%) of the participants reported that they gave information to families about potential side effects of HBV vaccination. In conclusion we have suggested that a special training program should be given to nurses and midwives that included topics like Hepatitis markers, vaccine administration techniques, doses, proper record taking, briefing individuals and families. PMID:24851596

  20. Evaluation of Antiviral Therapy Performed after Curative Therapy in Patients with HBV-Related Hepatocellular Carcinoma: An Updated Meta-Analysis

    PubMed Central

    Yuan, Peng; Chen, Peng; Qian, Yeben

    2016-01-01

    Background. The long-term prognosis after curative therapy for hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) remains unsatisfactory due to the high incidence of recurrence. The effect of treatment with nucleotide analogues (NAs) in patients with HBV-related HCC after curative therapy remains unclear. Objective. To assess the impact of using NAs after curative therapy. Method. A computerized literature search was performed; eligible studies were identified from databases. The pooled risk ratios (RRs) and 95% CIs were calculated using Review Manager 5.3. Result. The meta-analysis included a total of 15 studies with 8060 patients. The one-year and three-year recurrence (one-year recurrence: RR 0.41 [95% CI 0.28 to 0.61]; P < 0.00001; three-year recurrence: RR 0.63 [95% CI 0.43 to 0.94]; P = 0.001) and the one-, three-, and five-year overall survival (OS) and disease-free survival (DFS) were significantly better in the treatment group. Conclusion. NAs can reduce the recurrence and improve the prognosis of HBV-related HCC after curative therapy. PMID:27446846

  1. Managing HBV in pregnancy. Prevention, prophylaxis, treatment and follow-up: position paper produced by Australian, UK and New Zealand key opinion leaders.

    PubMed

    Visvanathan, Kumar; Dusheiko, Geoff; Giles, Michelle; Wong, May-Ling; Phung, Nghi; Walker, Susan; Le, Suong; Lim, Seng Gee; Gane, Ed; Ngu, Meng; Hardikar, Winita; Cowie, Ben; Bowden, Scott; Strasser, Simone; Levy, Miriam; Sasaduesz, Joe

    2016-02-01

    Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These include the lack of a current cohesive strategy for treatment and follow-up of mothers and their babies; the uncertain risk of postpartum HBV flares; the lack of randomised trial data on the safety and efficacy of antiviral treatment in pregnancy; the lack of head-to-head studies comparing different antivirals in pregnancy; and the lack of epidemiologic information regarding infection across different populations globally. This position paper provides a comprehensive review of the management of women with HBV infection prior to conception, throughout each stage of pregnancy and postpartum, as well as recommendations and clinical approaches for the follow-up of children born to infected mothers, based on available evidence in the literature and recommendations from international experts. Prevention of perinatal transmission is an important component of global efforts to reduce the burden of chronic HBV since vertical transmission is responsible for most of the chronic infection worldwide. PMID:26475631

  2. ProSAT+: visualizing sequence annotations on 3D structure.

    PubMed

    Stank, Antonia; Richter, Stefan; Wade, Rebecca C

    2016-08-01

    PRO: tein S: tructure A: nnotation T: ool-plus (ProSAT(+)) is a new web server for mapping protein sequence annotations onto a protein structure and visualizing them simultaneously with the structure. ProSAT(+) incorporates many of the features of the preceding ProSAT and ProSAT2 tools but also provides new options for the visualization and sharing of protein annotations. Data are extracted from the UniProt KnowledgeBase, the RCSB PDB and the PDBe SIFTS resource, and visualization is performed using JSmol. User-defined sequence annotations can be added directly to the URL, thus enabling visualization and easy data sharing. ProSAT(+) is available at http://prosat.h-its.org. PMID:27284084

  3. Vaccination with a fusion DNA vaccine encoding hepatitis B surface antigen fused to the extracellular domain of CTLA4 enhances HBV-specific immune responses in mice: implication of its potential use as a therapeutic vaccine.

    PubMed

    Zhou, Cheng; Peng, Guoping; Jin, Xiaoli; Tang, Jie; Chen, Zhi

    2010-11-01

    Fusion of specific antigens to extracellular domain of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA4) represents a promising approach to increase the immunogenicity of DNA vaccines. We evaluated this interesting approach for its enhancement on HBV-specific immune responses and its antiviral effects in HBV transgenic mice. A fusion plasmid encoding the extracellular domain of CTLA4 linked with HBsAg was constructed. Mice were immunized by this fusion plasmid. Vaccination with the CTLA4-fused DNA not only induced much higher level of anti-HBs antibody, but also increased HBsAg-specific CD8+ response as well as CTL response in BALB/c mice. Furthermore, both Th1 and Th2 responses were augmented. In HBV transgenic mice, the levels of circulating HBsAg and HBV DNA replication were down-regulated by induction of higher anti-HBs antibody and HBsAg-specific CD8+ response after vaccination with the fusion plasmid. Thus, the CTLA4-fused DNA vaccine led to breakdown of immune tolerance to viral infection in HBV transgenic mice, which might be used as a therapeutic vaccine in HBV infection. PMID:20692873

  4. Pro-Anorexia and Anti-Pro-Anorexia Videos on YouTube: Sentiment Analysis of User Responses

    PubMed Central

    Garcia, David; Sirola, Anu; Näsi, Matti; Kaakinen, Markus; Keipi, Teo; Räsänen, Pekka

    2015-01-01

    Background Pro-anorexia communities exist online and encourage harmful weight loss and weight control practices, often through emotional content that enforces social ties within these communities. User-generated responses to videos that directly oppose pro-anorexia communities have not yet been researched in depth. Objective The aim was to study emotional reactions to pro-anorexia and anti-pro-anorexia online content on YouTube using sentiment analysis. Methods Using the 50 most popular YouTube pro-anorexia and anti-pro-anorexia user channels as a starting point, we gathered data on users, their videos, and their commentators. A total of 395 anorexia videos and 12,161 comments were analyzed using positive and negative sentiments and ratings submitted by the viewers of the videos. The emotional information was automatically extracted with an automatic sentiment detection tool whose reliability was tested with human coders. Ordinary least squares regression models were used to estimate the strength of sentiments. The models controlled for the number of video views and comments, number of months the video had been on YouTube, duration of the video, uploader’s activity as a video commentator, and uploader’s physical location by country. Results The 395 videos had more than 6 million views and comments by almost 8000 users. Anti-pro-anorexia video comments expressed more positive sentiments on a scale of 1 to 5 (adjusted prediction [AP] 2.15, 95% CI 2.11-2.19) than did those of pro-anorexia videos (AP 2.02, 95% CI 1.98-2.06). Anti-pro-anorexia videos also received more likes (AP 181.02, 95% CI 155.19-206.85) than pro-anorexia videos (AP 31.22, 95% CI 31.22-37.81). Negative sentiments and video dislikes were equally distributed in responses to both pro-anorexia and anti-pro-anorexia videos. Conclusions Despite pro-anorexia content being widespread on YouTube, videos promoting help for anorexia and opposing the pro-anorexia community were more popular, gaining more

  5. Association of Mutations in the Basal Core Promoter and Pre-core Regions of the Hepatitis B Viral Genome and Longitudinal Changes in HBV Level in HBeAg Negative Individuals: Results From a Cohort Study in Northern Iran

    PubMed Central

    Besharat, Sima; Poustchi, Hossein; Mohamadkhani, Ashraf; Katoonizadeh, Aezam; Moradi, Abdolvahab; Roshandel, Gholamreza; Freedman, Neal David; Malekzadeh, Reza

    2015-01-01

    Background: Although certain HBV mutations are known to affect the expression of Hepatitis e antigen, their association with HBV viral level or clinical outcomes is less clear. Objectives: We evaluated associations between different mutations in the Basal Core promoter (BCP) and Pre-core (PC) regions of HBV genome and subsequent changes in HBV viral DNA level over seven years in a population of untreated HBeAg negative chronic hepatitis B (CHB) participants in Northeast of Iran. Materials and Methods: Participants in the current study were drawn from the Golestan Hepatitis B Cohort Study (GHBCS), a cohort of approximately 2590 HBsAg positive subjects (living in Gonbad city) embedded in the Golestan Cohort Study (GCS). At baseline, HBsAg was measured in all participants and revealed 2590 HBsAg positive cases. We randomly selected 304 participants who their blood sample were taken at both baseline and seven years later in follow-up and had not been treated for HBV during this time. HBV viral load were assessed at baseline and at year 7. The BCP and PC regions of the HBV DNA, at baseline, were amplified via hemi-nested PCR and sequenced by cycle sequencing. At year 7, liver stiffness was assessed by fibroscan; also, other parameters of liver disease were assessed following standard clinical protocols. Associations were assessed via tabulation, chi-square, t-tests and logistic regression. P values < 0.05 were considered statistically significant and all tests were two-sided. Results: Among 304 HBsAg positive participants, 99 had detectable HBV DNA at study baseline. Of these, 61.6% had PC mutations (48.5% A1896 and 25.2% G1899). In contrast to other mutations, A1896 was associated with a higher proportion of detectable HBV DNA at year 7 (39.6%) compared to patients with the wild type (13.7%) (OR: 4.36, CI95% = 1.63-11.70; P Value = 0.002). Although participants with the A1896 mutation had higher year-7 HBV viral load than participants with G1896 (2.30 ± 1.66 IU/mL vs

  6. Pro-sociality and strategic reasoning in economic decisions

    PubMed Central

    Arruñada, Benito; Casari, Marco; Pancotto, Francesca

    2015-01-01

    We study the relationship between pro-social preferences and strategic reasoning. These aspects are typically studied separately but little is known about their joint distribution. In an experiment, for each participant we elicit individual concerns toward pro-sociality—inequality aversion and efficiency—as well as the number of steps of reasoning through a guessing game. We report that self-regarding and pro-social participants exhibit similar levels of strategic reasoning, which supports the view that pro-sociality and strategic reasoning can be studied independently. PMID:26074799

  7. InterPro, progress and status in 2005.

    PubMed

    Mulder, Nicola J; Apweiler, Rolf; Attwood, Teresa K; Bairoch, Amos; Bateman, Alex; Binns, David; Bradley, Paul; Bork, Peer; Bucher, Phillip; Cerutti, Lorenzo; Copley, Richard; Courcelle, Emmanuel; Das, Ujjwal; Durbin, Richard; Fleischmann, Wolfgang; Gough, Julian; Haft, Daniel; Harte, Nicola; Hulo, Nicolas; Kahn, Daniel; Kanapin, Alexander; Krestyaninova, Maria; Lonsdale, David; Lopez, Rodrigo; Letunic, Ivica; Madera, Martin; Maslen, John; McDowall, Jennifer; Mitchell, Alex; Nikolskaya, Anastasia N; Orchard, Sandra; Pagni, Marco; Ponting, Chris P; Quevillon, Emmanuel; Selengut, Jeremy; Sigrist, Christian J A; Silventoinen, Ville; Studholme, David J; Vaughan, Robert; Wu, Cathy H

    2005-01-01

    InterPro, an integrated documentation resource of protein families, domains and functional sites, was created to integrate the major protein signature databases. Currently, it includes PROSITE, Pfam, PRINTS, ProDom, SMART, TIGRFAMs, PIRSF and SUPERFAMILY. Signatures are manually integrated into InterPro entries that are curated to provide biological and functional information. Annotation is provided in an abstract, Gene Ontology mapping and links to specialized databases. New features of InterPro include extended protein match views, taxonomic range information and protein 3D structure data. One of the new match views is the InterPro Domain Architecture view, which shows the domain composition of protein matches. Two new entry types were introduced to better describe InterPro entries: these are active site and binding site. PIRSF and the structure-based SUPERFAMILY are the latest member databases to join InterPro, and CATH and PANTHER are soon to be integrated. InterPro release 8.0 contains 11 007 entries, representing 2573 domains, 8166 families, 201 repeats, 26 active sites, 21 binding sites and 20 post-translational modification sites. InterPro covers over 78% of all proteins in the Swiss-Prot and TrEMBL components of UniProt. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). PMID:15608177

  8. InterPro, progress and status in 2005

    PubMed Central

    Mulder, Nicola J.; Apweiler, Rolf; Attwood, Teresa K.; Bairoch, Amos; Bateman, Alex; Binns, David; Bradley, Paul; Bork, Peer; Bucher, Phillip; Cerutti, Lorenzo; Copley, Richard; Courcelle, Emmanuel; Das, Ujjwal; Durbin, Richard; Fleischmann, Wolfgang; Gough, Julian; Haft, Daniel; Harte, Nicola; Hulo, Nicolas; Kahn, Daniel; Kanapin, Alexander; Krestyaninova, Maria; Lonsdale, David; Lopez, Rodrigo; Letunic, Ivica; Madera, Martin; Maslen, John; McDowall, Jennifer; Mitchell, Alex; Nikolskaya, Anastasia N.; Orchard, Sandra; Pagni, Marco; Ponting, Chris P.; Quevillon, Emmanuel; Selengut, Jeremy; Sigrist, Christian J. A.; Silventoinen, Ville; Studholme, David J.; Vaughan, Robert; Wu, Cathy H.

    2005-01-01

    InterPro, an integrated documentation resource of protein families, domains and functional sites, was created to integrate the major protein signature databases. Currently, it includes PROSITE, Pfam, PRINTS, ProDom, SMART, TIGRFAMs, PIRSF and SUPERFAMILY. Signatures are manually integrated into InterPro entries that are curated to provide biological and functional information. Annotation is provided in an abstract, Gene Ontology mapping and links to specialized databases. New features of InterPro include extended protein match views, taxonomic range information and protein 3D structure data. One of the new match views is the InterPro Domain Architecture view, which shows the domain composition of protein matches. Two new entry types were introduced to better describe InterPro entries: these are active site and binding site. PIRSF and the structure-based SUPERFAMILY are the latest member databases to join InterPro, and CATH and PANTHER are soon to be integrated. InterPro release 8.0 contains 11 007 entries, representing 2573 domains, 8166 families, 201 repeats, 26 active sites, 21 binding sites and 20 post-translational modification sites. InterPro covers over 78% of all proteins in the Swiss-Prot and TrEMBL components of UniProt. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). PMID:15608177

  9. Pro-sociality and strategic reasoning in economic decisions.

    PubMed

    Arruñada, Benito; Casari, Marco; Pancotto, Francesca

    2015-01-01

    We study the relationship between pro-social preferences and strategic reasoning. These aspects are typically studied separately but little is known about their joint distribution. In an experiment, for each participant we elicit individual concerns toward pro-sociality-inequality aversion and efficiency-as well as the number of steps of reasoning through a guessing game. We report that self-regarding and pro-social participants exhibit similar levels of strategic reasoning, which supports the view that pro-sociality and strategic reasoning can be studied independently. PMID:26074799

  10. Development of cost-effective real-time PCR test: to detect a wide range of HBV DNA concentrations in the western amazon region of Brazil

    PubMed Central

    2014-01-01

    Background Currently there is a significant risk of infection with hepatitis B virus (HBV) during blood transfusion in high epidemic area. This is due to the pre-seroconversion window period, immunovariant viral strains and the presence of occult HBV infection (OBI). The aim of this study was to develop an in-house real-time PCR-based method, which was both ultra-sensitive and efficient offering an alternative method for nucleic acid testing (NAT). Methods A precore fragment with 109 bp was cloned and serial diluted to standard curve construction. The calibration of the HBV - DNA values was performed against OptiQuant® HBV-DNA Quantification Panel, Acrometrix Europe B.V.). Results From our in-house plasmid we prepared serial dilutions ranging from 2 × 103 – 2 × 109 copies/ml. The threshold was adjusted automatically during analysis and the data collected were analyzed by linear regression (r2 = 0.99). The limit of detection for the assay with pHBVRO standards was 2000/ml in a total reaction volume of 30 μl. We found a strong correlation between the two methods (r2 = 0.9965 and p < 0.0001). The regression line give us the following equation: Log 10 (IU/mL) = 0.9038Log 10 (copies/mL) − 1.0643, suggesting that 1 IU/mL = 15 copies/mL. Conclusions Therefore, we can affirm that the qHBVRO PCR can detect HBV DNA in individuals with hepatitis B at any stage of the disease showing high capacity for NAT screening in hepatitis b donors. This results of sensitivity could provide an advance for automation in blood banks and increasing safety of patients who receive blood transfusions. PMID:24472141

  11. IL-10-producing regulatory B-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection.

    PubMed

    Liu, Yun; Cheng, Li-Sha; Wu, Sheng-di; Wang, Si-Qi; Li, Lei; She, Wei-Min; Li, Jing; Wang, Ji-Yao; Jiang, Wei

    2016-06-01

    Non-specific immune responses to antigens have been demonstrated as being enhanced during chronic hepatitis B virus (HBV) infection. Here, we evaluated the role of interleukin-10 (IL-10)-producing regulatory B-cells (Bregs) in the pathogenesis of HBV-related liver fibrosis (HBV-LF) and assessed their immunoregulatory effects. Sixty-seven patients diagnosed with chronic hepatitis B (CHB) were enrolled in this study. Numbers and frequencies of peripheral B-cells (memory CD19(+)CD24(hi)CD27(+) cells, immature/transitional CD19(+)CD24(hi)CD38(hi) cells, mature CD19(+)CD24(int)CD38(int) cells) were tested and analysed. Flow cytometry-sorted CD4(+)T cells were cultured with autologous Bregs to elucidate the effects of Bregs on CD4(+)T cells, including effector T and regulatory T-cells (Tregs). The potential immunoregulatory mechanism of Bregs was also investigated. The numbers of total B-cells and Bregs were enriched in CHB patients. The frequency of Bregs was negatively correlated with elevated alanine aminotransferase (ALT) and histological inflammation grades (G), but positively correlated with advanced histological fibrosis stages (S) and enhanced HBV replication. The phenotype of Bregs was predominantly characterized as CD19(+)CD24(hi)CD38(hi) In co-culture with Bregs, CD4(+)CD25(-)T cells from CHB patients produced less interferon-γ (IFN-γ) and IL-17 but more IL-4 than CD4(+)CD25(-)T cells alone, whereas their conversions into Tregs and IL-10(+)T cells were enhanced. In addition, Breg depletion in CHB samples dramatically decreased Treg numbers and expression of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4), IL-10 and transforming growth factor-β (TGF-β). Moreover, the observed regulatory effect was partly dependent on IL-10 release and cell-to-cell contact. Elevated Bregs can suppress effector T but enhance Treg functions, which might influence immune tolerance in chronic HBV infection. PMID:26980345

  12. Studies on Viral Disinfection: An Evaluation of Moist Heat Disinfection for HBV by Using A0 Concept Defined in ISO 15883-Washer-Disinfectors.

    PubMed

    Uetera, Yushi; Kawamura, Kunio; Kobayashi, Hiroyoshi; Saito, Yuhei; Yasuhara, Hiroshi; Saito, Ryoichi

    2010-01-01

    International Organization for Standardization (ISO) 15883 for washer-disinfectors has introduced the A(0) concept to allow comparison of the lethality of moist heat processes. The A(0) value is the equivalent disinfection time in seconds at 80 °C calculated on the basis of microbial killing kinetics when the disinfection temperature is over 65 °C. Hepatitis B virus (HBV), transmissible only to humans and chimpanzees, is an important heat-resistant, blood-borne pathogen. Therefore, it is mandatory to disinfect HBV thoroughly in the washer-disinfectors employed for surgical instruments. Additionally, it has become extremely difficult to use chimpanzees as experimental models or to perform human volunteer studies. Therefore, it is considered worthwhile to re-evaluate the reported data on the moist heat disinfection of HBV using the A(0) value. In the voluntary active immunization to humans in 1973, HBV serum (infectivity titer: 10(6.5) CID(50)/mL) underwent moist heat disinfection at 98 °C for 1 min in a flask over an electric burner (conservatively estimated A(0) value: 3786). Then, 0.1 mL was inoculated to each of 29 volunteers. No one revealed evidence of infection clinically or in the laboratory tests available at the time. In 1979, a more sensitive test appeared and revealed three sub-clinically infected volunteers. In the 1980s, there were two chimpanzee experimental models using HBV serum (infectivity titer: 10(5) CID(50)/mL). In one model, the serum underwent moist heat disinfection at 98 °C for 2 min in a thermostat bath (conservatively estimated A(0) value: 7571). One milliliter was inoculated to each of two chimpanzees, and both of them revealed no evidence of infection. In another model, the serum underwent moist heat disinfection using two conditions in a thermostat bath, respectively: at 103 °C for 90 s (A(0) value: 24865) and at 65 °C for 10 h (A(0) value: 1138). Ten milliliters of each sample were mixed. Then, the mixture was inoculated to each

  13. French Pro/Am collaborations in exoplanet

    NASA Astrophysics Data System (ADS)

    Santerne, A.; Moutou, C.; Vanhuysse, M.; Bouchy, F.; Buil, C.; Cochard, F.; Thizy, O.; Martinez, P.; Desnoux, V.; Pujol, M.; Colas, F.

    2011-10-01

    Amateur astronomers have access to huge telescope time and can reach photometric precision up to a few mmag as well as radial velocity precision up to ˜ 50m.s-1 on brightest stars. We will first present some results of french amateur astronomers in transit photometry and radial velocity and then, we will present an over-view of all the collaborations which can be done between professional and amateur astronomers in the competitive exoplanet domain, and especially the current collaboration between french Pro & Am astronomers which was used in publication in A&A. Finally, we will present a new internet wiki page which goal is to develop such collaboration in different countries.

  14. Overrepresentation of IL-10-Expressing B Cells Suppresses Cytotoxic CD4+ T Cell Activity in HBV-Induced Hepatocellular Carcinoma

    PubMed Central

    Tan, Hongwu; Zhu, Zun-Qiang; Zhang, Zhang-Yun; Zhao, Ludong

    2016-01-01

    Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis and low five-year survival rate. A strong and effective CD4+ T cell-mediated cytotoxicity was associated with better survival and low recurrence rate in HCC, but the regulatory mechanism that controls CD4+ T cell cytotoxicity in HCC patients is not fully examined. Given that IL-10-expressing B cells could suppress the inflammation of cytotoxic CD8+ T cells, T helper 1 (Th1) cells and Th17 cells, while promoting regulatory T (Treg) cell differentiation, we examined the role of IL-10-expressing B cells in HBV-related HCC patients. We found that compared to healthy controls, HCC patients exhibited significantly higher frequencies of IL-10-expressing B cells, which were negatively correlated with the frequencies of granzyme A, granzyme B, and perforin expressing CD4+ T cells. Surface molecule Tim-1 was preferentially expressed on IL-10-expressing B cells. Therefore, we separated total B cells into Tim-1+ and Tim-1- B cells. CD4+ T cells incubated with Tim-1+ B cells exhibited significantly reduced levels of granzyme A, granzyme B and perforin expression, compared to the CD4+ T cells incubated with Tim-1- B cells. Antagonizing IL-10 in culture rescued CD4+ T cell cytotoxicity. Compared to that in peripheral blood, the level of IL-10-expressing B cells were further upregulated in resected tumor, while the level of CD4+ cytotoxic T cells was downregulated. The negative correlations between IL-10-expressing B cells and CD4+ cytotoxic T cells were also observed in tumor-infiltrating cells. Together, our data revealed an additional antitumor mechanism mediated by IL-10-expressing B cells. PMID:27136203

  15. Overrepresentation of IL-10-Expressing B Cells Suppresses Cytotoxic CD4+ T Cell Activity in HBV-Induced Hepatocellular Carcinoma.

    PubMed

    Xue, Hongwei; Lin, Fuhuang; Tan, Hongwu; Zhu, Zun-Qiang; Zhang, Zhang-Yun; Zhao, Ludong

    2016-01-01

    Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis and low five-year survival rate. A strong and effective CD4+ T cell-mediated cytotoxicity was associated with better survival and low recurrence rate in HCC, but the regulatory mechanism that controls CD4+ T cell cytotoxicity in HCC patients is not fully examined. Given that IL-10-expressing B cells could suppress the inflammation of cytotoxic CD8+ T cells, T helper 1 (Th1) cells and Th17 cells, while promoting regulatory T (Treg) cell differentiation, we examined the role of IL-10-expressing B cells in HBV-related HCC patients. We found that compared to healthy controls, HCC patients exhibited significantly higher frequencies of IL-10-expressing B cells, which were negatively correlated with the frequencies of granzyme A, granzyme B, and perforin expressing CD4+ T cells. Surface molecule Tim-1 was preferentially expressed on IL-10-expressing B cells. Therefore, we separated total B cells into Tim-1+ and Tim-1- B cells. CD4+ T cells incubated with Tim-1+ B cells exhibited significantly reduced levels of granzyme A, granzyme B and perforin expression, compared to the CD4+ T cells incubated with Tim-1- B cells. Antagonizing IL-10 in culture rescued CD4+ T cell cytotoxicity. Compared to that in peripheral blood, the level of IL-10-expressing B cells were further upregulated in resected tumor, while the level of CD4+ cytotoxic T cells was downregulated. The negative correlations between IL-10-expressing B cells and CD4+ cytotoxic T cells were also observed in tumor-infiltrating cells. Together, our data revealed an additional antitumor mechanism mediated by IL-10-expressing B cells. PMID:27136203

  16. 25 CFR 273.32 - Pro rata requirement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Pro rata requirement. 273.32 Section 273.32 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR INDIAN SELF-DETERMINATION AND EDUCATION ASSISTANCE ACT PROGRAM EDUCATION CONTRACTS UNDER JOHNSON-O'MALLEY ACT Funding Provisions § 273.32 Pro...

  17. Ethical Dilemmas of Providing Pro Bono Art Therapy

    ERIC Educational Resources Information Center

    Moon, Bruce L.

    2011-01-01

    This viewpoint addresses ethical questions regarding the provision of art therapy as a pro bono service, a term from Latin roots that mean "for the public good." Approaches to ethical reasoning are discussed using the case of pro bono art therapy in a residential treatment program for adolescents.

  18. Body composition of transgenic pigs expressing the myostatin pro domain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous results have shown that male mice expressing a myostatin pro domain construct (MLC-Pro) have increased body weight, more total body lean mass, and lower percentage of total body fat. Founder transgenic (TG) pigs were generated by standard pronuclear microinjection techniques using the sam...

  19. 31 CFR 50.92 - Determination of pro rata share.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INSURANCE PROGRAM Cap on Annual Liability § 50.92 Determination of pro rata share. (a) Pro rata loss... providing property and casualty insurance under the Program if there were no cap on annual liability under... estimates that aggregate insured losses may exceed the cap on annual liability for a Program Year,...

  20. Peanuts & Crackerjacks: Economics of Pro Team Sports. Teacher's Guide.

    ERIC Educational Resources Information Center

    Federal Reserve Bank of Boston, MA.

    This teacher's guide presents instructional materials which examine issues in professional sports for students in high school economics and social studies classes. The issues include how the pro sports market evolved; how leagues gained market power; why athletes earn as much as they do; what are the sources of pro sports revenues; why tickets…

  1. 25 CFR 273.32 - Pro rata requirement.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Pro rata requirement. 273.32 Section 273.32 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR INDIAN SELF-DETERMINATION AND EDUCATION ASSISTANCE ACT PROGRAM EDUCATION CONTRACTS UNDER JOHNSON-O'MALLEY ACT Funding Provisions § 273.32 Pro...

  2. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  3. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  4. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  5. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  6. 48 CFR 352.237-70 - Pro-Children Act.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Pro-Children Act. 352.237...-Children Act. As prescribed in 337.103-70(a), the Contracting Officer shall insert the following clause: Pro-Children Act (January 2006) (a) Public Law 103-227, Title X, Part C, also known as the...

  7. Pro-Market Educational Governance: Is Argentina a Black Swan?

    ERIC Educational Resources Information Center

    Beech, Jason; Barrenechea, Ignacio

    2011-01-01

    In this article we explore ways in which pro-market discourses have been interpreted in policy initiatives in Argentina since the 1970s. Our argument is that even though pro-market discourses have guided reforms in many aspects of public policies in Argentina, the arena of education has overall been resistant to taking them up. The first part of…

  8. Pro-Cite: A Tool for Creating and Updating Bibliographies.

    ERIC Educational Resources Information Center

    Aluri, Rao; Bosch, Steve

    1987-01-01

    Describes the Pro-Cite database management system and its uses in searching RLIN, OCLC, DIALOG, BRS, etc.; downloading results on a floppy or hard disk; converting downloaded records into Pro-Cite databases; and editing, selecting, indexing, and printing out the selected records in a variety of bibliographic styles. (DMM)

  9. Intracerebroventricular infusion of the (Pro)renin receptor antagonist PRO20 attenuates deoxycorticosterone acetate-salt-induced hypertension.

    PubMed

    Li, Wencheng; Sullivan, Michelle N; Zhang, Sheng; Worker, Caleb J; Xiong, Zhenggang; Speth, Robert C; Feng, Yumei

    2015-02-01

    We previously reported that binding of prorenin to the (pro)renin receptor (PRR) plays a major role in brain angiotensin II formation and the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Here, we designed and developed an antagonistic peptide, PRO20, to block prorenin binding to the PRR. Fluorescently labeled PRO20 bound to both mouse and human brain tissues with dissociation constants of 4.4 and 1.8 nmol/L, respectively. This binding was blocked by coincubation with prorenin and was diminished in brains of neuron-specific PRR-knockout mice, indicating specificity of PRO20 for PRR. In cultured human neuroblastoma cells, PRO20 blocked prorenin-induced calcium influx in a concentration- and AT(1) receptor-dependent manner. Intracerebroventricular infusion of PRO20 dose-dependently inhibited prorenin-induced hypertension in C57Bl6/J mice. Furthermore, acute intracerebroventricular infusion of PRO20 reduced blood pressure in both DOCA-salt and genetically hypertensive mice. Chronic intracerebroventricular infusion of PRO20 attenuated the development of hypertension and the increase in brain hypothalamic angiotensin II levels induced by DOCA-salt. In addition, chronic intracerebroventricular infusion of PRO20 improved autonomic function and spontaneous baroreflex sensitivity in mice treated with DOCA-salt. In summary, PRO20 binds to both mouse and human PRRs and decreases angiotensin II formation and hypertension induced by either prorenin or DOCA-salt. Our findings highlight the value of the novel PRR antagonist, PRO20, as a lead compound for a novel class of antihypertensive agents and as a research tool to establish the validity of brain PRR antagonism as a strategy for treating hypertension. PMID:25421983

  10. 20 CFR 416.1133 - What is a pro rata share of household operating expenses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false What is a pro rata share of household....1133 What is a pro rata share of household operating expenses. (a) General. If you pay your pro rata..., we value it under the rule in § 416.1140.) (b) How we determine a pro rata share. Your pro rata...

  11. Profiling the ‘Pro-environmental Individual’: A Personality Perspective

    PubMed Central

    Markowitz, Ezra M.; Goldberg, Lewis R.; Ashton, Michael C.; Lee, Kibeom

    2011-01-01

    There is considerable scientific interest in the psychological correlates of pro-environmental behaviors. Much research has focused on demographic and social-psychological characteristics of individuals who consistently perform such actions. Here, we report the results of two studies in which we explored relations between broad personality traits and pro-environmental actions. Using a wide variety of behavior and personality measures, we consistently found moderate positive relations between Openness to Experience and pro-environmental activities in both a community sample (Study 1: N = 778) and an undergraduate student sample (Study 2: N = 115). In Study 2 we showed that the effect of Openness on pro-environmental behaviors was fully mediated by individuals’ environmental attitudes and connection to nature. Our findings suggest that high levels of aesthetic appreciation, creativity, and inquisitiveness, but not personality traits associated with altruism, may have motivated the performance of pro-environmental actions among our respondents. Implications for intervention development are discussed. PMID:21241310

  12. Pro-resolving lipid mediators are leads for resolution physiology.

    PubMed

    Serhan, Charles N

    2014-06-01

    Advances in our understanding of the mechanisms that bring about the resolution of acute inflammation have uncovered a new genus of pro-resolving lipid mediators that include the lipoxin, resolvin, protectin and maresin families, collectively called specialized pro-resolving mediators. Synthetic versions of these mediators have potent bioactions when administered in vivo. In animal experiments, the mediators evoke anti-inflammatory and novel pro-resolving mechanisms, and enhance microbial clearance. Although they have been identified in inflammation resolution, specialized pro-resolving mediators are conserved structures that also function in host defence, pain, organ protection and tissue remodelling. This Review covers the mechanisms of specialized pro-resolving mediators and omega-3 essential fatty acid pathways that could help us to understand their physiological functions. PMID:24899309

  13. The Experience of Bulimic College Students Who Use "Pro-Ana/Pro-Mia" Web Sites: A Two-Phase Mixed-Method Study

    ERIC Educational Resources Information Center

    Davis, Blair J.

    2010-01-01

    Eating disorders (EDs) are a serious problem in the U.S. due to their rise in prevalence during the 20th century and high morbidity and mortality rates. A relatively new, controversial phenomenon, "pro-Ana" (pro-anorexia) and "pro-Mia" (pro-bulimia) Web sites, came to the public's attention around 2000. These sites are created by and for people…

  14. Test Reviews: Reynolds, C., & Voress, J. K. (2007). "Test of Memory and Learning: Second Edition." Austin, TX: PRO-ED

    ERIC Educational Resources Information Center

    Schmitt, Ara J.; Decker, Scott L.

    2009-01-01

    This article reviews the Test of Memory and Learning: Second Edition (TOMAL-2), published by PRO-ED, which constitutes a recent revision of the Test of Memory and Learning (TOMAL; Reynolds & Bigler, 1994). Advertised as the "single most comprehensive memory battery available for the entire age range of 5 years through 59 years of age", the TOMAL-2…

  15. Genomic Methylation Inhibits Expression of Hepatitis B Virus Envelope Protein in Transgenic Mice: A Non-Infectious Mouse Model to Study Silencing of HBV Surface Antigen Genes

    PubMed Central

    Graumann, Franziska; Churin, Yuri; Tschuschner, Annette; Reifenberg, Kurt; Glebe, Dieter; Roderfeld, Martin; Roeb, Elke

    2015-01-01

    Objective The Hepatitis B virus genome persists in the nucleus of virus infected hepatocytes where it serves as template for viral mRNA synthesis. Epigenetic modifications, including methylation of the CpG islands contribute to the regulation of viral gene expression. The present study investigates the effects of spontaneous age dependent loss of hepatitis B surface protein- (HBs) expression due to HBV-genome specific methylation as well as its proximate positive effects in HBs transgenic mice. Methods Liver and serum of HBs transgenic mice aged 5–33 weeks were analyzed by Western blot, immunohistochemistry, serum analysis, PCR, and qRT-PCR. Results From the third month of age hepatic loss of HBs was observed in 20% of transgenic mice. The size of HBs-free area and the relative number of animals with these effects increased with age and struck about 55% of animals aged 33 weeks. Loss of HBs-expression was strongly correlated with amelioration of serum parameters ALT and AST. In addition lower HBs-expression went on with decreased ER-stress. The loss of surface protein expression started on transcriptional level and appeared to be regulated epigenetically by DNA methylation. The amount of the HBs-expression correlated negatively with methylation of HBV DNA in the mouse genome. Conclusions Our data suggest that methylation of specific CpG sites controls gene expression even in HBs-transgenic mice with truncated HBV genome. More important, the loss of HBs expression and intracellular aggregation ameliorated cell stress and liver integrity. Thus, targeted modulation of HBs expression may offer new therapeutic approaches. Furthermore, HBs-transgenic mice depict a non-infectious mouse model to study one possible mechanism of HBs gene silencing by hypermethylation. PMID:26717563

  16. EGFR and SYNE2 are associated with p21 expression and SYNE2 variants predict post-operative clinical outcomes in HBV-related hepatocellular carcinoma

    PubMed Central

    Han, Chuangye; Liao, Xiwen; Qin, Wei; Yu, Long; Liu, Xiaoguang; Chen, Gang; Liu, Zhengtao; Lu, Sicong; Chen, Zhiwei; Su, Hao; Zhu, Guangzhi; Lu, Zili; Liu, Zhiming; Qin, Xue; Gui, Ying; Mo, Zengnan; Li, Lequn; Peng, Tao

    2016-01-01

    This study was to explore the association between gene variants and p21 expression and investigate the TP53-independent p21 regulation in hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients from Guangxi by genome-wide association study. 426 HBV-related HCC patients were enrolled. Results showed that, after quality control, a total of 21,643 SNPs were identified in 107 p21 positive and 298 p21 negative patients. The variants of epidermal growth factor receptor (EGFR; rs2227983 and rs6950826) and spectrin repeat containing, nuclear envelope 2 (SYNE2; rs8010699, rs4027405 and rs1890908) were associated with p21 expression. Moreover the haplotype block (rs2227983 and rs6950826, r2 = 0.378) in EGFR and the haplotype block in SYNE2 (rs8010699 was in strong LD with rs4027405 and rs1890908 (r2 = 0.91 and 0.70, respectively)) were identified, and the haplotype A-G of EGFR and haplotype G-A-A of SYNE2 were significantly associated with p21 expression (P < 0.01). rs4027405 and rs1890908 were significantly associated with overall survival, and patients with AG/GG genotypes of SYNE2 gene had a worse overall survival (P = 0.001, P = 0.002). Our findings indicate that variants of EGFR and SYNE2 play an important role in p21 regulation and are associated with the clinical outcome of HBV-related HCC in a TP53-indenpdent manner. PMID:27502069

  17. EGFR and SYNE2 are associated with p21 expression and SYNE2 variants predict post-operative clinical outcomes in HBV-related hepatocellular carcinoma.

    PubMed

    Han, Chuangye; Liao, Xiwen; Qin, Wei; Yu, Long; Liu, Xiaoguang; Chen, Gang; Liu, Zhengtao; Lu, Sicong; Chen, Zhiwei; Su, Hao; Zhu, Guangzhi; Lu, Zili; Liu, Zhiming; Qin, Xue; Gui, Ying; Mo, Zengnan; Li, Lequn; Peng, Tao

    2016-01-01

    This study was to explore the association between gene variants and p21 expression and investigate the TP53-independent p21 regulation in hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients from Guangxi by genome-wide association study. 426 HBV-related HCC patients were enrolled. Results showed that, after quality control, a total of 21,643 SNPs were identified in 107 p21 positive and 298 p21 negative patients. The variants of epidermal growth factor receptor (EGFR; rs2227983 and rs6950826) and spectrin repeat containing, nuclear envelope 2 (SYNE2; rs8010699, rs4027405 and rs1890908) were associated with p21 expression. Moreover the haplotype block (rs2227983 and rs6950826, r(2) = 0.378) in EGFR and the haplotype block in SYNE2 (rs8010699 was in strong LD with rs4027405 and rs1890908 (r(2) = 0.91 and 0.70, respectively)) were identified, and the haplotype A-G of EGFR and haplotype G-A-A of SYNE2 were significantly associated with p21 expression (P < 0.01). rs4027405 and rs1890908 were significantly associated with overall survival, and patients with AG/GG genotypes of SYNE2 gene had a worse overall survival (P = 0.001, P = 0.002). Our findings indicate that variants of EGFR and SYNE2 play an important role in p21 regulation and are associated with the clinical outcome of HBV-related HCC in a TP53-indenpdent manner. PMID:27502069

  18. Hepatitis B virus nuclear export elements: RNA stem-loop α and β, key parts of the HBV post-transcriptional regulatory element.

    PubMed

    Lim, Chun Shen; Brown, Chris M

    2016-09-01

    Many viruses contain RNA elements that modulate splicing and/or promote nuclear export of their RNAs. The RNAs of the major human pathogen, hepatitis B virus (HBV) contain a large (~600 bases) composite cis-acting 'post-transcriptional regulatory element' (PRE). This element promotes expression from these naturally intronless transcripts. Indeed, the related woodchuck hepadnavirus PRE (WPRE) is used to enhance expression in gene therapy and other expression vectors. These PRE are likely to act through a combination of mechanisms, including promotion of RNA nuclear export. Functional components of both the HBV PRE and WPRE are 2 conserved RNA cis-acting stem-loop (SL) structures, SLα and SLβ. They are within the coding regions of polymerase (P) gene, and both P and X genes, respectively. Based on previous studies using mutagenesis and/or nuclear magnetic resonance (NMR), here we propose 2 covariance models for SLα and SLβ. The model for the 30-nucleotide SLα contains a G-bulge and a CNGG(U) apical loop of which the first and the fourth loop residues form a CG pair and the fifth loop residue is bulged out, as observed in the NMR structure. The model for the 23-nucleotide SLβ contains a 7-base-pair stem and a 9-nucleotide loop. Comparison of the models with other RNA structural elements, as well as similarity searches of human transcriptome and viral genomes demonstrate that SLα and SLβ are specific to HBV transcripts. However, they are well conserved among the hepadnaviruses of non-human primates, the woodchuck and ground squirrel. PMID:27031749

  19. HIV-1, HBV, HCV, HTLV, HPV-16/18, and Treponema pallidum Infections in a Sample of Brazilian Men Who Have Sex with Men

    PubMed Central

    Soares, Caroline C.; Georg, Ingebourg; Lampe, Elisabeth; Lewis, Lia; Morgado, Mariza G.; Nicol, Alcina F.; Pinho, Adriana A.; Salles, Regina C. S.; Teixeira, Sylvia L. M.; Vicente, Ana Carolina P.; Viscidi, Raphael P.; Gomes, Selma A.

    2014-01-01

    Background Men who have sex with men (MSM) are more vulnerable to blood-borne infections and/or sexually-transmitted infections (STI). This study was conducted to estimate the prevalences of mono and co-infections of HIV-1 and other blood-borne/STIs in a sample of MSM in Campinas, Brazil. Methods Responding Driven Sampling (RDS) was used for recruitment of MSM. Serum samples collected from 558 MSM were analyzed for the presence of serological markers for HIV-1, HBV, HCV, HTLV, HPV-16/18, and T. pallidum infections. Results The highest prevalences of infection in serum samples were found for HPV-16 and 18 (31.9% and 20.3%, respectively). Approximately 8% of the study population showed infection with HIV-1, and within that group, 27.5% had recently become infected with HIV-1. HBV infection and syphilis were detected in 11.4% and 10% of the study population, respectively, and the rates of HTLV and HCV infection were 1.5% and 1%, respectively. With the exception of HTLV, all other studied infections were usually found as co-infections rather then mono-infections. The rates of co-infection for HCV, HPV-18, and HIV-1 were the highest among the studied infections (100%, 83%, and 85%, respectively). Interestingly, HTLV infection was usually found as a mono-infection in the study group, whereas HCV was found only as a co-infection. Conclusions The present findings highlight the need to educate the MSM population concerning their risk for STIs infections and methods of prevention. Campaigns to encourage vaccination against HBV and HPV could decrease the rates of these infections in MSM. PMID:25083768

  20. A multiphase model of the dynamics of HBV infection in HBeAg-negative patients during pegylated interferon-alpha2a, lamivudine and combination therapy.

    PubMed

    Colombatto, Piero; Civitano, Luigi; Bizzarri, Ranieri; Oliveri, Filippo; Choudhury, Somesh; Gieschke, Ronald; Bonino, Ferruccio; Brunetto, Maurizia R

    2006-01-01

    Using a multiphase bio-mathematical model, we studied the dynamics of hepatitis B virus (HBV) infection in 72 HBeAg-negative patients who received 48 weeks of either lamivudine (3TC; 25 patients); pegylated interferon-alpha2a (peg-IFN-alpha2a) 180 mg weekly plus 3TC (23 patients), or peg-IFN-alpha2a 180 mg weekly plus placebo (24 patients). During the first month of therapy most of the 3TC -/+ peg-IFN-alpha2a treated patients showed a multiphase decay of viral load: during the first two phases, where we hypothesized a direct inhibition of virus production, the mean viral production per infected cell was reduced by 2.22 log10 and 2.36 log10, respectively. At variance, peg-IFN-alpha2a treated patients had a biphasic profile: the first phase HBV DNA decline was slower than that observed in 3TC patients (mean HBV DNA t(1/2) = 1.6 +/- 1.1 days and 9.5 +/- 3.0 h, respectively) and the direct antiviral effect reduced virus production by 1.14 log10. From day 14 onwards (third or second phase according to multi- or biphasic patterns), HBV DNA declined mainly because of the infected hepatocyte clearance that slowed down in approximately 50% of the patients from day 35, possibly because of a negative feedback on the immune system activity. Computing the number of infected cells at the end of therapy we found that peg-IFN-alpha2a and 3TC monotherapy determined a similar reduction of infected hepatocytes (mean: -3.3 log10), whereas there was a greater reduction in combination therapy patients (-5.0 versus -3.3 log10, P = 0.039). In conclusion, peg-IFN-alpha2a, in spite of having direct antiviral activity lower than that of 3TC, achieved a comparable reduction of infected hepatocytes, possibly because of a higher infected cell clearance rate. PMID:16640101

  1. Upregulation of miRNA-130a Represents Good Prognosis in Patients With HBV-Related Acute-on-Chronic Liver Failure: A Prospective Study.

    PubMed

    Zheng, Qing-Fen; Zhang, Jing-Yun; Wu, Ju-Shan; Zhang, Ying; Liu, Mei; Bai, Li; Zhang, Jin-Yan; Zhao, Jing; Chen, Yu; Duan, Zhong-Ping; Zheng, Su-Jun

    2016-02-01

    Prompt and accurate prediction of the outcome is the key to make correct medical decision and to reduce the mortality in patients with HBV-related acute-on-chronic liver failure (ACLF). Increasing evidence have certified that small, noncoding microRNAs (miRNAs) play critically regulatory roles in the pathogenesis of liver diseases. However, it remains unclear whether and how miRNAs involve in the prognosis of ACLF.Microarray analysis was performed to characterize the miRNA expression profiles in liver tissues from 1 HBV-related ACLF patient and 1 matched healthy control. Nine miRNAs with at least 5 folds difference between these 2 persons were picked out. The present prospective study involving 39 HBV-related ACLF patients including 20 recovered and 19 nonrecovered patients, which include death (n = 9) and liver transplantation (n = 10). The serum expression of these miRNAs detected by quantitative real-time Polymerase Chain Reaction (qRT-RCR) was then compared between the 2 groups. Moreover, the correlation between the serum miRNAs and the prognostic indexes for ACLF was analyzed.The result of microarray analysis showed 9 miRNAs had different expression in liver tissues of ACLF patient compared with healthy control (upregulated: miRNA-130a, -21, -143, and -200a; downregulated: miRNA-486-5p, -192, -148a, -122, and -194). Unlike the expression profiles in liver tissue, 8 serum miRNAs except miRNA-194 were markedly upregulated in ACLF patients (P < 0.05). Remarkably, the serum expression of miRNA-130a and miRNA-486-5p was higher in recovered than nonrecovered ACLF patients (P < 0.05). Especially, the serum miRNA-130a was negatively correlated with international normalized ratio, prothrombin time, Model for End-Stage Liver Disease score, and positively correlated with prothrombin time activity. The AUC for recovered versus nonrecovered patients of miRNA-130a was 0.741 (P = 0.02).miRNA-130a might be a useful prognosis biomarker in patients with HBV

  2. Design, Synthesis, and Evaluation of Anti-HBV Activity of Hybrid Molecules of Entecavir and Adefovir: Exomethylene Acycloguanine Nucleosides and Their Monophosphate Derivatives.

    PubMed

    Imoto, Shuhei; Kohgo, Satoru; Tokuda, Ryoh; Kumamoto, Hiroki; Aoki, Manabu; Amano, Masayuki; Kuwata-Higashi, Nobuyo; Mitsuya, Hiroaki; Haraguchi, Kazuhiro

    2015-01-01

    Exomethylene acycloguanine nucleosides 4, 6 and its monophosphate derivatives 5, 7, and 8 have been synthesized. Mitsunobu-type coupling of 2-N-acetyl-6-O-diphenylcarbamoylguanine (11) with primary alcohols proceeded regioselectively to furnish the desired N(9)-substituted products in moderate yield. Evaluation of 4-8 for anti-HBV activity in HepG2 cells revealed that the phosphonate derivative 8 was found to exhibit moderated activity (EC50 value of 0.29 μM), but cytotoxicity (CC50 value of 39 μM) against the host cells was also observed. PMID:26167667

  3. P5CDH affects the pathways contributing to Pro synthesis after ProDH activation by biotic and abiotic stress conditions

    PubMed Central

    Rizzi, Yanina S.; Monteoliva, Mariela I.; Fabro, Georgina; Grosso, Carola L.; Laróvere, Laura E.; Alvarez, María E.

    2015-01-01

    Plants facing adverse conditions usually alter proline (Pro) metabolism, generating changes that help restore the cellular homeostasis. These organisms synthesize Pro from glutamate (Glu) or ornithine (Orn) by two-step reactions that share Δ1 pyrroline-5-carboxylate (P5C) as intermediate. In the catabolic process, Pro is converted back to Glu using a different pathway that involves Pro dehydrogenase (ProDH), P5C dehydrogenase (P5CDH), and P5C as intermediate. Little is known about the coordination of the catabolic and biosynthetic routes under stress. To address this issue, we analyzed how P5CDH affects the activation of Pro synthesis, in Arabidopsis tissues that increase ProDH activity by transient exposure to exogenous Pro, or infection with Pseudomonas syringae pv. tomato. Wild-type (Col-0) and p5cdh mutant plants subjected to these treatments were used to monitor the Pro, Glu, and Orn levels, as well as the expression of genes from Pro metabolism. Col-0 and p5cdh tissues consecutively activated ProDH and Pro biosynthetic genes under both conditions. However, they manifested a different coordination between these routes. When external Pro supply was interrupted, wild-type leaves degraded Pro to basal levels at which point Pro synthesis, mainly via Glu, became activated. Under the same condition, p5cdh leaves sustained ProDH induction without reducing the Pro content but rather increasing it, apparently by stimulating the Orn pathway. In response to pathogen infection, both genotypes showed similar trends. While Col-0 plants seemed to induce both Pro biosynthetic routes, p5cdh mutant plants may primarily activate the Orn route. Our study contributes to the functional characterization of P5CDH in biotic and abiotic stress conditions, by revealing its capacity to modulate the fate of P5C, and prevalence of Orn or Glu as Pro precursors in tissues that initially consumed Pro. PMID:26284090

  4. Pro-angiogenic properties of orosomucoid (ORM)

    SciTech Connect

    Irmak, Ster; Oliveira-Ferrer, Leticia; Erguen, Sueleyman; Tilki, Derya

    2009-11-01

    The acute phase protein orosomucoid (ORM), also known as alpha1-acid glycoprotein (AGP), is found to be increased in infection, inflammation and cancer. Recently, we demonstrated that ORM is produced by endothelial cells and detectable in urine samples of patients with bladder cancer. However, it was not clarified yet whether ORM plays a role in new vessel formation. To this aim we performed overexpression and gene silencing for ORM in human microvascular endothelial cells (HDMECs). ORM purified from human plasma was used individually or in combination with VEGF-A in endothelial tube formation, migration and proliferation assay. The in vivo effect of ORM in angiogenesis was studied using the chicken chorionallantois membrane (CAM) with subsequent counting of blood vessels on histological sections from the stimulated areas of CAM tissue. Our data show that ORM alone enhances migration but not proliferation of HDMECs. ORM alone does not induce endothelial tubes in vitro but simultaneous application of ORM with VEGF-A increases the number and the network of VEGF-A-induced endothelial tubes. Remarkably, ORM alone induces new vessel formation in vivo using CAM assay and supports the VEGF-A-induced new vessel formation in this assay. Taken together, our results let assume that ORM has pro-angiogenic properties and supports the angiogenic effect of VEGF-A. Thus, ORM seems to be involved in the regulation of angiogenesis.

  5. ProPortal: A Database for Prochlorococcus

    DOE Data Explorer

    Huang, Katherine [Chisholm lab, MIT

    Prochlorococcus is a marine cyanobacterium that numerically dominates the mid-latitude oceans, and is the smallest known oxygenic phototroph. All isolates described thus far can be assigned to either a tightly clustered high-light (HL) adapted clade, or a more divergent low-light (LL) adapted group. They are closely related to, but distinct from, marine Synechococcus. The genomes of 12 strains have been sequenced and they range in size from 1.6 to 2.6 Mbp. They represent diverse lineages, spanning the rRNA diversity (97 to 99.93% similarity) of cultured representatives of this group. Our analyses of these genomes inform our understanding of how adaptation occurs in the oceans along gradients of light, nutrients, and other environmental factors, providing essential context for interpreting rapidly expanding metagenomic datasets. [Copied from http://proportal.mit.edu/project/prochlorococcus/] ProPortal allows users to browse and search genome date for not only Prochlorococcus, but Cyanophage and Synechococcus. Microarray data, environmental cell concentration data, and metagenome information are also available.

  6. ProCon - PROteomics CONversion tool.

    PubMed

    Mayer, Gerhard; Stephan, Christian; Meyer, Helmut E; Kohl, Michael; Marcus, Katrin; Eisenacher, Martin

    2015-11-01

    With the growing amount of experimental data produced in proteomics experiments and the requirements/recommendations of journals in the proteomics field to publicly make available data described in papers, a need for long-term storage of proteomics data in public repositories arises. For such an upload one needs proteomics data in a standardized format. Therefore, it is desirable, that the proprietary vendor's software will integrate in the future such an export functionality using the standard formats for proteomics results defined by the HUPO-PSI group. Currently not all search engines and analysis tools support these standard formats. In the meantime there is a need to provide user-friendly free-to-use conversion tools that can convert the data into such standard formats in order to support wet-lab scientists in creating proteomics data files ready for upload into the public repositories. ProCon is such a conversion tool written in Java for conversion of proteomics identification data into standard formats mzIdentML and Pride XML. It allows the conversion of Sequest™/Comet .out files, of search results from the popular and often used ProteomeDiscoverer® 1.x (x=versions 1.1 to1.4) software and search results stored in the LIMS systems ProteinScape® 1.3 and 2.1 into mzIdentML and PRIDE XML. This article is part of a Special Issue entitled: Computational Proteomics. PMID:26182917

  7. Novel biomarkers in acute heart failure: MR-pro-adrenomedullin.

    PubMed

    Peacock, W Frank

    2014-10-01

    First isolated from human pheochromocytoma cells, adrenomedullin (ADM) is a peptide hormone with natriuretic, vasodilatory, and hypotensive effects mediated by cyclic adenosine monophosphate (cAMP), nitric oxide, and renal prostaglandin systems. ADM expression occurs in many tissues and organ systems, including cardiovascular, renal, pulmonary, cerebrovascular, gastrointestinal, and endocrine tissues where it acts as a circulating hormone and a local autocrine and paracrine hormone. ADM plasma concentrations are increased in hypertension, chronic renal disease, and heart failure. As ADM is unstable in vitro, it is necessary to measure its mid-regional pro-hormone fragment, the levels of which correspond to ADM concentration (MR-proADM). The prognostic potential of MR-proADM was recently demonstrated in the Biomarkers in Acute Heart Failure (BACH) trial. In this trial of 568 acute heart failure patients, MR-proADM was superior to both brain natriuretic peptide (BNP) and NT-proBNP in predicting mortality within 14 days. MR-proADM also provided significant additive incremental predictive value for 90-day mortality when added to BNP and NT-proBNP. PMID:24756062

  8. New developments in the InterPro database.

    PubMed

    Mulder, Nicola J; Apweiler, Rolf; Attwood, Teresa K; Bairoch, Amos; Bateman, Alex; Binns, David; Bork, Peer; Buillard, Virginie; Cerutti, Lorenzo; Copley, Richard; Courcelle, Emmanuel; Das, Ujjwal; Daugherty, Louise; Dibley, Mark; Finn, Robert; Fleischmann, Wolfgang; Gough, Julian; Haft, Daniel; Hulo, Nicolas; Hunter, Sarah; Kahn, Daniel; Kanapin, Alexander; Kejariwal, Anish; Labarga, Alberto; Langendijk-Genevaux, Petra S; Lonsdale, David; Lopez, Rodrigo; Letunic, Ivica; Madera, Martin; Maslen, John; McAnulla, Craig; McDowall, Jennifer; Mistry, Jaina; Mitchell, Alex; Nikolskaya, Anastasia N; Orchard, Sandra; Orengo, Christine; Petryszak, Robert; Selengut, Jeremy D; Sigrist, Christian J A; Thomas, Paul D; Valentin, Franck; Wilson, Derek; Wu, Cathy H; Yeats, Corin

    2007-01-01

    InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). The InterProScan search tool is now also available via a web service at http://www.ebi.ac.uk/Tools/webservices/WSInterProScan.html. PMID:17202162

  9. Fibrinogen Substrate Recognition by Staphylocoagulase·(Pro)thrombin Complexes*

    PubMed Central

    Panizzi, Peter; Friedrich, Rainer; Fuentes-Prior, Pablo; Richter, Klaus; Bock, Paul E.; Bode, Wolfram

    2008-01-01

    Thrombin generation and fibrinogen (Fbg) clotting are the ultimate proteolytic reactions in the blood coagulation pathway. Staphylocoagulase (SC), a protein secreted by the human pathogen Staphylococcus aureus, activates prothrombin (ProT) without proteolysis. The SC·(pro)thrombin complex recognizes Fbg as a specific substrate, converting it directly into fibrin. The crystal structure of a fully active SC fragment containing residues 1–325 (SC-(1–325)) bound to human prethrombin 2 showed previously that SC inserts its Ile1-Val2 N terminus into the Ile16 pocket of prethrombin 2, inducing a functional active site in the cognate zymogen conformationally. Exosite I of α-thrombin, the Fbg recognition site, and proexosite I on ProT are blocked by domain 2 of SC-(1–325). In the present studies, active site-labeled fluorescent ProT analogs were used to quantitate Fbg binding to the SC-(1–325)·ProT complex. Fbg binding and cleavage are mediated by expression of a new Fbg-binding exosite on the SC-(1–325)·ProT complex, resulting in formation of an (SC-(1–325)·ProT)2·Fbg pentameric complex with a dissociation constant of 8–34 nM. In both crystal structures, the SC-(1–325)·(pre)thrombin complexes form dimers, with both pro-teinases/zymogens facing each other over a large U-shaped cleft, through which the Fbg substrate could thread. On this basis, a molecular model of the pentameric (SC-(1–325)·thrombin)2·Fbg encounter complex was generated, which explains the coagulant properties and efficient Fbg conversion. The results provide new insight into the mechanism that mediates high affinity Fbg binding and cleavage as a substrate of SC·(pro)thrombin complexes, a process that is central to the molecular pathology of S. aureus endocarditis. PMID:16230339

  10. Manduca sexta prophenoloxidase (proPO) activation requires proPO-activating proteinase (PAP) and serine proteinase homologs (SPHs) simultaneously.

    PubMed

    Gupta, Snehalata; Wang, Yang; Jiang, Haobo

    2005-03-01

    In the tobacco hornworm Manduca sexta, proteolytic activation of prophenoloxidase (proPO) is mediated by three proPO-activating proteinases (PAPs) and two serine proteinase homologs (SPHs) (Proceedings of the National Academy of Sciences, USA 95 (1998) 12220-12225; J. Biol. Chem. 278 (2003a) 3552-3561; Insect Biochem. Mol. Biol. 33 (2003b) 1049-1060). While our current data are consistent with the hypothesis that the SPHs serve as a cofactor/anchor for PAPs (Insect Biochemistry and Molecular Biology 33 (2003) 197-208; Insect Biochemistry and Molecular Biology 34 (2004) 731-742), roles of these clip-domain proteins (i.e. PAPs and SPHs) in proPO activation are poorly defined. To better understand this process, we further characterized the activation reaction using proPO, PAP-1 and SPHs. PAP-1 itself cleaved nearly 1/3 of proPO at Arg51 without generating much phenoloxidase (PO) activity. In the presence of SPHs, the cleavage of proPO became more complete while the increase in PO activity was over 20-fold, indicating that the extent of cleavage does not directly correlate with PO activity. Since SPHs and p-amidinophenyl methanesulfonyl fluoride (APMSF)-treated PAP-1 did not generate active PO by interacting with proPO, proteolytic cleavage is critical for proPO activation. After 1/5 of proPO was processed by PAP-1 alone which was then inactivated by M. sexta serpin-1J or APMSF, further incubation of the reaction mixture with SPHs failed to generate active PO either. Thus, SPHs cannot generate PO activity by simply binding to cleaved proPO. M. sexta proPO activation requires active PAP-1 and SPHs at the same time-one for limited proteolysis and the other as a cofactor, perhaps. Gel filtration chromatography and native gel electrophoresis revealed the PAP-SPH, proPO-PAP, and SPH-proPO associations, essential for generating high Mr, active PO at the site of infection. PMID:15705503

  11. Pro/con a precessional geodynamo

    NASA Astrophysics Data System (ADS)

    Vanyo, J.

    2003-04-01

    The modest amount of research that exists on the ability, or lack of ability, of mantle precession to power a geodynamo developed mostly during the last half of the 1900s. Papers by Roberts and Stewartson (1965) and by Busse (1968) studied precession generally without a pro/con conclusion. Malkus in the late 1960s attempted to advance a positive role for precession through experiments and analysis. His experiments have survived criticism, but his analyses were discounted, especially by Rochester, Jacobs, Smylie, and Chong (1975) and by Loper (1975). Rochester, et al. critiqued existing analyses of precession, including those of Malkus, but did not reach a strong position either pro or con a precessional geodynamo. Loper argued emphatically that precession was not capable of powering the geodynamo. Explicit analyses that either critique or support Loper’s arguments have yet to appear in the literature. During the 1970s, Vanyo and associates studied energy dissipation during precession of satellite liquid fuels and its effect on satellite attitude stability. Engineers and scientists in every country that has launched satellites completed similar research. Some is published in the aerospace literature, more is available in company and government reports. Beginning in 1981, Vanyo and associates applied this knowledge to the very similar problem of energy dissipation and flow patterns in precessing mechanical models scaled geometrically and dynamically to the Earth’s liquid core. Energy experiments indicate massive amounts of mechanical energy are dissipated at the CMB, and flow experiments show complex motions within the boundary layer and axial flows with helicity throughout the interior. Analysis of Earth core precession also advanced, especially in several papers by Kerswell and by Tilgner in the late 1990s. Detail numerical models have yet to appear. Although progress in understanding the role of precession in Earth core motions has advanced, there remains a

  12. Simultaneous determination of pradefovir, PMEA and tenofovir in HBV patient serum using liquid chromatography-tandem mass spectrometry and application to phase 2 clinical trial.

    PubMed

    Xiao, Qingqing; Wang, Dan; Yang, Wanqiu; Chen, Lin; Ding, Yitao; Yang, Jin

    2016-06-01

    Pradefovir, a prodrug of PMEA, is under phase 2 clinical trial in China to evaluate its pharmacokinetic and pharmacodynamics after multiple-dose study, with adefovir dipivoxil and tenofovir disoproxil fumarate as positive control. A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of pradefovir, PMEA and tenofovir in HBV patient serum. Serum samples were pretreated via simple protein precipitation with methanol and entecavir was used as internal standard. Chromatographic separation was carried out on a Synergi(®) fusion-RP column (150mm×4.6mm) by gradient elution with methanol and 0.1% formic acid in water (v/v) at a flow rate of 1mL/min. The analytes were detected in multiple reaction monitoring mode with positive ion electrospray ionization at m/z 424.1/151.0, 274.1/162.2, 288.1/176.1, and 278.1/152.2for pradefovir, PMEA, tenofovir and IS, respectively. The assays were validated according to current bioanalytical guidelines including specificity, linearity (2.0-500ng/mL for pradefovir and PMEA, 4.0-1000ng/mL for tenofovir), accuracy and precision, extraction recovery, matrix effect and stability. The validated method has been successfully applied to the pharmacokinetic study of pradefovir, adefovir dipivoxil and tenofovir disoproxil fumarate in a set of HBV patients. PMID:27089519

  13. Pegylated Interferon α-2a Triggers NK-Cell Functionality and Specific T-Cell Responses in Patients with Chronic HBV Infection without HBsAg Seroconversion

    PubMed Central

    Bruder Costa, Juliana; Dufeu-Duchesne, Tania; Leroy, Vincent; Bertucci, Inga; Bouvier-Alias, Magali; Pouget, Noelle; Brevot-Lutton, Ophelie; Bourliere, Marc; Zoulim, Fabien

    2016-01-01

    Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment. PMID:27348813

  14. Pegylated Interferon α-2a Triggers NK-Cell Functionality and Specific T-Cell Responses in Patients with Chronic HBV Infection without HBsAg Seroconversion.

    PubMed

    Bruder Costa, Juliana; Dufeu-Duchesne, Tania; Leroy, Vincent; Bertucci, Inga; Bouvier-Alias, Magali; Pouget, Noelle; Brevot-Lutton, Ophelie; Bourliere, Marc; Zoulim, Fabien; Plumas, Joel; Aspord, Caroline

    2016-01-01

    Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment. PMID:27348813

  15. Aspartate aminotransferase-lymphocyte ratio index and systemic immune-inflammation index predict overall survival in HBV-related hepatocellular carcinoma patients after transcatheter arterial chemoembolization

    PubMed Central

    Yang, Zongguo; Zhang, Jianliang; Lu, Yunfei; Xu, Qingnian; Tang, Bozong; Wang, Qiang; Zhang, Wensi; Chen, Shishi; Lu, Lingqing; Chen, Xiaorong

    2015-01-01

    It has been suggested that lymphocytes play central roles in host antitumor immune responses and control cancer outcome. We reviewed the clinical parameters of 189 hepatocellular carcinoma (HCC) patients and investigated the prognostic significance of lymphocyte-related scores in HCC patients following transcatheter arterial chemoembolization (TACE). Survival analysis revealed that an elevated aspartate aminotransferase-lymphocyte ratio index (ALRI) > 57 and a systemic immune-inflammation index (SII) > 300 were negatively associated with overall survival in HBV-related HCC (HR = 2.181, P = 0.003 and HR = 2.453, P = 0.003; respectively). Spearman chi-square analysis showed that ALRI had a specificity of 82.4% and that SII index had a sensitivity of 71.9% for HCC overall survival. ALRI and SII had negative predictive values of 74.6% and 80%, respectively for HCC overall survival. Additionally, Barcelona Clinic Liver Cancer (BCLC) stage C patients had significantly higher ALRI and SII scores (both P < 0.0001) and poorer overall survival (HR = 3.618, P < 0.001). Additionally, HCC patients with portal vein tumor thrombosis (PVTT) had higher ALRI and SII scores (P < 0.0001 and P = 0.0059, respectively). In conclusion, as noninvasive, low cost, easily assessable and reproducible parameters, elevated ALRI and SII should be used as negative predictive factors for overall survival in HBV-related HCC in clinical practice. PMID:26506519

  16. Sensitivity of Low Flow Simulations by the HBV-EC Hydrological Model to the Choice of Downscaling Algorithm, Climate Predictors, and Global Climate Model

    NASA Astrophysics Data System (ADS)

    Cannon, A. J.

    2006-12-01

    Hydrological models are one of the main tools used to investigate low flows under future climate change scenarios. Climate data requirements range from high-resolution spatially gridded datasets for distributed hydrological models to site measurements for conceptual hydrological models. In either case, climatological information from coarse resolution Global Climate Models (GCMs) must be used to infer climate series at higher resolutions required by the hydrological models. This is typically done using a procedure known as climate downscaling. The effect of the choice of downscaling algorithm, synoptic-scale predictor dataset, and GCM on the sensitivity of low flow simulations by the HBV-EC hydrological model is the main focus of this study. Different statistical downscaling algorithms (an analog model, a non-parametric weather generator, and a conditional density artificial neural network), predictor datasets (drawn from global atmospheric model reanalyses), and GCMs (the Meteorological Service of Canada's CGCM2, the UK Met Office's HadCM3, and the US Department of Energy sponsored PCM) are used to drive the HBV-EC hydrological model in mountainous watersheds of British Columbia, Canada. The ability of the modeling system to reproduce low flows is validated on historical data and simulated low flows are analyzed for future climate change scenarios.

  17. Patient with hepatocellular carcinoma related to prior acute arsenic intoxication and occult HBV: Epidemiological, clinical and therapeutic results after 14 years of follow-up

    PubMed Central

    Casanovas-Taltavull, Teresa; Ribes, Josepa; Berrozpe, Ana; Jordan, Sara; Casanova, Aurora; Sancho, Concha; Valls, Carles; Bosch, F Xavier

    2006-01-01

    Little is known about the long-term survivors of acute arsenic intoxication. We present here a clinical case report of a man with chronic hepatitis B virus (HBV) infection who developed hepatocellular carcinoma four years after acute arsenic poisoning. HBsAg was detected in serum in 1990 when he voluntarily donated blood. In 1991, the patient suffered from severe psychological depression that led him to attempt suicide by massive ingestion of an arsenic-containing rodenticide. He survived with polyneuropathy and paralysis of the lower limbs, and has been wheelchair-bound since then. During participation in a follow-up study conducted among HBV carriers, abdominal ultrasound detected a two-centimeter liver mass consistent with hepatocellular carcinoma. The tumor was confirmed by computed tomography (CT) and magnetic resonance image (MRI). Because of his significant comorbidity, the patient received palliative treatment with transarterial lipiodol chemoembolization (TACE) on three occasions (1996, 1997 and 1999). At his most recent visit in May 2005, the patient was asymptomatic, liver enzymes were normal and the tumor was in remission on ultrasound. PMID:16610011

  18. Antiviral activity of various interferons and pro-inflammatory cytokines in non-transformed cultured hepatocytes infected with hepatitis B virus.

    PubMed

    Isorce, Nathalie; Testoni, Barbara; Locatelli, Maëlle; Fresquet, Judith; Rivoire, Michel; Luangsay, Souphalone; Zoulim, Fabien; Durantel, David

    2016-06-01

    In HBV-infected patients, therapies with nucleoside analogues or IFNα remain ineffective in eradicating the infection. Our aim was to re-analyze the anti-HBV activity of a large panel of IFNs and cytokines in vitro using non-transformed cultured hepatocytes infected with HBV, to identify new immune-therapeutic options. HepaRG cells and primary human hepatocytes were infected with HBV and, when infection was established, treated with various concentrations of different IFNs or inflammatory cytokines. Viral parameters were evaluated by quantifying HBV nucleic acids by qPCR and Southern Blot, and secreted HBV antigens were evaluated using ELISA. The cytokines tested were type-I IFNs, IFNγ, type-III IFNs, TNFα, IL-6, IL-1β, IL-18 as well as nucleos(t)ide analogues tenofovir and ribavirin. Cytokines and drugs, with the exception of IL-18 and ribavirin, exhibited a suppressive effect on HBV replication at least as strong as, but often stronger than, IFNα. The cytokine presenting the highest effect on HBV DNA was IL-1β, which exerted its inhibition within picomolar range. Importantly, we noticed differential effects on other parameters (HBV RNA, HBeAg, HBsAg) between both IFNs and inflammatory cytokines, thus suggesting different mechanisms of action. The combination of IL-1β and already used therapies, i.e. IFNα or tenofovir, demonstrated a stronger or similar anti-HBV activity. IL-1β was found to have a very potent antiviral effect against HBV in vitro. HBV was previously shown to promptly inhibit IL-1β production in Kupffer cells. Strategies aiming at unlocking this inhibition and restoring local production of IL-1β may help to further inhibit HBV replication in vivo. PMID:26971407

  19. Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

    PubMed Central

    EL-SAGHIRE, HOUSSEIN; VANDEVOORDE, CHARLOT; OST, PIET; MONSIEURS, PIETER; MICHAUX, ARLETTE; DE MEERLEER, GERT; BAATOUT, SARAH; THIERENS, HUBERT

    2014-01-01

    Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18–24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation. PMID:24435511

  20. Structural requirements for processing of pro-adipokinetic hormone I.

    PubMed

    Rayne, R C; O'Shea, M

    1993-11-01

    We found that a seven-residue sequence in pro-adipokinetic hormone I (proAKH I) which precedes the endopeptidase cleavage site is predicted to form an omega loop. Molecular modelling experiments indicated that a stable omega loop may form at this site, and suggested that loop stability may depend on the C-terminal loop residue, Lys12. The importance of this residue in proAKH I processing was confirmed by the observation that replacement of Lys12 by thialysine, a Lys analog with an altered side chain, prevented processing in vivo. In addition we showed by molecular modelling that this side-chain alteration may prevent formation of an omega loop. Together, these approaches lead us to propose that an omega loop may serve as a recognition motif in proAKH I processing. PMID:8223647

  1. Project ProCEED: A Model for Developing Professional Excellence.

    ERIC Educational Resources Information Center

    Miller, Marilyn; Waddell, Michael G.

    1984-01-01

    Project ProCEED is a staff development model for promoting the type of professional excellence recommended in national educational reports. A six-month program designed and implemented by teachers and principals is examined. (DF)

  2. The ProDom database of protein domain families.

    PubMed Central

    Corpet, F; Gouzy, J; Kahn, D

    1998-01-01

    The ProDom database contains protein domain families generated from the SWISS-PROT database by automated sequence comparisons. It can be searched on the World Wide Web (http://protein.toulouse.inra. fr/prodom.html ) or by E-mail (prodom@toulouse.inra.fr) to study domain arrangements within known families or new proteins. Strong emphasis has been put on the graphical user interface which allows for interactive analysis of protein homology relationships. Recent improvements to the server include: ProDom search by keyword; links to PROSITE and PDB entries; more sensitive ProDom similarity search with BLAST or WU-BLAST; alignments of query sequences with homologous ProDom domain families; and links to the SWISS-MODEL server (http: //www.expasy.ch/swissmod/SWISS-MODEL.html ) for homology based 3-D domain modelling where possible. PMID:9399865

  3. The correlation between serum HBsAg levels and viral loads depends upon wild‐type and mutated HBV sequences rather than the HBeAg/anti‐HBe status

    PubMed Central

    Liu, Mo‐Han; Chen, Qin‐Yan; Harrison, Tim J.; Li, Guo‐Jian; Li, Hai; Wang, Xue‐Yan; Ju, Yu; Yang, Jin‐Ye

    2015-01-01

    Despite several studies regarding the correlation between serum HBsAg titers and viral loads, the association remains uncertain. Eighty‐nine individuals were selected randomly from a Chinese cohort of 2,258 subjects infected persistently with hepatitis B virus (HBV) for cross‐sectional and longitudinal analysis. Viral loads of mutant HBV are lower than those of wild type HBV. The serum HBsAg titers correlate positively with viral loads in both HBeAg positive and negative subjects (r = 0.449, P = 0.013; r = 0.300, P = 0.018, respectively). No correlation between serum HBsAg titer and viral loads was found in any of the four phases of chronic HBV infection. The serum HBsAg titers correlate positively with viral loads in the group with wild type sequences of the PreS/S, basal core promoter (BCP), and preC regions of HBV(r = 0.502, P = 0.040). However, the correlation was not seen in the group with mutations in these regions (r = 0.165, P = 0.257). The correlation between HBsAg titers and viral loads was seen in individuals with wild type PreS/S sequences but not in the subgroup with BCP double mutations or PreC stop mutation, although their sequences in the preS/S regions were wild type. All these findings were confirmed by the longitudinal analysis. In conclusion, the correlation between serum HBsAg levels and viral loads may not differ between HBeAg positive and negative individuals but may depend on wild‐type or mutated genomic sequences. Therefore, HBsAg quantitation may be used as a surrogate for viral loads in only wild‐type HBV infections. J. Med. Virol. 87:1351–1360, 2015. © 2015 Wiley Periodicals, Inc. PMID:25879734

  4. Robotics Vision for a Scouting Rover - PRoViScout

    NASA Astrophysics Data System (ADS)

    Paar, G.; Woods, M.; Pullan, D.; Proviscout Team

    2011-10-01

    The FP7-SPACE Project ProViScout (Planetary Robotics Vision Scout, scheduled from April 2010 to September 2012) aims to demonstrate the feasibility of vision-based autonomous sample identification & selection in combination with vision-based navigation for a long range scouting/exploration mission on a terrestrial planet along with the robotic elements required. The paper gives an overview of the PRoViScout technical and scientific objectives, envisaged solutions and achievements so far.

  5. Analysis and expansion of the role of the Escherichia coli protein ProQ.

    PubMed

    Sheidy, Daniel T; Zielke, Ryszard A

    2013-01-01

    The decrease in proline transport by the proline porter ProP in a ΔproQ strain has been well documented; however, the reason for this phenotype remains undefined. Previous studies have speculated that ProQ facilitates translation of proP mRNA. Here, we demonstrate that ProQ is enriched in the polysome fractions of sucrose gradient separations of E. coli lysates and the 30S fractions of lysates separated under conditions causing ribosomal subunit dissociation. Thus, ProQ is a bona fide ribosome associated protein. Analysis of proQ constructs lacking predicted structural domains implicates the N-terminal domain in ribosome association. Association with the ribosome appears to be mediated by an interaction with the mRNA being translated, as limited treatment of lysates with Micrococcal Nuclease maintains ribosome integrity but disrupts ProQ localization with polysomes. ProQ also fails to robustly bind to mRNA-free 70S ribosomes in vitro. Interestingly, deletion of proP does not disrupt the localization of ProQ with translating ribosomes, and deletion of proP in combination with the proU operon has no effect on ProQ localization. We also demonstrate that ProQ is necessary for robust biofilm formation, and this phenotype is independent of ProP. Binding studies were carried out using tryptophan fluorescence and in vitro transcribed proP mRNAs. proP is transcribed from two differentially regulated promoters, and ProQ interacts with proP mRNA transcribed from both promoters, as well as a control mRNA with similar affinities. In total, these data suggest that ProQ is positioned to function as a novel translational regulator, and its cellular role extends beyond its effects on proline uptake by ProP. PMID:24205389

  6. Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    1999-01-01

    NASA's Propulsive Small Expendable Deployer System experiment (ProSEDS) will demonstrate the use of an electrodynamic tether, basically a long, thin wire, for propulsion. An electrodynamic tether uses the same principles as electric motors in toys, appliances and computer disk drives, and generators in automobiles and power plants. When electrical current is flowing through the tether, a magnetic field is produced that pushes against the magnetic field of the Earth. For ProSEDS, the current in the tether results by virtue of the voltage generated when the tether moves through the Earth's magnetic field at more than 17,000 mph. This approach can produce drag thrust generating useable power. Since electrodynamic tethers require no propellant, they could substantially reduce the weight of the spacecraft and provide a cost-effective method of reboosting spacecraft. The initial flight of ProSEDS is scheduled to fly aboard an Air Force Delta II rocket in the summer of 2002. In orbit, ProSEDS will deploy from a Delta II second stage. It will be a 3.1-mile (5 kilometer) long, ultrathin base-wire cornected with a 6.2-mile (10 kilometer) long nonconducting tether. This photograph shows Less Johnson, a scientist at MSFC inspecting the nonconducting part of a tether as it exits a deployer similar to the one to be used in the ProSEDS experiment. The ProSEDS experiment is managed by the Space Transportation Directorate at MSFC.

  7. AdjudiPro{reg_sign} 2.0

    SciTech Connect

    Williams, D.; Connolly, J.; Simons, B.C.

    1996-12-31

    AdjudiPro, version 2.0, is the latest incarnation of United HealthCare`s patented physician claims adjudication expert system (US patent No. 5,359,509). Its core is an embedded expert system that contains the logic for processing 55% of all physician claim situations reviewed on United HealthCare`s managed care system. Certain physician services are reviewed as part of the claims adjudication process to ensure that submitted charges meet contractual, and other guidelines. In 1995, nearly $20 million in gross savings was realized through use of this system. Since its initial deployment in 1991-1992, there has been a steep increase in AdjudiPro`s processing volume. This increased demand created a number of issues that had to be addressed to ensure AdjudiPro`s continued viability and growth. As a result, much of the past three years was spent rearchitecting AdjudiPro to meet the increasing load placed on it, while achieving acceptable throughput. AdjudiPro is now an essentially real-time application, processing claims twenty-four hours a day, seven days a week. This paper describes the current AdjudiPro application, and the key issues faced during the past three years.

  8. Recombinant medaka (Oryzias melastigmus) pro-hepcidin: Multifunctional characterization.

    PubMed

    Cai, Ling; Cai, Jing-Jing; Liu, Hai-Peng; Fan, Dan-Qing; Peng, Hui; Wang, Ke-Jian

    2012-02-01

    Recently, two hepcidin variant genes (Om-hep1 and Om-hep2) were identified in a model fish marine medaka and both were highly induced in vivo with bacterial challenge, suggesting that the medaka hepcidin may have a similar function to other reported teleostean hepcidins. In the present study, the antibacterial, antiviral and antitumor activities of Om-hep1 were determined using its synthetic and recombinant pro-peptides. The recombinant pro-hepcidin1 was expressed in Escherichia coli and an effective method to produce recombinant Pro-Omhep1 was developed in order to obtain a right folded structure. The results showed that both the synthetic mature peptide and recombinant pro-peptide had similar antibacterial activity against Gram-positive and negative bacteria. In particular, both the synthetic mature Om-hep1 and recombinant Pro-Omhep1 inhibited the viral replication of white spot syndrome virus in the hematopoietic tissue cells of the crayfish Cherax quadricarinatus. Om-hep1 also presented antitumor activity on the cultured human hepatocellular carcinoma cells. In addition, the antimicrobial mechanism of Om-hep1 was measured and it was found that Om-hep1 was likely to be non-membranolytic. The recombinant Pro-Omhep1 performed better biological activity compared to the synthetic mature Om-hep1. This study suggested that Om-hep1 was likely to be an important multifunction protein involved in various resistance actions in the marine medaka immune system. PMID:22051539

  9. InterPro: the integrative protein signature database.

    PubMed

    Hunter, Sarah; Apweiler, Rolf; Attwood, Teresa K; Bairoch, Amos; Bateman, Alex; Binns, David; Bork, Peer; Das, Ujjwal; Daugherty, Louise; Duquenne, Lauranne; Finn, Robert D; Gough, Julian; Haft, Daniel; Hulo, Nicolas; Kahn, Daniel; Kelly, Elizabeth; Laugraud, Aurélie; Letunic, Ivica; Lonsdale, David; Lopez, Rodrigo; Madera, Martin; Maslen, John; McAnulla, Craig; McDowall, Jennifer; Mistry, Jaina; Mitchell, Alex; Mulder, Nicola; Natale, Darren; Orengo, Christine; Quinn, Antony F; Selengut, Jeremy D; Sigrist, Christian J A; Thimma, Manjula; Thomas, Paul D; Valentin, Franck; Wilson, Derek; Wu, Cathy H; Yeats, Corin

    2009-01-01

    The InterPro database (http://www.ebi.ac.uk/interpro/) integrates together predictive models or 'signatures' representing protein domains, families and functional sites from multiple, diverse source databases: Gene3D, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. Integration is performed manually and approximately half of the total approximately 58,000 signatures available in the source databases belong to an InterPro entry. Recently, we have started to also display the remaining un-integrated signatures via our web interface. Other developments include the provision of non-signature data, such as structural data, in new XML files on our FTP site, as well as the inclusion of matchless UniProtKB proteins in the existing match XML files. The web interface has been extended and now links out to the ADAN predicted protein-protein interaction database and the SPICE and Dasty viewers. The latest public release (v18.0) covers 79.8% of UniProtKB (v14.1) and consists of 16 549 entries. InterPro data may be accessed either via the web address above, via web services, by downloading files by anonymous FTP or by using the InterProScan search software (http://www.ebi.ac.uk/Tools/InterProScan/). PMID:18940856

  10. New developments in the InterPro database

    PubMed Central

    Mulder, Nicola J.; Apweiler, Rolf; Attwood, Teresa K.; Bairoch, Amos; Bateman, Alex; Binns, David; Bork, Peer; Buillard, Virginie; Cerutti, Lorenzo; Copley, Richard; Courcelle, Emmanuel; Das, Ujjwal; Daugherty, Louise; Dibley, Mark; Finn, Robert; Fleischmann, Wolfgang; Gough, Julian; Haft, Daniel; Hulo, Nicolas; Hunter, Sarah; Kahn, Daniel; Kanapin, Alexander; Kejariwal, Anish; Labarga, Alberto; Langendijk-Genevaux, Petra S.; Lonsdale, David; Lopez, Rodrigo; Letunic, Ivica; Madera, Martin; Maslen, John; McAnulla, Craig; McDowall, Jennifer; Mistry, Jaina; Mitchell, Alex; Nikolskaya, Anastasia N.; Orchard, Sandra; Orengo, Christine; Petryszak, Robert; Selengut, Jeremy D.; Sigrist, Christian J. A.; Thomas, Paul D.; Valentin, Franck; Wilson, Derek; Wu, Cathy H.; Yeats, Corin

    2007-01-01

    InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (), and for download by anonymous FTP (). The InterProScan search tool is now also available via a web service at . PMID:17202162

  11. InterPro: the integrative protein signature database

    PubMed Central

    Hunter, Sarah; Apweiler, Rolf; Attwood, Teresa K.; Bairoch, Amos; Bateman, Alex; Binns, David; Bork, Peer; Das, Ujjwal; Daugherty, Louise; Duquenne, Lauranne; Finn, Robert D.; Gough, Julian; Haft, Daniel; Hulo, Nicolas; Kahn, Daniel; Kelly, Elizabeth; Laugraud, Aurélie; Letunic, Ivica; Lonsdale, David; Lopez, Rodrigo; Madera, Martin; Maslen, John; McAnulla, Craig; McDowall, Jennifer; Mistry, Jaina; Mitchell, Alex; Mulder, Nicola; Natale, Darren; Orengo, Christine; Quinn, Antony F.; Selengut, Jeremy D.; Sigrist, Christian J. A.; Thimma, Manjula; Thomas, Paul D.; Valentin, Franck; Wilson, Derek; Wu, Cathy H.; Yeats, Corin

    2009-01-01

    The InterPro database (http://www.ebi.ac.uk/interpro/) integrates together predictive models or ‘signatures’ representing protein domains, families and functional sites from multiple, diverse source databases: Gene3D, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. Integration is performed manually and approximately half of the total ∼58 000 signatures available in the source databases belong to an InterPro entry. Recently, we have started to also display the remaining un-integrated signatures via our web interface. Other developments include the provision of non-signature data, such as structural data, in new XML files on our FTP site, as well as the inclusion of matchless UniProtKB proteins in the existing match XML files. The web interface has been extended and now links out to the ADAN predicted protein–protein interaction database and the SPICE and Dasty viewers. The latest public release (v18.0) covers 79.8% of UniProtKB (v14.1) and consists of 16 549 entries. InterPro data may be accessed either via the web address above, via web services, by downloading files by anonymous FTP or by using the InterProScan search software (http://www.ebi.ac.uk/Tools/InterProScan/). PMID:18940856

  12. Synthesis, DNA recognition and cleavage studies of novel tetrapeptide complexes, Cu(II)/Zn(II)-Ala-Pro-Ala-Pro

    NASA Astrophysics Data System (ADS)

    Arjmand, Farukh; Jamsheera, A.; Mohapatra, D. K.

    2013-05-01

    New tetrapeptide complexes Cu(II)·Ala-Pro-Ala-Pro (1) and Zn(II)·Ala-Pro-Ala-Pro (2) were synthesized from the reaction of tetrapeptide, Ala-Pro-Ala-Pro and CuCl2/ZnCl2 and were thoroughly characterized by elemental analysis, IR,1H and 13C NMR (in case of 2), ESI-MS, UV and molar conductance measurements. The solution stability study was carried out employing UV-vis absorption titrations over a broad range of pH which suggested the stability of the complexes in solution. In vitro interaction of complexes 1 and 2 with CT-DNA was studied employing UV-vis, fluorescence, circular dichroic and viscometry studies. To throw insight into molecular binding event at the target site, UV-vis titrations of 1 and 2 with mononucleotides of interest viz.; 5'-GMP and 5'-TMP were carried out. Cleavage activity of the complexes with pBR322 plasmid DNA was evaluated by agarose gel electrophoresis and, the electrophoresis pattern demonstrated that both the complexes 1 and 2 are efficient cleavage agents. Further, the Cu(II) complex displayed efficient oxidative cleavage of supercoiled DNA while various reactive oxygen species are responsible for the cleavage in Zn(II) complex.

  13. The InterPro BioMart: federated query and web service access to the InterPro Resource.

    PubMed

    Jones, Philip; Binns, David; McMenamin, Conor; McAnulla, Craig; Hunter, Sarah

    2011-01-01

    The InterPro BioMart provides users with query-optimized access to predictions of family classification, protein domains and functional sites, based on a broad spectrum of integrated computational models ('signatures') that are generated by the InterPro member databases: Gene3D, HAMAP, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. These predictions are provided for all protein sequences from both the UniProt Knowledge Base and the UniParc protein sequence archive. The InterPro BioMart is supplementary to the primary InterPro web interface (http://www.ebi.ac.uk/interpro), providing a web service and the ability to build complex, custom queries that can efficiently return thousands of rows of data in a variety of formats. This article describes the information available from the InterPro BioMart and illustrates its utility with examples of how to build queries that return useful biological information. Database URL: http://www.ebi.ac.uk/interpro/biomart/martview. PMID:21785143

  14. 78 FR 32281 - ProShares Advisors LLC, et al.; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-29

    ... COMMISSION ProShares Advisors LLC, et al.; Notice of Application May 21, 2013. AGENCY: Securities and... exemption from sections 12(d)(1)(A) and (B) of the Act. Applicants: ProShares Advisors LLC (``ProShares''), ProShares Trust (the ``Trust''), and SEI Investments Distribution Co. (``SEI''). Summary...

  15. Establishment of an inducible HBV stable cell line that expresses cccDNA-dependent epitope-tagged HBeAg for screening of cccDNA modulators.

    PubMed

    Cai, Dawei; Wang, Xiaohe; Yan, Ran; Mao, Richeng; Liu, Yuanjie; Ji, Changhua; Cuconati, Andrea; Guo, Haitao

    2016-08-01

    Hepatitis B virus (HBV) covalently closed circular (ccc) DNA is essential to the virus life cycle, its elimination during chronic infection is considered critical to a durable therapy but has not been achieved by current antivirals. Despite being essential, cccDNA has not been the major target of high throughput screening (HTS), largely because of the limitations of current HBV tissue culture systems, including the impracticality of detecting cccDNA itself. In response to this need, we have previously developed a proof-of-concept HepDE19 cell line in which the production of wildtype e antigen (HBeAg) is dependent upon cccDNA. However, the existing assay system is not ideal for HTS because the HBeAg ELISA cross reacts with a viral HBeAg homologue, which is the core antigen (HBcAg) expressed largely in a cccDNA-independent fashion in HepDE19 cells. To further improve the assay specificity, we report herein a "second-generation" cccDNA reporter cell line, termed HepBHAe82. In the similar principle of HepDE19 line, an in-frame HA epitope tag was introduced into the precore domain of HBeAg open reading frame in the transgene of HepBHAe82 cells without disrupting any cis-element critical for HBV replication and HBeAg secretion. A chemiluminescence ELISA assay (CLIA) for the detection of HA-tagged HBeAg with HA antibody serving as capture antibody and HBeAb serving as detection antibody has been developed to eliminate the confounding signal from HBcAg. The miniaturized HepBHAe82 cell based assay system exhibits high level of cccDNA-dependent HA-HBeAg production and high specific readout signals with low background. We have also established a HepHA-HBe4 cell line expressing transgene-dependent HA-HBeAg as a counter screen to identify HBeAg inhibitors. The HepBHAe82 system is amenable to antiviral HTS development, and can be used to identify host factors that regulate cccDNA metabolism and transcription. PMID:27185623

  16. Greater Drug Injecting Risk for HIV, HBV, and HCV Infection in a City Where Syringe Exchange and Pharmacy Syringe Distribution are Illegal

    PubMed Central

    Zhao, Mingfang; Gyarmathy, V. Anna; Cisek, Linda; Friedman, Samuel R.; Baxter, Robert C.

    2008-01-01

    Comparing drug-injecting risk between cities that differ in the legality of sterile syringe distribution for injection drug use provides a natural experiment to assess the efficacy of legalizing sterile syringe distribution as a structural intervention to prevent human immunodeficiency virus (HIV) and other parenterally transmitted infections among injection drug users (IDUs). This study compares the parenteral risk for HIV and hepatitis B (HBV) and C (HCV) infection among IDUs in Newark, NJ, USA, where syringe distribution programs were illegal during the period when data were collected, and New York City (NYC) where they were legal. IDUs were nontreatment recruited, 2004–2006, serotested, and interviewed about syringe sources and injecting risk behaviors (prior 30 days). In multivariate logistic regression, adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) for city differences are estimated controlling for potential city confounders. IDUs in Newark (n = 214) vs. NYC (n = 312) were more likely to test seropositive for HIV (26% vs. 5%; AOR = 3.2; 95% CI = 1.6, 6.1), antibody to the HBV core antigen (70% vs. 27%; AOR = 4.4; 95% CI = 2.8, 6.9), and antibody to HCV (82% vs. 53%; AOR = 3.0; 95% CI = 1.8, 4.9), were less likely to obtain syringes from syringe exchange programs or pharmacies (AOR = 0.004; 95% CI = 0.001, 0.01), and were more likely to obtain syringes from street sellers (AOR = 74.0; 95% CI = 29.9, 183.2), to inject with another IDU’s used syringe (AOR = 2.3; 95% CI = 1.1, 5.0), to reuse syringes (AOR = 2.99; 95% CI = 1.63, 5.50), and to not always inject once only with a new, sterile syringe that had been sealed in a wrapper (AOR = 5.4; 95% CI = 2.9, 10.3). In localities where sterile syringe distribution is illegal, IDUs are more likely to obtain syringes from unsafe sources and to engage in injecting risk behaviors. Legalizing and rapidly implementing sterile

  17. Frequency and genotypic distribution of GB virus C (GBV-C) among Colombian population with Hepatitis B (HBV) or Hepatitis C (HCV) infection

    PubMed Central

    2011-01-01

    Background GB virus C (GBV-C) is an enveloped positive-sense ssRNA virus belonging to the Flaviviridae family. Studies on the genetic variability of the GBV-C reveals the existence of six genotypes: genotype 1 predominates in West Africa, genotype 2 in Europe and America, genotype 3 in Asia, genotype 4 in Southwest Asia, genotype 5 in South Africa and genotype 6 in Indonesia. The aim of this study was to determine the frequency and genotypic distribution of GBV-C in the Colombian population. Methods Two groups were analyzed: i) 408 Colombian blood donors infected with HCV (n = 250) and HBV (n = 158) from Bogotá and ii) 99 indigenous people with HBV infection from Leticia, Amazonas. A fragment of 344 bp from the 5' untranslated region (5' UTR) was amplified by nested RT PCR. Viral sequences were genotyped by phylogenetic analysis using reference sequences from each genotype obtained from GenBank (n = 160). Bayesian phylogenetic analyses were conducted using Markov chain Monte Carlo (MCMC) approach to obtain the MCC tree using BEAST v.1.5.3. Results Among blood donors, from 158 HBsAg positive samples, eight 5.06% (n = 8) were positive for GBV-C and from 250 anti-HCV positive samples, 3.2%(n = 8) were positive for GBV-C. Also, 7.7% (n = 7) GBV-C positive samples were found among indigenous people from Leticia. A phylogenetic analysis revealed the presence of the following GBV-C genotypes among blood donors: 2a (41.6%), 1 (33.3%), 3 (16.6%) and 2b (8.3%). All genotype 1 sequences were found in co-infection with HBV and 4/5 sequences genotype 2a were found in co-infection with HCV. All sequences from indigenous people from Leticia were classified as genotype 3. The presence of GBV-C infection was not correlated with the sex (p = 0.43), age (p = 0.38) or origin (p = 0.17). Conclusions It was found a high frequency of GBV-C genotype 1 and 2 in blood donors. The presence of genotype 3 in indigenous population was previously reported from Santa Marta region in Colombia and

  18. GeoPro: Technology to Enable Scientific Modeling

    SciTech Connect

    C. Juan

    2004-02-09

    Development of the ground-water flow model for the Death Valley Regional Groundwater Flow System (DVRFS) required integration of numerous supporting hydrogeologic investigations. The results from recharge, discharge, hydraulic properties, water level, pumping, model boundaries, and geologic studies were integrated to develop the required conceptual and 3-D framework models, and the flow model itself. To support the complex modeling process and the needs of the multidisciplinary DVRFS team, a hardware and software system called GeoPro (Geoscience Knowledge Integration Protocol) was developed. A primary function of GeoPro is to manage the large volume of disparate data compiled for the 100,000-square-kilometer area of southern Nevada and California. The data are primarily from previous investigations and regional flow models developed for the Nevada Test Site and Yucca Mountain projects. GeoPro utilizes relational database technology (Microsoft SQL Server{trademark}) to store and manage these tabular point data, groundwater flow model ASCII data, 3-D hydrogeologic framework data, 2-D and 2.5-D GIS data, and text documents. Data management consists of versioning, tracking, and reporting data changes as multiple users access the centralized database. GeoPro also supports the modeling process by automating the routine data transformations required to integrate project software. This automation is also crucial to streamlining pre- and post-processing of model data during model calibration. Another function of GeoPro is to facilitate the dissemination and use of the model data and results through web-based documents by linking and allowing access to the underlying database and analysis tools. The intent is to convey to end-users the complex flow model product in a manner that is simple, flexible, and relevant to their needs. GeoPro is evolving from a prototype system to a production-level product. Currently the DVRFS pre- and post-processing modeling tools are being re

  19. Structure and activation of pro-activin A.

    PubMed

    Wang, Xuelu; Fischer, Gerhard; Hyvönen, Marko

    2016-01-01

    Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein. PMID:27373274

  20. Regulation of autoimmune inflammation by pro-inflammatory cytokines

    PubMed Central

    Kim, Eugene Y.; Moudgil, Kamal D.

    2008-01-01

    The pro-inflammatory cytokines play a critical role in the initiation and propagation of autoimmune arthritis and many other disorders resulting from a dysregulated self-directed immune response. These cytokines influence the interplay among the cellular, immunological and biochemical mediators of inflammation at multiple levels. Regulation of the pro-inflammatory activity of these cytokines is generally perceived to be mediated by the anti-inflammatory and immunosuppressive cytokines such as IL-4, IL-10, or TGF-β. However, increasing evidence is accumulating in support of the regulatory attributes of the pro-inflammatory cytokines themselves, in studies conducted in animal models of diabetes, multiple sclerosis, uveitis, and lupus. The results of our recent studies have shown that the pro-inflammatory cytokines, TNF-α and IFN-γ, can suppress arthritic inflammation in rats, and also contribute to resistance against arthritis. These results are of paramount significance not only in fully understanding the pathogenesis of autoimmune arthritis, but also in anticipating the full ramifications of the in vivo neutralization of the pro-inflammatory cytokines, including that for therapeutic purposes. PMID:18694783

  1. Structure and activation of pro-activin A

    PubMed Central

    Wang, Xuelu; Fischer, Gerhard; Hyvönen, Marko

    2016-01-01

    Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein. PMID:27373274

  2. Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    Ballance, Judy; Johnson, Les; Rogacki, John R. (Technical Monitor)

    2000-01-01

    The Propulsive Small Expendable Deployer System (ProSEDS) space experiment will demonstrate the use of an electrodynamic tether propulsion system to generate thrust in space by decreasing the orbital altitude of a Delta II Expendable Launch Vehicle (ELV) second stage. ProSEDS, which is planned to fly in 2001, will use the flight proven Small Expendable Deployer System (SEDS) to deploy a tether (5km bare wire plus 10 km spectra or dyneema) from a Delta II second stage to achieve approximately 0.4N drag thrust. ProSEDS will utilize the tether-generated current to provide limited spacecraft power. The ProSEDs instrumentation includes a Langmuir probe and Differential Ion Flux Probe, which will determine the characteristics of the ambient ionospheric plasma. Two Global Positioning System (GPS) receivers will be used (one on the Delta and one on the endmass) to help determine tether dynamics and to limit transmitter operations to occasions when the spacecraft is over selected ground stations, The flight experiment is a precursor to the more ambitious electrodynamic tether upper stage demonstration mission, which will be capable of orbit raising, lowering and inclination changes-all using electrodynamic thrust. An immediate application of ProSEDS technology is for the deorbit of spent satellites for orbital debris mitigation. In addition to the use of this technology to provide orbit transfer and debris mitigation it may also be an attractive option for future missions to Jupiter and any other planetary body with a magnetosphere.

  3. Milk-Derived Tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) Promote Adipocyte Differentiation and Inhibit Inflammation in 3T3-F442A Cells

    PubMed Central

    Chakrabarti, Subhadeep; Wu, Jianping

    2015-01-01

    Milk derived tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) have shown promise as anti-hypertensive agents due to their inhibitory effects on angiotensin converting enzyme (ACE). Due to the key inter-related roles of hypertension, chronic inflammation and insulin resistance in the pathogenesis of metabolic syndrome, there is growing interest in investigating established anti-hypertensive agents for their effects on insulin sensitivity and inflammation. In this study, we examined the effects of IPP and VPP on 3T3-F442A murine pre-adipocytes, a widely used model for studying metabolic diseases. We found that both IPP and VPP induced beneficial adipogenic differentiation as manifested by intracellular lipid accumulation, upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and secretion of the protective lipid hormone adiponectin by these cells. The observed effects were similar to those induced by insulin, suggesting potential benefits in the presence of insulin resistance. IPP and VPP also inhibited cytokine induced pro-inflammatory changes such as reduction in adipokine levels and activation of the nuclear factor kappa B (NF-κB) pathway. Taken together, our findings suggest that IPP and VPP exert insulin-mimetic adipogenic effects and prevent inflammatory changes in adipocytes, which may offer protection against metabolic disease. PMID:25714093

  4. Genome-wide association study identified PLCE1- rs2797992 and EGFR- rs6950826 were associated with TP53 expression in the HBV-related hepatocellular carcinoma of Chinese patients in Guangxi

    PubMed Central

    Liao, Xiwen; Han, Chuangye; Qin, Wei; Liu, Xiaoguang; Yu, Long; Lu, Sicong; Chen, Zhiwei; Zhu, Guangzhi; Su, Hao; Mo, Zengnan; Qin, Xue; Peng, Tao

    2016-01-01

    Objective: The genome-wide association approach was employed to explore the association between single nucleotide polymorphisms (SNPs) and TP53 expression in the HBV-related hepatocellular carcinoma (HCC) of Chinese patients in Guangxi. Methods: 403 HBV-related HCC patients were recruited into this study and classified according to the TP53 expression in the cancer by immunohistochemistry. DNA was extracted from the cancer and genotyped with the Human ExomeBeadChip 12v1-1 system; quality control and principal-component analysis (PCA) were applied for data analysis. Results: The Genome-wide association analysis indicated that rs2797992 with a P value of 4.35 × 10-5 locus in PLCE1 gene and rs6950826 with a P value of 2.2 × 10-3 locus in EGFR gene were associated with TP53 expression in the HCC. A allele of rs2797992 predicted a decreased risk for TP53 expression in HCC. In contrast, A allele of rs6950826 increased the risk for TP53 expression. There was no strong LD locus in the tested regions. PLCE1 and EGFR were associated with TP53 in pathway and at HCC mRNA level. Conclusion: rs2797992 of PLCE1 gene and rs6950826 of EGFR gene are associated with TP53 expression, but not with the prognosis of HBV-related HCC in HBV-related HCC of Chinese patients in Guangxi. PMID:27186304

  5. Natural history of chronic HBV infection: a cohort study with up to 12 years follow-up in North Greece (part of the Interreg I-II/EC-project).

    PubMed

    Zacharakis, G H; Koskinas, J; Kotsiou, S; Papoutselis, M; Tzara, F; Vafeiadis, N; Archimandritis, A J; Papoutselis, K

    2005-10-01

    The aim of the study was to assess the long-term outcome of chronic hepatitis B surface antigen (HBsAg) carriers in the general population in North Greece (Thrace), an area with an intermediate endemicity. This was a part of the Interreg I-II EC project. Two hundred sixty three chronic HBsAg+ carriers, median age 34 years (20-65), were evaluated prospectively for a median follow-up of 5 years (2-12). Hepatitis B virus (HBV) markers and ALT were examined every 6 months and serum HBV-DNA every 12 months. Liver biopsy was undertaken at presentation and every 2-4 years. Fourteen of 263 (5.3%) subjects were HBeAg+ and 249/263 (94.7%) HBeAg(-)/anti-HBe+ of whom 48 (19.3%) had elevated ALT, and HBV-DNA levels ranging from 1.4 x 10(5)-4 x 10(7) copies/ml. Inactive carriers (98/195 (50.3%)) had detectable HBV-DNA (median 2.6 x 10(3) range 0.042 x 10(4)-1.9 x 10(4) copies/ml); 4/195 (2%) exhibited HBV reactivation during the observation period (all had HBV-DNA >10(4) copies/ml at presentation). Patients (7/14 (50%) HBeAg+) developed anti-HBe+, annual rate 10%. Subjects (16/195 (8%)) lost HBsAg, all were inactive carriers; 10 developed anti-HBs (annual rate 1%). Liver biopsy was normal or with minimal changes in 92/95 (97%) inactive carriers and remained so at 4 years follow-up. In contrast, 4/48 (8.3%) HBeAg(-)/anti-HBe+ patients with active disease had deterioration of liver histology. In this cohort study: (a) the annual seroconversion rate was 1% for the HBsAg and 10% for the HBeAg, (b) 23.6% of the HBsAg+ carriers had active liver disease and 39% moderate fibrosis at presentation of whom a small proportion deteriorated over the observation period, (c) HBsAg carriers with HBV-DNA level <10(4) copies/ml had persistently normal ALT and unchanged liver histology over the follow-up period of up to 12 years. PMID:16121378

  6. Development of an in-House TaqMan Real-Time PCR-Based Method to Detect Residual Host Cell DNA in HBV Vaccine.

    PubMed

    Paryan, Mahdi; Khodayar, Mana; Kia, Vahid; Mohammadi-Yeganeh, Samira; Kaghazian, Hooman

    2016-06-01

    Biological therapeutic products such as recombinant hepatitis B virus (HBV) vaccine, produced by microbial fermentation in complex media, should be evaluated for host cell DNA contamination in purification steps. Eliminating these contaminations increases the efficacy of the vaccine and decreases its side effects. The objective of the present study is to trace the residual host cell DNA (HCD) in recombinant HBV vaccine by developing a TaqMan Real-Time PCR method which is more sensitive, specific, and reproducible than traditional methods such as Picogreen analysis and Threshold DNA assay. Primers and a probe were designed for the most highly conserved regions of Pichia pastoris genome. To determine the specificity of the assay, in addition to performing a BLAST for the primers and the probe in NCBI nucleotide database, 20 different human genomes and 8 bacterial and viral genomes were used. Moreover, serial dilutions of plasmids, from 10(2) to 10(7) copies/μL (from 0.00064 to 6.4 pg/μL), were prepared to find the sensitivity and the limit of detection (LOD) of the assay. Using 28 different genome samples, the specificity of the assay was determined to be 100 %. In addition, the sensitivity and LOD of the method was 0.39 × 10(-5) pg/μL. Moreover, the reproducibility of the assay based on intra- and inter-assay was 1.03 and 1.06 %, respectively. Considering the suitable specificity and sensitivity, ease of use, relatively low cost, and rapidity of the assay, it can be a reproducible and sensitive method to examine recombinant vaccines for P. pastoris residual DNA. PMID:26861732

  7. CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study.

    PubMed

    Cooper, C L; Davis, H L; Morris, M L; Efler, S M; Adhami, M Al; Krieg, A M; Cameron, D W; Heathcote, J

    2004-11-01

    Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN) act as potent Th1-like immune enhancers with many antigens in animal models. We have extended these observations to the first clinical evaluation of the safety, tolerability and immunogenicity of CPG 7909 when added to a commercial HBV vaccine. In a randomized, double-blind phase I dose escalation study, healthy volunteers aged 18-35 years were vaccinated at 0, 4 and 24 weeks by intramuscular injection with Engerix-B (GlaxoSmithKline). The regular adult dose of 20 microg recombinant hepatitis B surface antigen (HBsAg) adsorbed to alum was administered mixed with saline (control) or with CPG 7909 at one of three doses (0.125, 0.5 or 1.0 mg). HBsAg-specific antibody responses (anti-HBs) appeared significantly sooner and were significantly higher at all timepoints up to and including 24 weeks in CPG 7909 recipients compared to control subjects (p< or = 0.001). Strikingly, most CpG 7909-vaccinated subjects developed protective levels of anti-HBs IgG within just two weeks of the priming vaccine dose. A trend towards higher rates of positive cytotoxic T cell lymphocyte responses was noted in the two higher dose groups of CPG 7909 compared to controls. The most frequently reported adverse events were injection site reactions, flu-like symptoms and headache. While these were more frequent in CPG 7909 groups than in the control group (p<0.0001), most were reported to be of mild to moderate intensity regardless of group. In summary, CPG 7909 as an adjuvant to Engerix-B was well-tolerated and enhanced vaccine immunogenicity. CPG 7909 may allow the development of a two-dose prophylactic HBV vaccine. PMID:15622454

  8. Motoneuron Programmed Cell Death in Response to proBDNF

    PubMed Central

    Taylor, AR; Gifondorwa, DJ; Robinson, MB; Strupe, JL; Prevette, D; Johnson, JE; Hempstead, BL; Oppenheim, RW; Milligan, CE

    2011-01-01

    Motoneurons (MN) as well as most neuronal populations undergo a temporally and spatially specific period of programmed cell death (PCD). Several factors have been considered to regulate the survival of MNs during this period, including availability of muscle-derived trophic support and activity. The possibility that target-derived factors may also negatively regulate MN survival has been considered, but not pursued. Neurotrophin precursors, through their interaction with p75NTR and sortilin receptors have been shown to induce cell death during development and following injury in the CNS. In this study, we find that muscle cells produce and secrete proBDNF. ProBDNF through its interaction with p75NTR and sortilin, promotes a caspase-dependent death of MNs in culture. We also provide data to suggest that proBDNF regulates MN PCD during development in vivo. PMID:21834083

  9. Empathy and pro-social behavior in rats.

    PubMed

    Ben-Ami Bartal, Inbal; Decety, Jean; Mason, Peggy

    2011-12-01

    Whereas human pro-social behavior is often driven by empathic concern for another, it is unclear whether nonprimate mammals experience a similar motivational state. To test for empathically motivated pro-social behavior in rodents, we placed a free rat in an arena with a cagemate trapped in a restrainer. After several sessions, the free rat learned to intentionally and quickly open the restrainer and free the cagemate. Rats did not open empty or object-containing restrainers. They freed cagemates even when social contact was prevented. When liberating a cagemate was pitted against chocolate contained within a second restrainer, rats opened both restrainers and typically shared the chocolate. Thus, rats behave pro-socially in response to a conspecific's distress, providing strong evidence for biological roots of empathically motivated helping behavior. PMID:22158823

  10. The neuropsychology of infants’ pro-social preferences

    PubMed Central

    Gredebäck, Gustaf; Kaduk, Katharina; Bakker, Marta; Gottwald, Janna; Ekberg, Therese; Elsner, Claudia; Reid, Vincent; Kenward, Ben

    2015-01-01

    The current study is the first to investigate neural correlates of infants’ detection of pro- and antisocial agents. Differences in ERP component P400 over posterior temporal areas were found during 6-month-olds’ observation of helping and hindering agents (Experiment 1), but not during observation of identically moving agents that did not help or hinder (Experiment 2). The results demonstrate that the P400 component indexes activation of infants’ memories of previously perceived interactions between social agents. This leads to suggest that similar processes might be involved in infants’ processing of pro- and antisocial agents and other social perception processes (encoding gaze direction, goal directed grasping and pointing). PMID:25681955

  11. Pro-2-PAM therapy for central and peripheral cholinesterases.

    PubMed

    Demar, James C; Clarkson, Edward D; Ratcliffe, Ruthie H; Campbell, Amy J; Thangavelu, Sonia G; Herdman, Christine A; Leader, Haim; Schulz, Susan M; Marek, Elizabeth; Medynets, Marie A; Ku, Therese C; Evans, Sarah A; Khan, Farhat A; Owens, Roberta R; Nambiar, Madhusoodana P; Gordon, Richard K

    2010-09-01

    Novel therapeutics to overcome the toxic effects of organophosphorus (OP) chemical agents are needed due to the documented use of OPs in warfare (e.g. 1980-1988 Iran/Iraq war) and terrorism (e.g. 1995 Tokyo subway attacks). Standard OP exposure therapy in the United States consists of atropine sulfate (to block muscarinic receptors), the acetylcholinesterase (AChE) reactivator (oxime) pralidoxime chloride (2-PAM), and a benzodiazepine anticonvulsant to ameliorate seizures. A major disadvantage is that quaternary nitrogen charged oximes, including 2-PAM, do not cross the blood brain barrier (BBB) to treat brain AChE. Therefore, we have synthesized and evaluated pro-2-PAM (a lipid permeable 2-PAM derivative) that can enter the brain and reactivate CNS AChE, preventing seizures in guinea pigs after exposure to OPs. The protective effects of the pro-2-PAM after OP exposure were shown using (a) surgically implanted radiotelemetry probes for electroencephalogram (EEG), (b) neurohistopathology of brain, (c) cholinesterase activities in the PNS and CNS, and (d) survivability. The PNS oxime 2-PAM was ineffective at reducing seizures/status epilepticus (SE) in diisopropylfluorophosphate (DFP)-exposed animals. In contrast, pro-2-PAM significantly suppressed and then eliminated seizure activity. In OP-exposed guinea pigs, there was a significant reduction in neurological damage with pro-2-PAM but not 2-PAM. Distinct regional areas of the brains showed significantly higher AChE activity 1.5h after OP exposure in pro-2-PAM treated animals compared to the 2-PAM treated ones. However, blood and diaphragm showed similar AChE activities in animals treated with either oxime, as both 2-PAM and pro-2-PAM are PNS active oximes. In conclusion, pro-2-PAM can cross the BBB, is rapidly metabolized inside the brain to 2-PAM, and protects against OP-induced SE through restoration of brain AChE activity. Pro-2-PAM represents the first non-invasive means of administering a CNS therapeutic for

  12. Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts

    PubMed Central

    Gurney, Mark; Mason, Malcolm D.; Tabi, Zsuzsanna; Clayton, Aled

    2015-01-01

    Stromal fibroblasts become altered in response to solid cancers, to exhibit myofibroblastic characteristics, with disease promoting influence. Infiltrating mesenchymal stem cells (MSC) may contribute towards these changes, but the factors secreted by cancer cells that impact MSC differentiation are poorly understood. We investigated the role of nano-metre sized vesicles (exosomes), secreted by prostate cancer cells, on the differentiation of bone-marrow MSC (BM-MSC), and the subsequent functional consequences of such changes. Purified exosomes impaired classical adipogenic differentiation, skewing differentiation towards alpha-smooth muscle actin (αSMA) positive myofibroblastic cells. A single exosomes treatment generated myofibroblasts secreting high levels of VEGF-A, HGF and matrix regulating factors (MMP-1, −3 and −13). Differentiated MSC had pro-angiogenic functions and enhanced tumour proliferation and invasivity assessed in a 3D co-culture model. Differentiation was dependent on exosomal-TGFβ, but soluble TGFβ at matched dose could not generate the same phenotype. Exosomes present in the cancer cell secretome were the principal factors driving this phenotype. Prostate cancer exosomes dominantly dictate a programme of MSC differentiation generating myofibroblasts with functional properties consistent with disease promotion. PMID:25596732

  13. Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts.

    PubMed

    Chowdhury, Ridwana; Webber, Jason P; Gurney, Mark; Mason, Malcolm D; Tabi, Zsuzsanna; Clayton, Aled

    2015-01-20

    Stromal fibroblasts become altered in response to solid cancers, to exhibit myofibroblastic characteristics, with disease promoting influence. Infiltrating mesenchymal stem cells (MSC) may contribute towards these changes, but the factors secreted by cancer cells that impact MSC differentiation are poorly understood. We investigated the role of nano-metre sized vesicles (exosomes), secreted by prostate cancer cells, on the differentiation of bone-marrow MSC (BM-MSC), and the subsequent functional consequences of such changes. Purified exosomes impaired classical adipogenic differentiation, skewing differentiation towards alpha-smooth muscle actin (αSMA) positive myofibroblastic cells. A single exosomes treatment generated myofibroblasts secreting high levels of VEGF-A, HGF and matrix regulating factors (MMP-1, -3 and -13). Differentiated MSC had pro-angiogenic functions and enhanced tumour proliferation and invasivity assessed in a 3D co-culture model. Differentiation was dependent on exosomal-TGFβ, but soluble TGFβ at matched dose could not generate the same phenotype. Exosomes present in the cancer cell secretome were the principal factors driving this phenotype. Prostate cancer exosomes dominantly dictate a programme of MSC differentiation generating myofibroblasts with functional properties consistent with disease promotion. PMID:25596732

  14. HBpF-proBDNF: A New Tool for the Analysis of Pro-Brain Derived Neurotrophic Factor Receptor Signaling and Cell Biology

    PubMed Central

    Gaub, Perrine; de Léon, Andrès; Gibon, Julien; Soubannier, Vincent; Dorval, Geneviève; Séguéla, Philippe; Barker, Philip A.

    2016-01-01

    Neurotrophins activate intracellular signaling pathways necessary for neuronal survival, growth and apoptosis. The most abundant neurotrophin in the adult brain, brain-derived neurotrophic factor (BDNF), is first synthesized as a proBDNF precursor and recent studies have demonstrated that proBDNF can be secreted and that it functions as a ligand for a receptor complex containing p75NTR and sortilin. Activation of proBDNF receptors mediates growth cone collapse, reduces synaptic activity, and facilitates developmental apoptosis of motoneurons but the precise signaling cascades have been difficult to discern. To address this, we have engineered, expressed and purified HBpF-proBDNF, an expression construct containing a 6X-HIS tag, a biotin acceptor peptide (BAP) sequence, a PreScission™ Protease cleavage site and a FLAG-tag attached to the N-terminal part of murine proBDNF. Intact HBpF-proBDNF has activities indistinguishable from its wild-type counterpart and can be used to purify proBDNF signaling complexes or to monitor proBDNF endocytosis and retrograde transport. HBpF-proBDNF will be useful for characterizing proBDNF signaling complexes and for deciphering the role of proBDNF in neuronal development, synapse function and neurodegenerative disease. PMID:26950209

  15. HBpF-proBDNF: A New Tool for the Analysis of Pro-Brain Derived Neurotrophic Factor Receptor Signaling and Cell Biology.

    PubMed

    Gaub, Perrine; de Léon, Andrès; Gibon, Julien; Soubannier, Vincent; Dorval, Geneviève; Séguéla, Philippe; Barker, Philip A

    2016-01-01

    Neurotrophins activate intracellular signaling pathways necessary for neuronal survival, growth and apoptosis. The most abundant neurotrophin in the adult brain, brain-derived neurotrophic factor (BDNF), is first synthesized as a proBDNF precursor and recent studies have demonstrated that proBDNF can be secreted and that it functions as a ligand for a receptor complex containing p75NTR and sortilin. Activation of proBDNF receptors mediates growth cone collapse, reduces synaptic activity, and facilitates developmental apoptosis of motoneurons but the precise signaling cascades have been difficult to discern. To address this, we have engineered, expressed and purified HBpF-proBDNF, an expression construct containing a 6X-HIS tag, a biotin acceptor peptide (BAP) sequence, a PreScission™ Protease cleavage site and a FLAG-tag attached to the N-terminal part of murine proBDNF. Intact HBpF-proBDNF has activities indistinguishable from its wild-type counterpart and can be used to purify proBDNF signaling complexes or to monitor proBDNF endocytosis and retrograde transport. HBpF-proBDNF will be useful for characterizing proBDNF signaling complexes and for deciphering the role of proBDNF in neuronal development, synapse function and neurodegenerative disease. PMID:26950209

  16. Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities

    PubMed Central

    Teresa Pinto, Ana; Laranjeiro Pinto, Marta; Patrícia Cardoso, Ana; Monteiro, Cátia; Teixeira Pinto, Marta; Filipe Maia, André; Castro, Patrícia; Figueira, Rita; Monteiro, Armanda; Marques, Margarida; Mareel, Marc; dos Santos, Susana Gomes; Seruca, Raquel; Adolfo Barbosa, Mário; Rocha, Sónia; José Oliveira, Maria

    2016-01-01

    In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2 Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10 Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more pro-inflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy. PMID:26735768

  17. Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This Quick Time movie is of NASA's Propulsive Small Expendable Deployer System experiment (ProSEDS). ProSEDS will demonstrate the use of an electrodynamic tether, basically a long, thin wire, for propulsion. An electrodynamic tether uses the same principles as electric motors in toys, appliances and computer disk drives, and generators in automobiles and power plants. When electrical current is flowing through the tether, a magnetic field is produced that pushes against the magnetic field of the Earth. For ProSEDS, the current in the tether results by virtue of the voltage generated when the tether moves through the Earth's magnetic field at more than 17,000 mph. This approach can produce drag thrust generating useable power. Since electrodynamic tethers require no propellant, they could substantially reduce the weight of the spacecraft and provide a cost-effective method of reboosting spacecraft. The tether would be a 3.1-mile (5 kilometer) long, ultrathin base-wire tether connected with a 6.2-mile (10 kilometer) long nonconducting tether. The ProSEDS experiment is managed by the Space Transportation Directorate at the Marshall Space Flight Center.

  18. 31 CFR 50.93 - Application of pro rata share.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Application of pro rata share. 50.93 Section 50.93 Money and Finance: Treasury Office of the Secretary of the Treasury TERRORISM RISK INSURANCE... from a subsequent act of terrorism....

  19. 19 CFR 122.74 - Incomplete (pro forma) manifest.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.74 Incomplete (pro forma) manifest. (a) Application—(1) Shipments to foreign countries. Except for aircraft bound for foreign locations referred to in paragraph...

  20. 19 CFR 122.74 - Incomplete (pro forma) manifest.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.74 Incomplete (pro forma) manifest. (a) Application—(1) Shipments to foreign countries. Except for aircraft bound for foreign locations referred to in paragraph...

  1. 19 CFR 122.74 - Incomplete (pro forma) manifest.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.74 Incomplete (pro forma) manifest. (a) Application—(1) Shipments to foreign countries. Except for aircraft bound for foreign locations referred to in paragraph...

  2. 19 CFR 122.74 - Incomplete (pro forma) manifest.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...; Electronic Manifest Requirements for Passengers, Crew Members, and Non-Crew Members Onboard Commercial Aircraft Departing From the United States § 122.74 Incomplete (pro forma) manifest. (a) Application—(1) Shipments to foreign countries. Except for aircraft bound for foreign locations referred to in paragraph...

  3. Pro-Forms as Projective Devices in Interaction

    ERIC Educational Resources Information Center

    Keevallik, Leelo

    2011-01-01

    Cataphoric pronouns have been characterized as being co-referential with a word that comes later. Considering that talk is produced in real time, with little benefit of knowing what is yet to come, participants understand cataphoric pro-forms to be projecting more talk. Projection is a crucial interactive resource, as it enables speakers to align…

  4. Mexican American Adolescents' Perceptions of a Pro-College Culture

    ERIC Educational Resources Information Center

    Castillo, Linda G.; Conoley, Collie W.; Cepeda, Lisa M.; Ivy, Karen K.; Archuleta, Debra J.

    2010-01-01

    Three focus groups of ninth-grade Mexican American students explored the factors contributing to a pro-college culture. The students participated in the federal initiative program called "Gaining Early Awareness and Readiness for Undergraduate Programs." Analysis revealed specific student, family, peer, and school personnel influences toward a…

  5. Do Null Subjects (Mis-)Trigger Pro-Drop Grammars?

    ERIC Educational Resources Information Center

    Frazier, Lyn

    2015-01-01

    Native speakers of English regularly hear sentences without overt subjects. Nevertheless, they maintain a [[superscript -]pro] grammar that requires sentences to have an overt subject. It is proposed that listeners of English recognize that speakers reduce predictable material and thus attribute null subjects to this process, rather than changing…

  6. Watts Up? Pro AC Power Meter for Automated Energy Recording

    PubMed Central

    Hirst, Jason M.; Miller, Jonathan R.; Kaplan, Brent A.; Reed, Derek D.

    2013-01-01

    The purpose of the present paper is to review the Watts up? Pro AC power meter. Evaluations of the meter's reliability for measuring energy consumption by consumer electronics yielded acceptable levels of reliability. Implications and limitations for the use of this product in behavior analytic research and practice are discussed.

  7. The Role of Cyclo(His-Pro) in Neurodegeneration.

    PubMed

    Grottelli, Silvia; Ferrari, Ilaria; Pietrini, Grazia; Peirce, Matthew J; Minelli, Alba; Bellezza, Ilaria

    2016-01-01

    Neurodegenerative diseases may have distinct genetic etiologies and pathological manifestations, yet share common cellular mechanisms underpinning neuronal damage and dysfunction. These cellular mechanisms include excitotoxicity, calcium dysregulation, oxidative damage, ER stress and neuroinflammation. Recent data have identified a dual role in these events for glial cells, such as microglia and astrocytes, which are able both to induce and to protect against damage induced by diverse stresses. Cyclo(His-Pro), a cyclic dipeptide derived from the hydrolytic removal of the amino-terminal pyroglutamic acid residue of the hypothalamic thyrotropin-releasing hormone, may be important in regulating the nature of the glial cell contribution. Cyclo(His-Pro) is ubiquitous in the central nervous system and is a key substrate of organic cation transporters, which are strongly linked to neuroprotection. The cyclic dipeptide can also cross the brain-blood-barrier and, once in the brain, can affect diverse inflammatory and stress responses by modifying the Nrf2-NF-κB signaling axis. For these reasons, cyclo(His-Pro) has striking potential for therapeutic application by both parenteral and oral administration routes and may represent an important new tool in counteracting neuroinflammation-based degenerative pathologies. In this review, we discuss the chemistry and biology of cyclo(His-Pro), how it may interact with the biological mechanisms driving neurodegenerative disease, such as amyotrophic lateral sclerosis, and thereby act to preserve or restore neuronal function. PMID:27529240

  8. Memory for Pro-Social Intentions: When Competing Motives Collide

    ERIC Educational Resources Information Center

    Brandimonte, Maria A.; Ferrante, Donatella; Bianco, Carmela; Villani, Maria Grazia

    2010-01-01

    Memory for future actions, or "prospective memory" (PM), often involves remembering to do things "for others". The present article explores the motivational mechanisms underlying memory for pro-social intentions through the manipulation of the social relevance of goals and presence of material rewards during an activity-based PM task. Results…

  9. The Role of Cyclo(His-Pro) in Neurodegeneration

    PubMed Central

    Grottelli, Silvia; Ferrari, Ilaria; Pietrini, Grazia; Peirce, Matthew J.; Minelli, Alba; Bellezza, Ilaria

    2016-01-01

    Neurodegenerative diseases may have distinct genetic etiologies and pathological manifestations, yet share common cellular mechanisms underpinning neuronal damage and dysfunction. These cellular mechanisms include excitotoxicity, calcium dysregulation, oxidative damage, ER stress and neuroinflammation. Recent data have identified a dual role in these events for glial cells, such as microglia and astrocytes, which are able both to induce and to protect against damage induced by diverse stresses. Cyclo(His-Pro), a cyclic dipeptide derived from the hydrolytic removal of the amino-terminal pyroglutamic acid residue of the hypothalamic thyrotropin-releasing hormone, may be important in regulating the nature of the glial cell contribution. Cyclo(His-Pro) is ubiquitous in the central nervous system and is a key substrate of organic cation transporters, which are strongly linked to neuroprotection. The cyclic dipeptide can also cross the brain-blood-barrier and, once in the brain, can affect diverse inflammatory and stress responses by modifying the Nrf2-NF-κB signaling axis. For these reasons, cyclo(His-Pro) has striking potential for therapeutic application by both parenteral and oral administration routes and may represent an important new tool in counteracting neuroinflammation-based degenerative pathologies. In this review, we discuss the chemistry and biology of cyclo(His-Pro), how it may interact with the biological mechanisms driving neurodegenerative disease, such as amyotrophic lateral sclerosis, and thereby act to preserve or restore neuronal function. PMID:27529240

  10. Affordance, Learning Opportunities, and the Lesson Plan Pro Forma

    ERIC Educational Resources Information Center

    Anderson, Jason

    2015-01-01

    This article argues that the most commonly used lesson plan pro formas in language teacher education are inappropriately premised on an outcomes-based approach to teaching, one that is in conflict with what we know about how languages are learnt and how experienced teachers teach. It proposes an alternative, affordance-based approach to lesson…

  11. MEMS Pro Design Kit - Parts A, B, and C

    Energy Science and Technology Software Center (ESTSC)

    2006-06-15

    Part A: SUMMiT V design Kit components for use with MEMS Pro from SoftMEMS Part B: SUMMiT V remote DRC and gear generator source code for use with autocad visual basic Part C: SUMMiT V DRC rules source and test cases for Calibre DRC engine

  12. The "Creation-Science" Case and Pro Bono Publico.

    ERIC Educational Resources Information Center

    Kerr, Peggy L.

    1982-01-01

    Describes contributions and efforts of New York law firm (Skadden, Arps, Slate, Meagher, Flom) personnel in developing plaintiff's case in McLean v. Arkansas 590 (balanced treatment of creationism/evolution). Discusses aspects of "Pro Bono Publico" (unpaid public interest service) endeavors in general and those related to this law firm in…

  13. Affecting Community Change: Involving "Pro Bono" Professionals as Extension Volunteers

    ERIC Educational Resources Information Center

    Kelley, Diane T.; Culp, Ken, III

    2013-01-01

    "Pro bono" volunteers provide an effective means for Extension professionals to expand limited financial and human resources. Volunteers recruited from business settings can provide skills, abilities, expertise, leadership, and resources to Extension programs. Allowing professional volunteers to meet their desired leadership goals while…

  14. Virtex-II Pro SEE Test Methods and Results

    NASA Technical Reports Server (NTRS)

    Petrick, David; Powell, Wesley; Howard, James W., Jr.; LaBel, Kenneth A.

    2004-01-01

    The objective of this coarse Single Event Effect (SEE) test is to determine the suitability of the commercial Virtex-II Pro family for use in spaceflight applications. To this end, this test is primarily intended to determine any Singe Event Latchup (SEL) susceptibilities for these devices. Secondly, this test is intended to measure the level of Single Event Upset (SEU) susceptibilities and in a general sense where they occur. The coarse SEE test was performed on a commercial XC2VP7 device, a relatively small single processor version of the Virtex-II Pro. As the XC2VP7 shares the same functional block design and fabrication process with the larger Virtex-II Pro devices, the results of this test should also be applicable to the larger devices. The XC2VP7 device was tested on a commercial Virtex-II Pro development board. The testing was performed at the Cyclotron laboratories at Texas A&M and Michigan State Universities using ions of varying energy levels and fluences.

  15. Promoting pro-environmental action in climate change deniers

    NASA Astrophysics Data System (ADS)

    Bain, Paul G.; Hornsey, Matthew J.; Bongiorno, Renata; Jeffries, Carla

    2012-08-01

    A sizeable (and growing) proportion of the public in Western democracies deny the existence of anthropogenic climate change. It is commonly assumed that convincing deniers that climate change is real is necessary for them to act pro-environmentally. However, the likelihood of `conversion' using scientific evidence is limited because these attitudes increasingly reflect ideological positions. An alternative approach is to identify outcomes of mitigation efforts that deniers find important. People have strong interests in the welfare of their society, so deniers may act in ways supporting mitigation efforts where they believe these efforts will have positive societal effects. In Study 1, climate change deniers (N=155) intended to act more pro-environmentally where they thought climate change action would create a society where people are more considerate and caring, and where there is greater economic/technological development. Study 2 (N=347) replicated this experimentally, showing that framing climate change action as increasing consideration for others, or improving economic/technological development, led to greater pro-environmental action intentions than a frame emphasizing avoiding the risks of climate change. To motivate deniers' pro-environmental actions, communication should focus on how mitigation efforts can promote a better society, rather than focusing on the reality of climate change and averting its risks.

  16. Intrinsic structural disorder of mouse proNGF.

    PubMed

    Paoletti, Francesca; Covaceuszach, Sonia; Konarev, Peter V; Gonfloni, Stefania; Malerba, Francesca; Schwarz, Elisabeth; Svergun, Dmitri I; Cattaneo, Antonino; Lamba, Doriano

    2009-06-01

    The unprocessed precursor of the Nerve Growth Factor (NGF), proNGF, has additional functions, besides its initially described role as a chaperone for NGF folding. The precursor protein endows apoptotic and/or neurotrophic properties, in contrast to the mature part. The structural and molecular basis for such distinct activities are presently unknown. Aiming to gain insights into the specific molecular interactions that govern rm-proNGF biological activities versus those of its mature counterpart, a structural study by synchrotron small angle X-ray scattering (SAXS) in solution was carried out. The different binding properties of the two proteins were investigated by surface plasmon resonance (SPR) using, as structural probes, a panel of anti-NGF antibodies and the soluble forms of TrkA and p75(NTR) receptors. SAXS measurements revealed the rm-proNGF to be dimeric and anisometric, with the propeptide domain being intrinsically unstructured. Ab initio reconstructions assuming twofold symmetry generated two types of structural models, a globular "crab-like" and an elongated shape that resulted in equally good fits of the scattering data. A novel method accounting for possible coexistence of different conformations contributing to the experimental scattering pattern, with no symmetry constraints, suggests the "crab-like" to be a more likely proNGF conformation. To exploit the potential of chemical stabilizers affecting the existing conformational protein populations, SAXS data were also collected in the presence of ammonium sulphate. An increase of the proNGF compactness was observed. SPR data pinpoints that the propeptide of proNGF may act as an intrinsically unstructured protein domain, characterized by a molecular promiscuity in the interaction/binding to multiple partners (TrkA and p75(NTR) receptors and a panel of neutralizing anti-NGF antibodies) depending on the physiological conditions of the cell. These data provide a first insight into the structural basis

  17. Pro-apoptotic Action of Corticosterone in Hippocampal Organotypic Cultures.

    PubMed

    Kurek, Anna; Kucharczyk, Mateusz; Detka, Jan; Ślusarczyk, Joanna; Trojan, Ewa; Głombik, Katarzyna; Bojarski, Bartosz; Ludwikowska, Agnieszka; Lasoń, Władysław; Budziszewska, Bogusława

    2016-08-01

    Elevated levels of glucocorticoids exert neurotoxic effects, and the hippocampus is particularly sensitive to the effects of glucocorticoids. Because some data have indicated that an increased action of glucocorticoids in the perinatal period enhances the susceptibility of brain tissue to adverse substances later in life, the main purpose of the present study was to compare necrotic/apoptotic corticosterone action in hippocampal organotypic cultures obtained from control animals with the effect of this steroid in tissue from prenatally stressed rats. Because the adverse effects of glucocorticoid action on nerve cell viability appear to result mainly from an increase in the intensity of the effects of glutamate and changes in growth factor and pro-inflammatory cytokine synthesis, the involvement of these factors in corticosterone action were also determined. In stress-like concentration (1 μM), corticosterone, when added to hippocampal cultures for 1 and 3 days, alone or jointly with glutamate, did not induce necrosis. In contrast, in 3-day cultures, corticosterone (1 μM) increased caspase-3 activity and the mRNA expression of the pro-apoptotic Bax. Moreover, corticosterone's effect on caspase-3 activity was stronger in hippocampal cultures from prenatally stressed compared to control rats. Additionally, 24 h of exposure to corticosterone and glutamate, when applied separately and together, increased Bdnf, Ngf, and Tnf-α expression. In contrast, after 72 h, a strong decrease in the expression of both growth factors was observed, while the expression of TNF-α remained high. The present study showed that in stress-like concentrations, corticosterone exerted pro-apoptotic but not necrotic effects in hippocampal organotypic cultures. Prenatal stress increased the pro-apoptotic effects of corticosterone. Increased synthesis of the pro-inflammatory cytokine TNF-α may be connected with the adverse effects of corticosterone on brain cell viability. PMID:27189478

  18. Progastrin a new pro-angiogenic factor in colorectal cancer.

    PubMed

    Najib, S; Kowalski-Chauvel, A; Do, C; Roche, S; Cohen-Jonathan-Moyal, E; Seva, C

    2015-06-11

    Angiogenesis is essential in tumor progression and metastatic process, and increased angiogenesis has been associated with poor prognosis and relapse of colorectal cancer (CRC). VEGF has become the main target of anti-angiogenic therapy. However, most patients relapse after an initial response or present a resistance to the treatment. Identification of new pro-angiogenic factors may help to improve anti-angiogenic therapy. In this study, we demonstrated that the pro-hormone progastrin (PG), over-expressed in CRC, recognized as a growth factor, is a potent pro-angiogenic factor. In transgenic mice and human colorectal HPs producing high levels of PG, we correlated PG overexpression with an increased vascularization. In vitro, exogenous PG and conditioned media (CM) from CRC cells producing PG increased endothelial cell proliferation and migration. We also showed that treatment with exogenous PG can increase the ability of endothelial cells to form capillary-like structures. Moreover, we demonstrated that PG enhanced endothelial permeability. The finding that PG stimulated the phosphorylation of vascular endothelial (VE)-cadherin, p125-FAK, paxillin and induced actin remodelling was consistent with a role of these components in PG-stimulated endothelial cell migration and permeability. The pro-angiogenic effects observed with CM were significantly inhibited when CRC cells expressed a PG shRNA. In vivo, we found an important decrease in tumor growth and neovascularization when the CRC cells expressing the PG shRNA were xenografted in mice or in the chick chorioallantoic membrane model. We also observed an increase in the coverage of blood vessels by pericytes and a decrease in endothelial permeability when PG expression was blocked. Our results demonstrate that PG is a new pro-angiogenic factor in CRC and an attractive therapeutic target. PMID:25109333

  19. Using Pro/ENGINEER`s{reg_sign} interface module

    SciTech Connect

    Schulze, J.

    1994-06-01

    When the ACCORD Process introduced Pro/ENGINEER to Sandians several years ago, a new process for design/definition was implemented. Prior to ACCORD, engineers and draftsmen worked in the 2-D mode with a program caned ANVIL{reg_sign}, which had limited capabilities. Although the transition from 2-D modeling to 3-D modeling met with some resistance, most engineers have embraced this new concept with enthusiasm They are now able to work in the 3-D mode and at increased levels of productivity with appropriate time savings never achieved before. One area that Pro/ENGINEER is noted for that this report will concentrate on, is the powerful interface module with its wide selection of transfer file configurations. This allows the engineer to create parts or assemblies and transfer them to many different second party software packages whose vendors can provide the capability for stress analysis, rapid prototypes, virtual reality environments, or many other forms of advanced manufacturing modes of communication. The ACCORD Program has at its core, the Pro/ENGINEER program from Parametric Technology Inc. Included in the ACCORD program, are several supporting programs from other vendors to make this cooperation between software packages a reality. It is possible to create parts in Pro/ENG transfer those parts to another package that has the capability to analyze the parts for deficiencies, then optimize those parts, and allow for changes to be made. Also included in this report, are other packages closely tied to Pro/ENGINEER, but not necessarily supported under the ACCORD program. Some of these packages allow you to create very impressive video productions, or allow you to meander through a virtual reality scenario. All of these new software packages will give you a new perspective on performance. This report will show how some of these interfaces work, and how you can improve your productivity if you utilize the ACCORD program as it is implemented here at Sandia.

  20. Development of Polymer Coatings for the ProSEDS Tether

    NASA Technical Reports Server (NTRS)

    Vaughn, Jason A.; Kamenetsky, Rachel R.; Finckenor, Miria; Wright, Ken

    2000-01-01

    The ProSEDS mission is designed to provide an on-orbit demonstration of the electrodynamic propulsion capabilities of tethers in space. The ProSEDS experiment will be a secondary payload on a Delta 11 unmanned, expendable booster. A 5 km conductive tether is attached to the deployer baseplate on the Delta 11 second stage and collects current from the low Earth orbit (LEO) plasma to facilitate de-orbit of the Delta II second stage. The conductive tether is attached to a 10-15 km non-conductive tether, which in turn is attached to an endmass. A bare metal tether would have the best conductivity but thermal concerns preclude this design. A conductive polymer developed by Triton Systems has been optimized for optimum conductivity and thermo-optical properties. The current design for the ProSEDS conductive tether is seven individually coated strands of 28 AWG aluminum wire, coated with 12.7 micrometers (0.5 mil) atomic oxygen-resistant conductive polymer composed of a mixture of COR and PANi, wrapped around a braided Kevlar 29 core. Extensive testing has been performed at the Marshall Space Flight Center to qualify this material for flight on ProSEDS. Atomic oxygen exposure has been performed, with solar absorptance and infrared emittance measured before and after exposure. Plasma chamber tests have been completed, as well as tether deployment tests. Also developed for the ProSEDS mission was the insulating polymer TOR-BP. Approximately 200 meters of the conductive tether closest to the Delta II second stage is insulated to prevent any electron reconnection to the tether from the plasma contactor. The insulating material is TOR-BP with a dielectric strength of TBD.

  1. The miR-545/374a cluster encoded in the Ftx lncRNA is overexpressed in HBV-related hepatocellular carcinoma and promotes tumorigenesis and tumor progression.

    PubMed

    Zhao, Qi; Li, Tao; Qi, Jianni; Liu, Juan; Qin, Chengyong

    2014-01-01

    Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Previous studies have shown several long noncoding RNAs (lncRNAs) play various roles in HCC progression, but no research has focused on the expression pattern of microRNA clusters encoded in lncRNAs. The Ftx gene encodes a lncRNA which harbors 2 clusters of microRNAs in its introns, the miR-374b/421 cluster and the miR-545/374a cluster. To date, no research has focused on the role of the miR-545/374a and miR-374b/421 clusters in HBV-related HCC. In this study, 66 pairs of HBV-related HCC tissue and matched non-cancerous liver tissue specimens were analyzed for the expression of the Ftx microRNA clusters. Our results showed that the miR-545/374a cluster was upregulated in HBV-HCC tissue and significantly correlated with prognosis-related clinical features, including histological grade, metastasis and tumor capsule. Transfection studies with microRNA mimics and inhibitors revealed that miR-545/374a expression promoted in vitro cell proliferation, cell migration and invasion. The wild-type HBV-genome-containing plasmid or full-length HBx protein encoding plasmid was transfected into the Bel-7402 cell line and observed for their influence on miR-545/374a expression. We found that transfection of the HBV genome or HBx alone resulted in an increase in miR-545/374a expression. Next, by monitoring the expression of sera miR-545/374a before and after surgical tumor excision, we found serum miR-545/374a was tumor-derived and exhibited a sharp decrease 25 days after tumor excision. We also examined the gender-based difference in miR-545/374a expression among HCC patients and utilized microRNA target prediction software to find the targets of miR-545/374a. One of these targets, namely estrogen-related receptor gamma (ESRRG) was inversely correlated with miR-545 expression. In conclusion, the overexpression of miR-545/374a cluster located in the Ftx lncRNA is partially responsible for a

  2. The miR-545/374a Cluster Encoded in the Ftx lncRNA is Overexpressed in HBV-Related Hepatocellular Carcinoma and Promotes Tumorigenesis and Tumor Progression

    PubMed Central

    Zhao, Qi; Li, Tao; Qi, Jianni; Liu, Juan; Qin, Chengyong

    2014-01-01

    Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Previous studies have shown several long noncoding RNAs (lncRNAs) play various roles in HCC progression, but no research has focused on the expression pattern of microRNA clusters encoded in lncRNAs. The Ftx gene encodes a lncRNA which harbors 2 clusters of microRNAs in its introns, the miR-374b/421 cluster and the miR-545/374a cluster. To date, no research has focused on the role of the miR-545/374a and miR-374b/421 clusters in HBV-related HCC. In this study, 66 pairs of HBV-related HCC tissue and matched non-cancerous liver tissue specimens were analyzed for the expression of the Ftx microRNA clusters. Our results showed that the miR-545/374a cluster was upregulated in HBV-HCC tissue and significantly correlated with prognosis-related clinical features, including histological grade, metastasis and tumor capsule. Transfection studies with microRNA mimics and inhibitors revealed that miR-545/374a expression promoted in vitro cell proliferation, cell migration and invasion. The wild-type HBV-genome-containing plasmid or full-length HBx protein encoding plasmid was transfected into the Bel-7402 cell line and observed for their influence on miR-545/374a expression. We found that transfection of the HBV genome or HBx alone resulted in an increase in miR-545/374a expression. Next, by monitoring the expression of sera miR-545/374a before and after surgical tumor excision, we found serum miR-545/374a was tumor-derived and exhibited a sharp decrease 25 days after tumor excision. We also examined the gender-based difference in miR-545/374a expression among HCC patients and utilized microRNA target prediction software to find the targets of miR-545/374a. One of these targets, namely estrogen-related receptor gamma (ESRRG) was inversely correlated with miR-545 expression. In conclusion, the overexpression of miR-545/374a cluster located in the Ftx lncRNA is partially responsible for a

  3. The 2015-16 Pro-Kid Policy Agenda for California: A Guide to Pro-Kid Policymaking

    ERIC Educational Resources Information Center

    Children Now, 2015

    2015-01-01

    The 2015-16 Pro-Kid Policy Agenda for California is the only comprehensive roadmap at the state level for policymakers, stakeholders, and others who want all children--especially children of color and children from low-income families--to have the opportunity to reach their full potential. A plethora of research shows that investments in quality…

  4. The Effects of Super-Flux (High Performance) Dialyzer on Plasma Glycosylated Pro-B-Type Natriuretic Peptide (proBNP) and Glycosylated N-Terminal proBNP in End-Stage Renal Disease Patients on Dialysis

    PubMed Central

    Nakagawa, Yasuaki; Nishikimi, Toshio; Kuwahara, Koichiro; Yasuno, Shinji; Kinoshita, Hideyuki; Kuwabara, Yoshihiro; Nakao, Kazuhiro; Minami, Takeya; Yamada, Chinatsu; Ueshima, Kenji; Ikeda, Yoshihiro; Okamoto, Hiroyuki; Horii, Kazukiyo; Nagata, Kiyoshi; Kangawa, Kenji; Minamino, Naoto; Nakao, Kazuwa

    2014-01-01

    Background Plasma BNP levels are predictive of prognosis in hemodialysis patients. However, recent studies showed that the current BNP immunoassay cross-reacts with glycosylated proBNP, and the NT-proBNP assay underestimates glycosylated NT-proBNP. In addition, the recently developed high performance dialyzer removes medium-sized molecular solutes such as β2-microgloburin. We therefore investigated the effects of high performance dialysis on measured levels of glycosylated proBNP, glycosylated NT-proBNP and other BNP-related peptides in end-stage renal disease (ESRD) patients on hemodialysis. Method The relationships between clinical parameters and BNP-related molecule were also investigated. We used our newly developed immunoassay to measure plasma total BNP and proBNP in 105 normal subjects and 36 ESRD patients before and after hemodialysis. Plasma NT-proBNP was measured using Elecsys II after treatment with or without deglycosylating enzymes. We also measured plasma ANP and cGMP using radioimmunoassays. Results All the measured BNP-related peptides were significantly higher in ESRD patients than healthy subjects. Total BNP (−38.9%), proBNP (−29.7%), glycoNT-proBNP (−45.5%), nonglycoNT-proBNP (−53.4%), ANP (−50.4%) and cGMP (−72.1%) were all significantly reduced after hemodialysis, and the magnitude of the reduction appeared molecular weight- dependent. Both the proBNP/total BNP and glycoNT-proBNP/nonglycoNT-proBNP ratios were increased after hemodialysis. The former correlated positively with hemodialysis vintage and negatively with systolic blood pressure, while the latter correlated positively with parathyroid hormone levels. Conclusion These results suggest that hemodialysis using super-flux dialyzer removes BNP-related peptides in a nearly molecular weight-dependent manner. The ProBNP/total BNP and glycoNT-proBNP/nonglycoNT-proBNP ratios appear to be influenced by hemodialysis-related parameters in ESRD patients on hemodialysis. PMID:24667631

  5. CD28 family of receptors on T cells in chronic HBV infection: Expression characteristics, clinical significance and correlations with PD-1 blockade

    PubMed Central

    Tang, Zong-Sheng; Hao, You-Hua; Zhang, E-Juan; Xu, Chun-Li; Zhou, Yun; Zheng, Xin; Yang, Dong-Liang

    2016-01-01

    The aim of the present study was to investigate the overall clinical expression characteristics of the cluster of differentiation (CD)28 family receptors [CD28, inducible T-cell co-stimulator, programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 and B- and T-lymphocyte attenuator] on T cells in patients with chronic hepatitis B (CHB), analyze the correlations among these receptors and the clinical parameters, and to investigate the effects of PD-1 blockade on the receptor expression profiles, T-cell function and other biological effects. The expression characteristics of the CD28 family of receptors, the effects of PD-1 blockade on the receptor expression profiles and the levels of interferon (IFN)-γ were investigated in the T cells of patients with CHB. In addition, the transcription factor, T-box 21 (T-bet) and GATA binding protein 3 (GATA-3) mRNA expression levels were investigated in the peripheral blood mononuclear cells (PBMCs) of patients with CHB. The expression levels of the CD28 family receptors in the T cells of patients with CHB demonstrated distinct characteristics, for example levels of PD-1 and CTLA-4 on CD4 T cells and ICOS, PD-1, and BTLA on CD8 T cells were increased in cells from patients with CHB compared with those from the healthy individuals. A significant positive correlation was demonstrated among the serum HBV DNA titers and the levels of PD-1 on CD8+ T cells with the highest expression of PD-1 corresponding to viral levels >106 IU/ml. A significant positive correlation was observed between the serum HBV DNA titers and the expression levels of BTLA on CD8+ T cells with the highest expression of BTLA corresponding to viral levels >106 IU/ml. PD-1 blockade altered the expression profiles of CD28 family receptors in the T cells of patients with CHB, partly enhanced T cell function and increased the ratio of T-bet/GATA-3 mRNA in PBMCs. Thus, CD28 family receptors are potential clinical indicators for the rapid

  6. Evolution of pro-protamine P2 genes in primates.

    PubMed

    Retief, J D; Dixon, G H

    1993-06-01

    Protamines P1 and P2 form a family of small basic peptides that represent the major sperm proteins in placental mammals. In human and mouse protamine P2 is one of the most abundant sperm proteins. The protamine P2 gene codes for a P2 precursor, pro-P2 which is later processed by proteolytic cleavages in its N-terminal region to form the mature P2 protamines. We have used polymerase chain amplification to directly sequence the pro-P2 genes of the five major primate families: red howler (Alouatta seniculus) is a New World monkey (Cebidae); the two macaque species, Macaca mulatta and M. nemistrina are Old World monkeys (Cercopithecidae), the gibbon, Hylobates lar, represents one branch of the apes (Hylobatidae); the orangutan, Pongo pygmaeus, gorilla, Gorilla gorilla and two species of chimpanzee Pan paniscus and Pan troglodytes represent a second ape family (Pongidae). These pro-P2 genes are compared with that of human [Domenjoud, L., Nussbaum, G., Adham, I. M., Greeske, G. & Engel, W. (1990) Genomics 8, 127-133]. The overall size and organization of the genes are conserved within the group. The mean length of pro-P2 is 101 residues, with an increase to 102 in M. nemistrina and a decrease to 99 residues in red howler (A. seniculus). In gorilla and red howler one of two 79-bp tandem repeats that occurs 3' of the gene is deleted. Of the 101 deduced amino acids examined, an amino acid change occurs in one or more primates at 45 positions. Considering only the most recently diverged group, the human/gorilla/chimpanzee clade, this represents a very high mutation rate of 0.99 changes/100 sites in 10(6) years. This rapid mutation rate is characteristic of both members of the protamine gene family, P1 and P2. Consideration of the variable nature of the sequences at the multiple sites of proteolysis during the processing of the pro-P2 indicates either that there are several processing enzymes of differing specificities, or more likely that the folded structure of the pro-P2

  7. Differences in the autocatalytic cleavage of pro-PC2 and pro-PC3 can be attributed to sequences within the propeptide and Asp310 of pro-PC2.

    PubMed Central

    Scougall, K; Taylor, N A; Jermany, J L; Docherty, K; Shennan, K I

    1998-01-01

    PC2 and PC3 are subtilisin-like proteases involved in the maturation of prohormones and proneuropeptides within neuroendocrine cells. They are synthesized as zymogens that undergo autocatalytic maturation within the secretory pathway. Maturation of pro-PC2 is slow (t12 >8 h), exhibits a pH optimum of 5.5 and is dependent on calcium (K0.5 2 mM), while pro-PC3 maturation is relatively rapid (t12 15 min), exhibits a neutral pH optimum and is not calcium dependent. These differences in the rates and optimal conditions for activation of the proteases may contribute to the diversity of products generated by these proteases in different cell types. Although highly similar, there are two major differences between pro-PC2 and pro-PC3: the presence of an aspartate at position 310 in pro-PC2 compared with asparagine at the equivalent position in pro-PC3 (and all other members of the subtilisin family), and the N-terminal propeptides, which exhibit low sequence identity (30%). With a view to establishing the structural features that might be responsible for these differences in the maturation of pro-PC2 and pro-PC3, Asp310 in pro-PC2 was mutated to Asn, and Asn309 in pro-PC3 was mutated to Asp. Chimaeric proteins were also made consisting of the pro-region of PC2 fused to the mature portion of PC3 and the pro-region of PC3 fused to the mature region of PC2. The wild-type and mutant DNA constructs were then transcribed and translated in an in vitro system capable of supporting maturation of pro-PC2 and pro-PC3. The results demonstrated that Asp310 of pro-PC2 is responsible for the acidic pH optimum for maturation. Thus changing Asp310 to Asn shifted the pH optimum for maturation to pH 7.0. However, changing Asn309 of pro-PC3 to Asp had no effect on the optimum pH for maturation of pro-PC3. A chimaeric construct containing the propeptide of pro-PC2 attached to PC3 shifted the pH optimum for maturation from pH 7.0 to 6.0 and slowed down the rate of maturation (t12 >8 h). When

  8. 26 CFR 1.355-4 - Non pro rata distributions, etc.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Non pro rata distributions, etc. 1.355-4 Section... (CONTINUED) INCOME TAXES Effects on Shareholders and Security Holders § 1.355-4 Non pro rata distributions... not (a) the distribution is pro rata with respect to all of the shareholders of the...

  9. 20 CFR 416.1133 - What is a pro rata share of household operating expenses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false What is a pro rata share of household operating expenses. 416.1133 Section 416.1133 Employees' Benefits SOCIAL SECURITY ADMINISTRATION....1133 What is a pro rata share of household operating expenses. (a) General. If you pay your pro...

  10. 24 CFR 266.608 - Mortgage insurance premium: Pro rata refund.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Mortgage insurance premium: Pro... premium: Pro rata refund. If the Contract of Insurance is terminated by payment in full or is terminated... account. In computing the pro rata portion of the annual mortgage insurance premium, the date...

  11. 24 CFR 241.825 - Pro rata refund of insurance premium.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Pro rata refund of insurance... Projects Without a HUD-Insured or HUD-Held Mortgage Premiums § 241.825 Pro rata refund of insurance premium... Commissioner shall refund to the lender for the account of the borrower an amount equal to the pro rata...

  12. 17 CFR 240.14d-8 - Exemption from statutory pro rata requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Exemption from statutory pro... Regulations Under the Securities Exchange Act of 1934 Regulation 14d § 240.14d-8 Exemption from statutory pro rata requirements. Notwithstanding the pro rata provisions of section 14(d)(6) of the Act, if...

  13. 78 FR 49739 - ProLiance Energy, LLC; Notice for Amendment of Petition for Temporary Waivers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-15

    ... Energy Regulatory Commission ProLiance Energy, LLC; Notice for Amendment of Petition for Temporary Waivers Take notice that on August 8, 2013, ProLiance Energy, LLC filed with the Federal Energy Regulatory...\\ \\1\\ ProLiance Energy, LLC, 144 FERC ] 61,037 (2013). Any person desiring to intervene or to...

  14. 24 CFR 203.319 - Pro rata payment of premiums and charges.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Pro rata payment of premiums and... § 203.319 Pro rata payment of premiums and charges. No contract of insurance shall be terminated until the mortgagee has paid to the Commissioner the pro rata portion of the current annual MIP or...

  15. 24 CFR 203.462 - Pro rata payment of premium before termination.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Pro rata payment of premium before... Pro rata payment of premium before termination. No contract of insurance shall be terminated until the lender has paid to the Commissioner the pro rata portion of the current annual insurance premium....

  16. 78 FR 49740 - ProLiance Energy, LLC; Notice for Amendment of Petition for Temporary Waivers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-15

    ... Energy Regulatory Commission ProLiance Energy, LLC; Notice for Amendment of Petition for Temporary Waivers Take notice that on August 9, 2013, ProLiance Energy, LLC filed with the Federal Energy Regulatory...\\ \\1\\ ProLiance Energy, LLC, 144 FERC ] 61,075 (2013). Any person desiring to intervene or to...

  17. 24 CFR 203.319 - Pro rata payment of premiums and charges.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Pro rata payment of premiums and... § 203.319 Pro rata payment of premiums and charges. No contract of insurance shall be terminated until the mortgagee has paid to the Commissioner the pro rata portion of the current annual MIP or...

  18. 24 CFR 241.825 - Pro rata refund of insurance premium.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Pro rata refund of insurance... Projects Without a HUD-Insured or HUD-Held Mortgage Premiums § 241.825 Pro rata refund of insurance premium... Commissioner shall refund to the lender for the account of the borrower an amount equal to the pro rata...

  19. 26 CFR 1.1059(e)-1 - Non-pro rata redemptions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 11 2011-04-01 2011-04-01 false Non-pro rata redemptions. 1.1059(e)-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Special Rules § 1.1059(e)-1 Non-pro rata redemptions. (a) In general... under section 1059(e)(1). For example, if a redemption of stock is not pro rata as to all...

  20. 17 CFR 240.16a-9 - Stock splits, stock dividends, and pro rata rights.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., and pro rata rights. 240.16a-9 Section 240.16a-9 Commodity and Securities Exchanges SECURITIES AND... Government Securities Dealers § 240.16a-9 Stock splits, stock dividends, and pro rata rights. The following... acquisition of rights, such as shareholder or pre-emptive rights, pursuant to a pro rata grant to all...

  1. 24 CFR 203.462 - Pro rata payment of premium before termination.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Pro rata payment of premium before... Pro rata payment of premium before termination. No contract of insurance shall be terminated until the lender has paid to the Commissioner the pro rata portion of the current annual insurance premium....

  2. 26 CFR 1.355-4 - Non pro rata distributions, etc.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 4 2011-04-01 2011-04-01 false Non pro rata distributions, etc. 1.355-4 Section... (CONTINUED) INCOME TAXES Effects on Shareholders and Security Holders § 1.355-4 Non pro rata distributions... not (a) the distribution is pro rata with respect to all of the shareholders of the...

  3. Profiles of serum microRNAs; miR-125b-5p and miR223-3p serve as novel biomarkers for HBV-positive hepatocellular carcinoma.

    PubMed

    Giray, Burcu Gurer; Emekdas, Gurol; Tezcan, Seda; Ulger, Mahmut; Serin, Mehmet Sami; Sezgin, Orhan; Altintas, Engin; Tiftik, Eyup Naci

    2014-07-01

    Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions including cancer. Certain microRNAs (miRNAs) have been shown early diagnostic potential for many types of cancer. The objective of this study was to investigate the potential of certain serum/plasma miRNAs as novel non-invasive biomarkers for early diagnosis of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). For this reason, the expression levels of 24 miRNA (let-7c, miR-92a-3p, 423-5p, 150-5p, 223-3p, 125b-5p, 342-3p, miR-206, 122-5p, 375, 223-5p, 10a-5p, 23b-5p, 99a-5p, 23a-5p, 10a-3p, 122-3p, 125b-1-3p, 23b-3p, 125b-2-3p, 23a-3p, 92a-1-5p, 92a-2-5p, 99a-3p) were analyzed in plasma of patients with chronic hepatitis B, HBV-positive cirrhosis and HBV-positive HCC and compared with control group samples. Totally 94 plasma samples; 28 control and 66 patient plasma (24 CHB, 22 HBV-positive cirrhosis, 20 HBV-positive HCC) and were included in this study. The expression levels of 24 miRNAs were detected for all control and patient group plasma samples by qRT-PCR using BioMark™ 96.96 Dynamic Array (Fluidigm Corporation) system. The expression levels of miR-125b-5p were detected 2.85 fold, 2.46 fold and 1.89 fold (p = 0.01513, p = 0.0009440, p = 0.0001446) up regulated in CHB, HBV-positive cirrhosis and HBV-positive HCC, respectively when compared versus control group individually by Mann-Whitney U test. The expression levels of miR-223-3p were detected 5.55 fold, 13.88 fold and 12.65 fold (p = 0.01513, p = 0.0009440, p = 0.0001446) down regulated in same comparisons. When all groups were compared versus control group by one-way ANOVA test, the expression levels of miR-223-3p were also found statistically significant (p < 0.05). Although not statistically significant, miR-125b-5p tended to be upregulated. (p = 0.07192). These results significantly imply that miR-125b-5p and miR223-3p could be used as novel non-invasive biomarkers of HBV-positive HCC

  4. IUE observations of proto-planetary and variable planetary nebulae. I - V1016 Cygni, HM Sagittae, and HBV 475. II - A search for variability in IC 4997 and NGC 6905

    NASA Technical Reports Server (NTRS)

    Feibelman, W. A.

    1982-01-01

    The IUE satellite has undertaken UV observations of the proto-planetary nebulae V1016 Cyg, HM Sge, and HBV 475, yielding emission line fluxes, line ratios, line profiles, electron densities, and distances from these objects. While levels of increasing excitation and ionization as a function of time are shown by the data for the first two nebulae, the trend for HBV 475 is found to lead in the opposite direction. The formation of a shell is suggested by dramatic changes in the HM Sge UV line profiles over the last four years, including the disappearance of W-R features and the incipient splitting of the semi-forbidden C III 1909 A line. An additional IUE search for UV variability in the planetary nebulae IC 4997 and NGC 6905 has yielded emission line fluxes, line ratios and profiles, and central star temperatures, as well as stratification effects data for several ions in NGC 6905

  5. Solution structures of active and inactive forms of the DP IV (CD26) inhibitor Pro-boroPro determined by NMR spectroscopy.

    PubMed

    Sudmeier, J L; Günther, U L; Gutheil, W G; Coutts, S J; Snow, R J; Barton, R W; Bachovchin, W W

    1994-10-18

    Synthesis of the boronic acid analog of the dipeptide Pro-Pro yields a mixture of diastereomers Pro-L-boroPro and Pro-D-boroPro, one of which is a potent inhibitor [Ki = 16 pM; Gutheil, W. G., & Bachovchin, W. W. (1993) Biochemistry 32, 8723-8731] of dipeptidyl amino peptidase type IV (DP IV), also known as CD26. The structures of both diasteremers are determined here in aqueous solution by means of 1D and 2D NMR of 1H, 13C, and 11B, and force-field calculations, and the inhibitor is proven to have the L-L configuration. At low pH values (approximately 2), both diastereomers are trans with respect to the peptide bond. Populations of proline ring conformers are determined by pseudorotation analysis, using vicinal proton spin-coupling constants obtained by computer analysis of 1D1H NMR spectral fine structure. At neutral pH values, the Pro-boroPro inhibitor of DP IV undergoes slow, reversible inactivation (Gutheil & Bachovchin, 1993). By structural determination of the decomposition products of both diasteromers, the process is shown here to involve formation of a six-membered ring between the residues by means of trans-cis conversion and formation of a B-N bond, producing chiral nitrogen atoms in both cases having the S configuration. Analogy to cyclic dipeptides suggests the new compounds be named cyclo(Pro-L-boroPro) and cyclo(Pro-D-boroPro). PMID:7918465

  6. Risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen negative/hepatitis B core antibody positive patients receiving rituximab-containing combination chemotherapy without routine antiviral prophylaxis.

    PubMed

    Koo, Yu Xuan; Tay, Matthew; Teh, Yii Ean; Teng, David; Tan, Daniel S W; Tan, Iain B H; Tai, David W M; Quek, Richard; Tao, Miriam; Lim, Soon Thye

    2011-10-01

    The use of rituximab has been associated with increased risk of hepatitis B virus (HBV) reactivation in patients who are hepatitis B surface antigen (HBsAg) negative and antihepatitis B core antibody (anti-HBc) positive. We aim to determine the rate of HBV reactivation in this group of patients who received rituximab-containing combination chemotherapy without concomitant antiviral prophylaxis and to identify potential risk factors for reactivation. Sixty-two HBsAg negative/anti-HBc positive patients with B-cell lymphoma treated with rituximab-based immunochemotherapy from 2006 to 2009 were included. None of the patients received concomitant antiviral prophylaxis. In this cohort, 48 (77%) patients received rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), eight (13%) received rituximab with cyclophosphamide, vincristine and prednisolone, and six (10%) received other chemotherapy regimens. Two patients suffered HBV reactivation; both were above 70 years of age, received R-CHOP chemotherapy and were negative for antihepatitis B surface antibody (anti-HBs) at baseline. One of the two patients reactivated shortly after completion of R-CHOP chemotherapy while the other reactivated during rituximab maintenance treatment. Thus, the overall reactivation rate in this cohort of patients is 3% (2/62), 4% (2/48), and 25% (1/4) in patients who received R-CHOP chemotherapy and who received rituximab maintenance, respectively. The rate of HBV reactivation is low in patients who are HBsAg negative/anti-HBc positive receiving rituximab-based combination chemotherapy without concomitant antiviral prophylaxis. However, elderly patients, particularly those without anti-HBs, seemed particularly at risk. PMID:21520001

  7. Psychological antecedents of heterosexuals' pro-gay activism behavior.

    PubMed

    Wilkinson, Wayne W; Sagarin, Brad J

    2010-01-01

    Previous research on heterosexuals' attitudes toward gays is characterized by a focus on negative attitudes and minimal use of behavioral dependent variables. In an attempt to rectify this situation, the present study explored the psychological antecedents of heterosexuals' pro-gay activism behavior in an undergraduate sample using the theory of planned behavior (Ajzen, 1991). Findings suggest that intentions predict activism behavior (in the form of signing an online petition supporting the construction of a new lesbian, gay, and bisexual resource center on their campus). In addition, attitudes toward the possible outcomes of the behavior, attitudes toward the behavior itself, and self-identity were found to predict intentions. Directions for future research on pro-gay activism are discussed. PMID:20665329

  8. Online Stigma Resistance in the Pro-Ana Community.

    PubMed

    Yeshua-Katz, Daphna

    2015-10-01

    Media scholars often use concepts from Goffman's dramaturgical approach to study online communities of stigmatized individuals as "backstages," spaces where members take refuge from social disapproval. In this study, I extend this view through an examination of in-depth interviews with bloggers from the "pro-ana" community, an online community for people with eating disorders. To explore how this community uses an online environment that is both anonymous and public, I fuse Goffman's ideas about identity performance and stigma with more recent theories about boundary maintenance. In-depth interviews with "pro-ana" bloggers reveal that to protect this virtual group and resist stigmas associated both with their illness and with their online presence, they construct their own norms and rules in the online realm, and discipline and eject members deemed to be out-group. PMID:25667161

  9. Identifying Parents Who Are Amenable to Pro-Vaccination Conversations

    PubMed Central

    Brunson, Emily K.

    2015-01-01

    While health care providers are often cited as parents’ most trusted source for information and advice about vaccination, parents differ in their level of receptiveness to pro-vaccination conversations. The purpose of this research was to identify points in individual parents’ decision-making processes when parents are particularly open to receiving information and advice from their children’s health care providers. Interview data were collected from 20 mothers and 5 couples. Analysis of these data suggested 3 primary circumstances when parents were particularly open to receiving information and advice: during parents’ initial decision-making, as parents continued to assess vaccination options, and during particular circumstances that prompted parents to reconsider previously made vaccination choices. These results provide a mechanism for providers to identify parents who may be particularly receptive to pro-vaccination conversations. By prioritizing conversations with parents at one of these points, health care providers’ efforts at promoting vaccination may be more effective. PMID:27335987

  10. The PACA Project : Pro-Am Collaborative Astronomy

    NASA Astrophysics Data System (ADS)

    Yanamandra-Fisher, P. A.

    2014-04-01

    The Pro-Am Collaborative Astronomy (PACA) project is the next stage of evolution of the paradigm developed for the observational campaign of C/2012 S1 or C/ISON. Four different phases of collaboration are identified, and illustrate the integration of scientific investigations with amateur astronomer community via observations, and models; and the rapid dissemination of the results via a multitude of social media for rapid global access. The success of the paradigm shift in scientific research is now implemented in other comet observing campaigns. Both communities (scientific and amateur astronomers) benefit from these collective, collaborative partnerships; while outreach is the instantaneous deliverable that provides both a framework for future data analyses and the dissemination of the results. While PACA identifies a collaborative approach to pro-am collaborations, given the volume of data generated for each campaign, new ways of rapid data analysis, mining access and storage are needed.

  11. Erratum to: The prevalence of HIV, HBV, HCV, and HIV-related risk-taking behaviors among Palestinian injecting drug users in the East Jerusalem Governorate.

    PubMed

    Stulhofer, Aleksandar; Chetty, Agnes; Rabie, Randa Abu; Jwehan, Isam; Ramlawi, Asad

    2012-08-01

    The objective of the study was to determine HIV, HBV, HCV seroprevalence and to assess HIV risks among Palestinian injecting drug users (IDUs) in the East Jerusalem Governorate. Following formative research, a bio-behavioral survey using respondent-driven sampling was carried out in 2010 among 199 IDUs aged 19-56 years (M = 41.33, SD = 8.09). Venous blood was drawn for biological testing. Data on drug abuse and sexual behaviors were collected by face-to-face interviewing. No HIV + cases were found. Five participants were infected with Hepatitis B and 84 participants (estimated population proportion of 40.3%) tested positive for Hepatitis C. A great majority of the surveyed IDUs (90.4%) reported using sterile injecting equipment the last time they injected. In a multivariate assessment, age (OR = 2.52, p < .05), education (OR = 6.67, p < .01), personal network size (OR = .18, p < .001), and the frequency of drug injecting in the past month (OR = .20, p < .001) were associated with using sterile injecting equipment in the past week. Condom use at most recent sexual intercourse was reported by about a third (34.2%) of IDUs. The study documented substantial exposure to HIV risks among Palestinian IDUs whose vulnerability is inseparable from sociopolitic and socioeconomic characteristics of their social environment. PMID:22782840

  12. The prevalence of HIV, HBV, HCV, and HIV-related risk-taking behaviors among Palestinian injecting drug users in the East Jerusalem Governorate.

    PubMed

    Stulhofer, Aleksandar; Chetty, Agnes; Rabie, Randa Abu; Jwehan, Isam; Ramlawi, Asad

    2012-08-01

    The objective of the study was to determine HIV, HBV, HCV seroprevalence and to assess HIV risks among Palestinian injecting drug users (IDUs) in the East Jerusalem Governorate. Following formative research, a bio-behavioral survey using respondent-driven sampling was carried out in 2010 among 199 IDUs aged 19-56 years(M=41.33, SD=8.09). Venous blood was drawn for biological testing. Data on drug abuse and sexual behaviors were collected by face-to-face interviewing. No HIV+cases were found. Five participants were infected with Hepatitis B and 84 participants(estimated population proportion of 40.3 %) tested positive for Hepatitis C. A great majority of the surveyed IDUs (90.4 %) reported using sterile injecting equipment the last time they injected. In a multivariate assessment, age (OR=2.52, pG.05), education(OR=6.67, pG.01), personal network size (OR=.18, pG.001), and the frequency of drug injecting in the past month (OR=.20, pG.001) were associated with using sterile injecting equipment in the past week. Condom use at most recent sexual intercourse was reported by about a third (34.2 %) of IDUs. The study documented substantial exposure to HIV risks among Palestinian IDUs whose vulnerability is inseparable from sociopolitic and socioeconomic characteristics of their social environment [corrected]. PMID:22674463

  13. Astataricusones A-D and astataricusol A, five new anti-HBV shionane-type triterpenes from Aster tataricus L. f.

    PubMed

    Zhou, Wen-Bing; Zeng, Guang-Zhi; Xu, Hui-Min; He, Wen-Jun; Tan, Ning-Hua

    2013-01-01

    Five new shionane-type triterpenes, astataricusones A-D (compounds 1-4) and astataricusol A (5), together with one known shionane-type triterpene 6 were obtained from the roots and rhizomes of Aster tataricus L. f. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configurations of 1 and 4 was determined by single crystal X-ray diffraction and CD analysis. Compound 2 showed inhibitory activity on HBsAg secretion with an IC50 value of 23.5 μM, while 2 and 6 showed inhibitory activities on HBeAg secretion with IC50 values of 18.6 and 40.5 μM, and cytotoxicity on HepG 2.2.15 cells with CC50 values of 172.4 and 137.7 μM, respectively. Compounds 2 and 6 also exhibited inhibitory activities on HBV DNA replication with IC50 values of 2.7 and 30.7 μM, respectively. PMID:24287992

  14. Cerebral Lateralization of Pro- and Anti-Social Tendencies

    PubMed Central

    2014-01-01

    Mounting evidence suggest that the right-hemisphere (RH) has a relative advantage, over the left-hemisphere (LH), in mediating social intelligence - identifying social stimuli, understanding the intentions of other people, awareness of the dynamics in social relationships, and successful handling of social interactions. Furthermore, a review and synthesis of the literature suggest that pro-social attitudes and behaviors are associated with physiological activity in the RH, whereas unsocial and anti-social tendencies are mediated primarily by the LH. This hemispheric asymmetry is rooted in several neurobiological and functional differences between the two hemispheres. (I) Positive social interactions often require inhibiting one's immediate desires and considering the perspectives and needs of others. Given that self-control is mediated by the RH, pro-social emotions and behaviors are, therefore, inherently associated with the RH as it subserves the brain's self-restraint mechanisms. (II) The RH mediates experiences of vulnerability. It registers the relative clumsiness and motor weakness of the left limbs, and it is involved, more than the LH, in processing threats and mediating fear. Emotional states of vulnerability trigger the need for affiliation and sociality, therefore the RH has a greater role in mediating pro-social attitudes and behaviors. (III) The RH mediates a holistic mode of representing the world. Holistic perception emphasizes similarities rather than differences, takes a long-term perspective, is associated with divergent thinking and seeing other points-of-view, and it mediates a personal mode of relating to people. All these features of holistic perception facilitate a more empathetic attitude toward others and pro-social behaviors. PMID:24737936

  15. The Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    Lorenzini, Enrico C.; Cosmo, Mario L.; Curtis, Leslie (Technical Monitor)

    2003-01-01

    The summary of activity during this reporting period, most of which was covered by a no-cost extension of the grant, is as follows: 1) Participation in remote and in-situ (at MSFC EDAC facility) mission operation simulations; 2) Analysis of the decay rate of ProSEDS when starting the mission at a lower altitude; 3) Analysis of the deployment control law performance when deploying at a lower altitude.

  16. Cervical arthroplasty using ProDisc-C case report.

    PubMed

    Nica, D A; Copaciu, R

    2013-03-15

    Cervical disc replacement is an emerging motion-preserving technology in the surgical treatment of the cervical degenerative disc disorders used as an alternative to the classic interbody fusion. We present a case report of a patient diagnosed with C6-7 right disc herniation who underwent anterior discectomy and received a total disc replacement using ProDisc C artificial disc prosthesis. PMID:23599830

  17. The ProDisc artificial disc: insertion technique.

    PubMed

    Aryan, Henry E; Acosta, Frank L; Ames, Christopher P

    2005-10-01

    The ProDisc artificial lumbar disc was designed for use in treatment of degenerative lumbar disease. The disc is implanted using an anterior approach to the lumbar spine with the assistance of intraoperative fluoroscopy. A variety of insertion instruments guide the surgeon through this process. The disc is implanted via an anterior approach, generally retroperitoneally but on occasion transperitoneally. The different approaches and insertion technique are described in this article. PMID:16326288

  18. Cavum Septum Pellucidum in Retired American Pro-Football Players.

    PubMed

    Gardner, Raquel C; Hess, Christopher P; Brus-Ramer, Marcel; Possin, Katherine L; Cohn-Sheehy, Brendan I; Kramer, Joel H; Berger, Mitchel S; Yaffe, Kristine; Miller, Bruce; Rabinovici, Gil D

    2016-01-01

    Previous studies report that cavum septum pellucidum (CSP) is frequent among athletes with a history of repeated traumatic brain injury (TBI), such as boxers. Few studies of CSP in athletes, however, have assessed detailed features of the septum pellucidum in a case-control fashion. This is important because prevalence of CSP in the general population varies widely (2% to 85%) between studies. Further, rates of CSP among American pro-football players have not been described previously. We sought to characterize MRI features of the septum pellucidum in a series of retired pro-football players with a history of repeated concussive/subconcussive head traumas compared with controls. We retrospectively assessed retired American pro-football players presenting to our memory clinic with cognitive/behavioral symptoms in whom structural MRI was available with slice thickness ≤2 mm (n=17). Each player was matched to a memory clinic control patient with no history of TBI. Scans were interpreted by raters blinded to clinical information and TBI/football history, who measured CSP grade (0-absent, 1-equivocal, 2-mild, 3-moderate, 4-severe) and length according to a standard protocol. Sixteen of 17 (94%) players had a CSP graded ≥2 compared with 3 of 17 (18%) controls. CSP was significantly higher grade (p<0.001) and longer in players than controls (mean length±standard deviation: 10.6 mm±5.4 vs. 1.1 mm±1.3, p<0.001). Among patients presenting to a memory clinic, long high-grade CSP was more frequent in retired pro-football players compared with patients without a history of TBI. PMID:25970145

  19. The Pro-inflammatory Effects of Glucocorticoids in the Brain

    PubMed Central

    Duque, Erica de Almeida; Munhoz, Carolina Demarchi

    2016-01-01

    Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein–protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. PMID:27445981

  20. The Pro-inflammatory Effects of Glucocorticoids in the Brain.

    PubMed

    Duque, Erica de Almeida; Munhoz, Carolina Demarchi

    2016-01-01

    Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein-protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. PMID:27445981

  1. Control of the Immune Response by Pro-Angiogenic Factors

    PubMed Central

    Voron, Thibault; Marcheteau, Elie; Pernot, Simon; Colussi, Orianne; Tartour, Eric; Taieb, Julien; Terme, Magali

    2014-01-01

    The progressive conversion of normal cells into cancer cells is characterized by the acquisition of eight hallmarks. Among these criteria, the capability of the cancer cell to avoid the immune destruction has been noted. Thus, tumors develop mechanisms to become invisible to the immune system, such as the induction of immunosuppressive cells, which are able to inhibit the development of an efficient immune response. Molecules produced in the tumor microenvironment are involved in the occurrence of an immunosuppressive microenvironment. Recently, it has been shown that vascular endothelial growth factor A (VEGF-A) exhibits immunosuppressive properties in addition to its pro-angiogenic activities. VEGF-A can induce the accumulation of immature dendritic cells, myeloid-derived suppressor cells, regulatory T cells, and inhibit the migration of T lymphocytes to the tumor. Other pro-angiogenic factors such as placental growth factor (PlGF) could also participate in tumor-induced immunosuppression, but only few works have been performed on this point. Here, we review the impact of pro-angiogenic factors (especially VEGF-A) on immune cells. Anti-angiogenic molecules, which target VEGF-A/VEGFR axis, have been developed in the last decades and are commonly used to treat cancer patients. These drugs have anti-angiogenic properties but can also counteract the tumor-induced immunosuppression. Based on these immunomodulatory properties, anti-angiogenic molecules could be efficiently associated with immunotherapeutic strategies in preclinical models. These combinations are currently under investigation in cancer patients. PMID:24765614

  2. Virtex-II Pro SEE Test Methods and Results

    NASA Technical Reports Server (NTRS)

    Petrick, David; Powell, Wesley; Howard, James

    2004-01-01

    The Xilinx Virtex-II Pro is a platform FPGA that embeds multiple microprocessors within the fabric of an SRAM-based reprogrammable FPGA. The variety and quantity of resources provided by this family of devices make them very attractive for spaceflight applications. However, these devices will be susceptible to single event effects (SEE), which must be mitigated. To use the Virtex-II Pro reliably in space applications, these devices must first be tested to determine if they are susceptible to single event latchup (SEL), the degree to which they are susceptible to single event upsets (SEU) and single event transients (SET), and how these effects are manifested in the device. With this information, mitigations schemes can be developed and tested that address the specific susceptiblities of these devices. This initial SEE test uses a commercial off the shelf Virtex-II Pro evaluation board, with a single processor XC2VP7 FPGA. The FPGA on this board is an acid etched device, which can be partially covered with a shield. The shield covers a portion of the logic, routing, and memory resources along with some of the RocketIO transceivers. The processor, along with a large portion of logic, routing, memory, and transceivers are left exposed. This test will be performed at the Cyclotron Laboratories at Texas A&M University and Michigan State University using ions of varying energy levels and fluencies.

  3. ProTherm: Thermodynamic Database for Proteins and Mutants.

    PubMed

    Gromiha, M M; An, J; Kono, H; Oobatake, M; Uedaira, H; Sarai, A

    1999-01-01

    The first release of the Thermodynamic Database for Proteins and Mutants (ProTherm) contains more than 3300 data of several thermodynamic parameters for wild type and mutant proteins. Each entry includes numerical data for unfolding Gibbs free energy change, enthalpy change, heat capacity change, transition temperature, activity etc., which are important for understanding the mechanism of protein stability. ProTherm also includes structural information such as secondary structure and solvent accessibility of wild type residues, and experimental methods and other conditions. A WWW interface enables users to search data based on various conditions with different sorting options for outputs. Further, ProTherm is cross-linked with NCBI PUBMED literature database, Protein Mutant Database, Enzyme Code and Protein Data Bank structural database. Moreover, all the mutation sites associated with each PDB structure are automatically mapped and can be directly viewed through 3DinSight developed in our laboratory. The database is available at the URL, http://www.rtc.riken.go.jp/protherm.htm l PMID:9847203

  4. The tetrapeptide N-acetyl-Pro-Pro-Tyr-Leu in skin care formulations-Physicochemical and release studies.

    PubMed

    Olejnik, Anna; Schroeder, Grzegorz; Nowak, Izabela

    2015-08-15

    Recently there has been a growth of interest in the novel skin care formulations containing active ingredients such as low molecular weight peptides. In this paper we present new skincare formulations such as hydrogels, oil-in-water emulsions and water-in-oil emulsion containing a tetrapeptide (N-acetyl-Pro-Pro-Tyr-Leu). These formulations were characterized in terms of physicochemical parameters (pH, viscosity), stability and particle size distribution. Additionally, the diffusion parameters of the peptide in the obtained formulations were calculated based on the Einstein-Smoluchowski equation. Furthermore, in order to determine the penetration of the tetrapeptide through membranes its release kinetics were investigated. On the basis of release curves, the release rate constants were determined. The results proved that the properties of the formulations strongly determined the release rate of the tetrapeptide. The higher viscosity of the semisolid, the slower was the permeation through the membrane. PMID:26188319

  5. Potato virus Y HC-Pro Reduces the ATPase Activity of NtMinD, Which Results in Enlarged Chloroplasts in HC-Pro Transgenic Tobacco.

    PubMed

    Tu, Yayi; Zhang, Zhenqian; Li, Daofeng; Li, Heng; Dong, Jiangli; Wang, Tao

    2015-01-01

    Potato virus Y (PVY) is an important plant virus and causes great losses every year. Viral infection often leads to abnormal chloroplasts. The first step of chloroplast division is the formation of FtsZ ring (Z-ring), and the placement of Z-ring is coordinated by the Min system in both bacteria and plants. In our lab, the helper-component proteinase (HC-Pro) of PVY was previously found to interact with the chloroplast division protein NtMinD through a yeast two-hybrid screening assay and a bimolecular fluorescence complementation (BiFC) assay in vivo. Here, we further investigated the biological significance of the NtMinD/HC-Pro interaction. We purified the NtMinD and HC-Pro proteins using a prokaryotic protein purification system and tested the effect of HC-Pro on the ATPase activity of NtMinD in vitro. We found that the ATPase activity of NtMinD was reduced in the presence of HC-Pro. In addition, another important chloroplast division related protein, NtMinE, was cloned from the cDNA of Nicotiana tabacum. And the NtMinD/NtMinE interaction site was mapped to the C-terminus of NtMinD, which overlaps the NtMinD/HC-Pro interaction site. Yeast three-hybrid assay demonstrated that HC-Pro competes with NtMinE for binding to NtMinD. HC-Pro was previously reported to accumulate in the chloroplasts of PVY-infected tobacco and we confirmed this result in our present work. The NtMinD/NtMinE interaction is very important in the regulation of chloroplast division. To demonstrate the influence of HC-Pro on chloroplast division, we generated HC-Pro transgenic tobacco with a transit peptide to retarget HC-Pro to the chloroplasts. The HC-Pro transgenic plants showed enlarged chloroplasts. Our present study demonstrated that the interaction between HC-Pro and NtMinD interfered with the function of NtMinD in chloroplast division, which results in enlarged chloroplasts in HC-Pro transgenic tobacco. The HC-Pro/NtMinD interaction may cause the formation of abnormal chloroplasts in PVY

  6. Context of action of Proline Dehydrogenase (ProDH) in the Hypersensitive Response of Arabidopsis

    PubMed Central

    2014-01-01

    Background Proline (Pro) dehydrogenase (ProDH) potentiates the oxidative burst and cell death of the plant Hypersensitive Response (HR) by mechanisms not yet elucidated. ProDH converts Pro into ∆1 pyrroline-5-carboxylate (P5C) and can act together with P5C dehydrogenase (P5CDH) to produce Glu, or with P5C reductase (P5CR) to regenerate Pro and thus stimulate the Pro/P5C cycle. To better understand the effects of ProDH in HR, we studied the enzyme at three stages of the defense response differing in their ROS and cell death levels. In addition, we tested if ProDH requires P5CDH to potentiate HR. Results Control and infected leaves of wild type and p5cdh plants were used to monitor ProDH activity, in vivo Pro catabolism, amino acid content, and gene expression. Wild type plants activated ProDH at all HR stages. They did not consume Pro during maximal ROS accumulation, and maintained almost basal P5C levels at all conditions. p5cdh mutants activated ProDH as wild type plants. They achieved maximum oxidative burst and cell death levels producing normal HR lesions, but evidenced premature defense activation. Conclusion ProDH activation has different effects on HR. Before the oxidative burst it leads to Pro consumption involving the action of P5CDH. During the oxidative burst, ProDH becomes functionally uncoupled to P5CDH and apparently works with P5CR. The absence of P5CDH does not reduce ROS, cell death, or pathogen resistance, indicating this enzyme is not accompanying ProDH in the potentiation of these defense responses. In contrast, p5cdh infected plants displayed increased ROS burst and earlier initiation of HR cell death. In turn, our results suggest that ProDH may sustain HR by participating in the Pro/P5C cycle, whose action on HR must be formally evaluated in a future. PMID:24410747

  7. Making Women the Subjects of the Abortion Debate: A Class Exercise that Moves beyond "Pro-Choice" and "Pro-Life"

    ERIC Educational Resources Information Center

    Crawley, Sara L.; Willman, Rebecca K.; Clark, Leisa; Walsh, Clare

    2009-01-01

    In this article, the authors describe a classroom exercise designed to put women (and children and men) back at the center of the abortion debate, avoiding the standard rhetoric and engaging reflection on how everyone might find common political goals among the so-called pro-life and pro-choice sides. The exercise the authors offer in this article…

  8. Removing N-terminal sequences in pre-S1 domain enhanced antibody and B-cell responses by an HBV large surface antigen DNA vaccine.

    PubMed

    Ge, Guohong; Wang, Shixia; Han, Yaping; Zhang, Chunhua; Lu, Shan; Huang, Zuhu

    2012-01-01

    Although the use of recombinant hepatitis B virus surface (HBsAg) protein vaccine has successfully reduced global hepatitis B infection, there are still a number of vaccine recipients who do not develop detectable antibody responses. Various novel vaccination approaches, including DNA vaccines, have been used to further improve the coverage of vaccine protection. Our previous studies demonstrated that HBsAg-based DNA vaccines could induce both humoral and CMI responses in experimental animal models. However, one form of the the HBsAg antigen, the large S antigen (HBs-L), expressed by DNA vaccine, was not sufficiently immunogenic in eliciting antibody responses. In the current study, we produced a modified large S antigen DNA vaccine, HBs-L(T), which has a truncated N-terminal sequence in the pre-S1 region. Compared to the original HBs-L DNA vaccine, the HBs-L(T) DNA vaccine improved secretion in cultured mammalian cells and generated significantly enhanced HBsAg-specific antibody and B cell responses. Furthermore, this improved HBsL DNA vaccine, along with other HBsAg-expressing DNA vaccines, was able to maintain predominantly Th1 type antibody responses while recombinant HBsAg protein vaccines produced in either yeast or CHO cells elicited mostly Th2 type antibody responses. Our data indicate that HBsAg DNA vaccines with improved immunogenicity offer a useful alternative choice to recombinant protein-based HBV vaccines, particularly for therapeutic purposes against chronic hepatitis infection where immune tolerance led to poor antibody responses to S antigens. PMID:22844502

  9. Prevalence of HCV Infections and Co-Infection With HBV and HIV and Associated Risk Factors Among Addicts in Drug Treatment Centers, Lorestan Province, Iran

    PubMed Central

    Norouzian, Hossein; Gholami, Mohammadreza; Shakib, Pegah; Goudarzi, Gholamreza; Ghobadian Diali, Hamze; Rezvani, Azam

    2016-01-01

    Background: Hepatitis C is an infectious disease caused by blood-borne pathogen, hepatitis C virus (HCV). Objectives: The purpose of this study was to investigate the prevalence of HCV infection and associated risk factors among addicts in drug treatment centers in Lorestan Province, Iran. Patients and Methods: A cross-sectional sero-behavioral survey was given to drug addicts in the drug treatment centers of Khorramabad, Lorestan Province, Iran during June 2012 - March 2013. Drug addicts were interviewed using a standard questionnaire including demographic, imprisonment history, and HCV-related risk behavior items. Thereafter, the sera drawn from the participants were tested for anti-HCV antibody (Ab), anti-human immunodeficiency virus (HIV) Ab, and hepatitis B surface antigen (HBsAg). Results: The mean age of the cohorts was 31.7. Up to 60.2% of drug users had educational levels less than high school, 67.5% were self-employed, and 32.5% were office workers. The mean duration of drug injection was 6.8 years. Statistical analyses indicated that the prevalence of HCV among drug addicts was positively associated with age, past incarceration, drug injection history, the duration of drug use, and tattooing. In addition, 16.23% of volunteers were HCV-positive. Of those infected with HCV, 1.10% was co-infected with HBV, 2.95% were positive for HIV, and 0.36% of HCV-positive cases were infected with all three viruses. Conclusions: The high prevalence of HCV infection among this group implies a high rate of transmission and exposure to the risk of serious diseases. It is important that the high prevalence of HCV infection be taken into consideration to control further transmission of this infection. PMID:27162762

  10. Capturing Patient-Reported Outcome (PRO) Data Electronically: The Past, Present, and Promise of ePRO Measurement in Clinical Trials.

    PubMed

    Coons, Stephen Joel; Eremenco, Sonya; Lundy, J Jason; O'Donohoe, Paul; O'Gorman, Hannah; Malizia, William

    2015-08-01

    Patient-reported outcomes (PROs) are an important means of evaluating the treatment benefit of new medical products. It is recognized that PRO measures should be used when assessing concepts best known by the patient or best measured from the patient's perspective. As a result, there is growing emphasis on well defined and reliable PRO measures. In addition, advances in technology have significantly increased electronic PRO (ePRO) data collection capabilities and options in clinical trials. The movement from paper-based to ePRO data capture has enhanced the integrity and accuracy of clinical trial data and is encouraged by regulators. A primary distinction in the types of ePRO platforms is between telephone-based interactive voice response systems and screen-based systems. Handheld touchscreen-based devices have become the mainstay for remote (i.e., off-site, unsupervised) PRO data collection in clinical trials. The conventional approach is to provide study subjects with a handheld device with a device-based proprietary software program. However, an emerging alternative for clinical trials is called bring your own device (BYOD). Leveraging study subjects' own Internet-enabled mobile devices for remote PRO data collection (via a downloadable app or a Web-based data collection portal) has become possible due to the widespread use of personal smartphones and tablets. However, there are a number of scientific and operational issues that must be addressed before BYOD can be routinely considered as a practical alternative to conventional ePRO data collection methods. Nevertheless, the future for ePRO data collection is bright and the promise of BYOD opens a new chapter in its evolution. PMID:25300613

  11. The neural chaperone proSAAS blocks α-synuclein fibrillation and neurotoxicity.

    PubMed

    Jarvela, Timothy S; Lam, Hoa A; Helwig, Michael; Lorenzen, Nikolai; Otzen, Daniel E; McLean, Pamela J; Maidment, Nigel T; Lindberg, Iris

    2016-08-01

    Emerging evidence strongly suggests that chaperone proteins are cytoprotective in neurodegenerative proteinopathies involving protein aggregation; for example, in the accumulation of aggregated α-synuclein into the Lewy bodies present in Parkinson's disease. Of the various chaperones known to be associated with neurodegenerative disease, the small secretory chaperone known as proSAAS (named after four residues in the amino terminal region) has many attractive properties. We show here that proSAAS, widely expressed in neurons throughout the brain, is associated with aggregated synuclein deposits in the substantia nigra of patients with Parkinson's disease. Recombinant proSAAS potently inhibits the fibrillation of α-synuclein in an in vitro assay; residues 158-180, containing a largely conserved element, are critical to this bioactivity. ProSAAS also exhibits a neuroprotective function; proSAAS-encoding lentivirus blocks α-synuclein-induced cytotoxicity in primary cultures of nigral dopaminergic neurons, and recombinant proSAAS blocks α-synuclein-induced cytotoxicity in SH-SY5Y cells. Four independent proteomics studies have previously identified proSAAS as a potential cerebrospinal fluid biomarker in various neurodegenerative diseases. Coupled with prior work showing that proSAAS blocks β-amyloid aggregation into fibrils, this study supports the idea that neuronal proSAAS plays an important role in proteostatic processes. ProSAAS thus represents a possible therapeutic target in neurodegenerative disease. PMID:27457957

  12. proBAMsuite, a Bioinformatics Framework for Genome-Based Representation and Analysis of Proteomics Data*

    PubMed Central

    Wang, Xiaojing; Slebos, Robbert J. C.; Chambers, Matthew C.; Tabb, David L.; Liebler, Daniel C.; Zhang, Bing

    2016-01-01

    To facilitate genome-based representation and analysis of proteomics data, we developed a new bioinformatics framework, proBAMsuite, in which a central component is the protein BAM (proBAM) file format for organizing peptide spectrum matches (PSMs)1 within the context of the genome. proBAMsuite also includes two R packages, proBAMr and proBAMtools, for generating and analyzing proBAM files, respectively. Applying proBAMsuite to three recently published proteomics datasets, we demonstrated its utility in facilitating efficient genome-based sharing, interpretation, and integration of proteomics data. First, the interpretation of proteomics data is significantly enhanced with the rich genomic annotation information. Second, PSMs can be easily reannotated using user-specified gene annotation schemes and assembled into both protein and gene identifications. Third, using the genome as a common reference, proBAMsuite facilitates seamless proteomics and proteogenomics data integration. Finally, proBAM files can be readily visualized in genome browsers and thus bring proteomics data analysis to a general audience beyond the proteomics community. Results from this study establish proBAMsuite as a useful bioinformatics framework for proteomics and proteogenomics research. PMID:26657539

  13. Experimental results from RO-PRO: a next generation system for low-energy desalination.

    PubMed

    Achilli, Andrea; Prante, Jeri L; Hancock, Nathan T; Maxwell, Eric B; Childress, Amy E

    2014-06-01

    A pilot system was designed and constructed to evaluate reverse osmosis (RO) energy reduction that can be achieved using pressure-retarded osmosis (PRO). The RO-PRO experimental system is the first known system to utilize energy from a volume of water transferred from atmospheric pressure to elevated pressure across a semipermeable membrane to prepressurize RO feedwater. In other words, the system demonstrated that pressure could be exchanged between PRO and RO subsystems. Additionally, the first experimental power density data for a RO-PRO system is now available. Average experimental power densities for the RO-PRO system ranged from 1.1 to 2.3 W/m2. This is higher than previous river-to-sea PRO pilot systems (1.5 W/m2) and closer to the goal of 5 W/m2 that would make PRO an economically feasible technology. Furthermore, isolated PRO system testing was performed to evaluate PRO element performance with higher cross-flow velocities and power densities exceeding 8 W/m2 were achieved with a 28 g/L NaCl draw solution. From this empirical data, inferences for future system performance can be drawn that indicate future RO-PRO systems may reduce the specific energy requirements for desalination by ∼1 kWh/m3. PMID:24798068

  14. Effective production of Pro-Gly by mutagenesis of l-amino acid ligase.

    PubMed

    Kino, Haruka; Nakajima, Shota; Arai, Toshinobu; Kino, Kuniki

    2016-08-01

    l-Amino acid ligase (Lal) catalyzes dipeptide synthesis from unprotected l-amino acids by hydrolysis ATP to ADP. Each Lal displays unique substrate specificity, and many different dipeptides can be synthesized by selecting suitable Lal. We have already successfully synthesized Met-Gly selectively by replacing the Pro85 residues of Lal from Bacillus licheniformis (BL00235). From these results, we deduced that the amino acid residue at position 85 had a key role in enzyme activity, and applied these findings to other Lals. When Pro and Gly were used as substrates, TabS from Pseudomonas syringae, synthesized the salt taste enhancing dipeptide Pro-Gly and other three dipeptides (Gly-Pro, Pro-Pro, and Gly-Gly) was hardly synthesized from its substrate specificity. However, the amount of Pro-Gly was low. Therefore, to alter the substrate specificity and increase the amount of Pro-Gly, we selected amino acid residues that might affect the enzyme activity, Ser85 corresponding to Pro85 of BL00235, and His294 on the results from previous studies and the predicted structure of TabS. These residues were replaced with 20 proteogenic amino acids, and Pro-Gly synthesizing reactions were conducted. The S85T and the H294D mutants synthesized more Pro-Gly than wild-type. Furthermore, the S85T/H294D double mutant synthesized considerably more Pro-Gly than the single mutant did. These results showed that the amino acid position 85 of TabS affect the enzyme activity similarly to BL00235. In addition, replacing the amino acid residue positioning around the N-terminal substrate and constructing the double mutant led to increase the amount of Pro-Gly. PMID:27017332

  15. Assessment of tennis elbow using the Marcy Wedge-Pro.

    PubMed Central

    Smith, R W; Mani, R; Cawley, M I; Englisch, W; Eckenberger, P

    1993-01-01

    The Marcy Wedge-Pro (MWP), a device used in training by tennis players, was employed in the assessment of tennis elbow. The MWP was used to measure the ability of patients to perform wrist extension exercises, since pain resulting from this specific activity is a prominent symptom of the condition. The MWP results were compared with clinical measures and found to identify accurately patients who responded to treatment (P < 0.05). This study illustrates the potential of the MWP to assess tennis elbow quantitatively. Images Figure 1 PMID:8130959

  16. The Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    Lorenzini, Enrico C.; Estes, Robert D.; Cosmo, Mario L.

    2001-01-01

    This is the Annual Report #2 entitled "The Propulsive Small Expendable Deployer System (ProSEDS)" prepared by the Smithsonian Astrophysical Observatory for NASA Marshall Space Flight Center. This report covers the period of activity from 1 August 2000 through 30 July 2001. The topics include: 1) Updated System Performance; 2) Mission Analysis; 3) Updated Dynamics Reference Mission; 4) Updated Deployment Control Profiles and Simulations; 5) Comparison of ED tethers and electrical thrusters; 6) Kalman filters for mission estimation; and 7) Delivery of interactive software for ED tethers.

  17. PRoViDE: Planetary Probes' Mass Vision Data Processing

    NASA Astrophysics Data System (ADS)

    Paar, G.; Muller, J.-P.; Tao, Y.; Barnes, D. P.; Gupta, S.

    2013-09-01

    The FP7-SPACE project PRoViDE will assemble a major portion of the imaging data gathered so far from vehicles and probes on planetary surfaces into a unique database, bringing them into a common planetary geospatial context and providing access to a complete set of 3D vision products. Processing and GIS web access is complemented by a multi-resolution visualisation engine that combines various levels of detail for a seamless and immersive real-time access to dynamically rendered 3D scene representations.

  18. Rotation Manager Pro Version 1.0b1

    Energy Science and Technology Software Center (ESTSC)

    2002-02-01

    The Rotation Manager Pro Package maintains databases of instructions to replicate plate tectonic movements. The instructions are in the standard of tectonic plate rotations, including plate identification and location and angle of the rotation pole. Each database is accompanied by various metadata, including information about each rotation pole and the database itself. The package provides a range of tools to actively manage the database using methods specifically required for rotations: rotation pole addition and subtraction,more » viewing of a rotation chain through the rotation hierarchy, and the rotation of data points.« less

  19. Rotation Manager Pro Version 1.0b1

    SciTech Connect

    Moore, Thomas L.; Scotese, Christopher

    2002-02-01

    The Rotation Manager Pro Package maintains databases of instructions to replicate plate tectonic movements. The instructions are in the standard of tectonic plate rotations, including plate identification and location and angle of the rotation pole. Each database is accompanied by various metadata, including information about each rotation pole and the database itself. The package provides a range of tools to actively manage the database using methods specifically required for rotations: rotation pole addition and subtraction, viewing of a rotation chain through the rotation hierarchy, and the rotation of data points.

  20. The Propulsive Small Expendable Deployer System (ProSEDS)

    NASA Technical Reports Server (NTRS)

    Lorenzini, Enrico C.

    2002-01-01

    This Annual Report covers the following main topics: 1) Updated Reference Mission. The reference ProSEDS (Propulsive Small Expendable Deployer System) mission is evaluated for an updated launch date in the Summer of 2002 and for the new 80-s current operating cycle. Simulations are run for nominal solar activity condition at the time of launch and for extreme conditions of dynamic forcing. Simulations include the dynamics of the system, the electrodynamics of the bare tether, the neutral atmosphere and the thermal response of the tether. 2) Evaluation of power delivered by the tether system. The power delivered by the tethered system during the battery charging mode is computed under the assumption of minimum solar activity for the new launch date. 3) Updated Deployment Control Profiles and Simulations. A number of new deployment profiles were derived based on the latest results of the deployment ground tests. The flight profile is then derived based on the friction characteristics obtained from the deployment tests of the F-1 tether. 4) Analysis/estimation of deployment flight data. A process was developed to estimate the deployment trajectory of the endmass with respect to the Delta and the final libration amplitude from the data of the deployer turn counters. This software was tested successfully during the ProSEDS mission simulation at MSFC (Marshall Space Flight Center) EDAC (Environments Data Analysis Center).

  1. Do Null Subjects (mis-)Trigger Pro-drop Grammars?

    PubMed

    Frazier, Lyn

    2015-12-01

    Native speakers of English regularly hear sentences without overt subjects. Nevertheless, they maintain a [−pro] grammar that requires sentences to have an overt subject. It is proposed that listeners of English recognize that speakers reduce predictable material and thus attribute null subjects to this process, rather than changing their grammars to a [−pro] setting. Mack et al. (J Memory Lang 67(1):211-223, 2012) showed that sentences with noise covering the subject are analyzed as having null subjects more often with a first person pronoun and with a present tense--properties correlated with more predictable referents--compared to a third person pronoun and past tense. However, those results might in principle have been due to reporting null subjects for verbs that often occur with null subjects. An experiment is reported here in which comparable results are found for sentences containing nonsense verbs. Participants preferred a null subject more often for first person present tense sentences than for third person past tense sentences. The results are as expected if participants are responding to predictability, the likelihood of reduction, rather than to lexical statistics. The results are argued to be important in removing a class of mis-triggering examples from the language acquisition problem. PMID:25086703

  2. Development of novel cyclic peptides as pro-apoptotic agents.

    PubMed

    Brindisi, Margherita; Maramai, Samuele; Brogi, Simone; Fanigliulo, Emanuela; Butini, Stefania; Guarino, Egeria; Casagni, Alice; Lamponi, Stefania; Bonechi, Claudia; Nathwani, Seema M; Finetti, Federica; Ragonese, Francesco; Arcidiacono, Paola; Campiglia, Pietro; Valenti, Salvatore; Novellino, Ettore; Spaccapelo, Roberta; Morbidelli, Lucia; Zisterer, Daniela M; Williams, Clive D; Donati, Alessandro; Baldari, Cosima; Campiani, Giuseppe; Ulivieri, Cristina; Gemma, Sandra

    2016-07-19

    Our recent finding that paclitaxel behaves as a peptidomimetic of the endogenous protein Nur77 inspired the design of two peptides (PEP1 and PEP2) reproducing the effects of paclitaxel on Bcl-2 and tubulin, proving the peptidomimetic nature of paclitaxel. Starting from these peptide-hits, we herein describe the synthesis and the biological investigation of linear and cyclic peptides structurally related to PEP2. While linear peptides (2a,b, 3a,b, 4, 6a-f) were found inactive in cell-based assays, biological analysis revealed a pro-apoptotic effect for most of the cyclic peptides (5a-g). Cellular permeability of 5a (and also of 2a,b) on HL60 cells was assessed through confocal microscopy analysis. Further cellular studies on a panel of leukemic cell lines (HL60, Jurkat, MEC, EBVB) and solid tumor cell lines (breast cancer MCF-7 cells, human melanoma A375 and 501Mel cells, and murine melanoma B16F1 cells) confirmed the pro-apoptotic effect of the cyclic peptides. Cell cycle analysis revealed that treatment with 5a, 5c, 5d or 5f resulted in an increase in the number of cells in the sub-G0/G1 peak. Direct interaction with tubulin (turbidimetric assay) and with microtubules (immunostaining experiments) was assessed in vitro for the most promising compounds. PMID:27150036

  3. idRHa+ProMod - Rail Hardening Control System

    NASA Astrophysics Data System (ADS)

    Ferro, L.

    2016-03-01

    idRHa+ProMod is the process control system developed by Primetals Technologies to foresee the thermo-mechanical evolution and micro-structural composition of rail steels subjected to slack quenching into idRHa+ Rail Hardening equipments in a simulation environment. This tool can be used both off-line or in-line, giving the user the chance to test and study the best cooling strategies or letting the automatic control system free to adjust the proper cooling recipe. Optimization criteria have been tailored in order to determine the best cooling conditions according to the metallurgical requirements imposed by the main rail standards and also taking into account the elastoplastic bending phenomena occurrin