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1

Clinical impact of occult HBV infections.  

PubMed

HBV infection in the absence of HBsAg has been a matter of debate for years, but its existence and clinical relevance are now supported by many publications, editorials and reviews. HBV DNA without HBs antigenemia was detected in the following clinical situations: (1) Chronic, presumably viral, hepatitis unrelated to HCV, atypical alcoholic hepatitis and hepatocellular carcinoma (HCC); (2) viral reactivation following immunosuppression; (3) Transmission through transplantation, transfusion or experimental transmission to chimpanzees. Occult HBV infections are not restricted to areas of high HBV endemicity. Indeed, such cases have been described in Western countries including France. It is now established that occult HBV infection among non-HCV patients suffering from chronic hepatitis varies from 20% to 30% in Europe, and in the context of HCV infection it varies from 20% in France up to 80% in Japan. The percentage of occult HBV infections among non A-E cases depends on several parameters: (1) The method of detection, including PCR primer selection; (2) patient recruitment; (3) patients from countries highly endemic for HBV are more likely to develop occult HBV infections; (4) prevalence may also vary depending on the nature of biological material tested, with a higher proportion for liver compared to serum specimen. The mechanisms leading to HCC in occult HBV infection seem similar to those overt cases, patients with low-grade but diagnosable HBV replication that retains its pro-oncogenic properties. During the course of HCV infection, occult HBV infection may worsen liver damage induced by HCV and reduce the response to HCV antiviral treatment. Occult HBV infection is a frequent phenomenon and HBV DNA testing with highly sensitive PCR in the clinical setting is therefore becoming of paramount importance. PMID:16461218

Chemin, I; Trépo, C

2005-12-01

2

Indirect hyperbilirubinemia in HBV carriers  

Microsoft Academic Search

Summary  Indirect hyperbilirubinemia without any other abnormalities of liver function tests was seen in 14.3% inHBV carriers and 1.2% in controls in the previous study. In order to clarify the mechanism of hyperbili-rubinemia inHBV carriers, 33HBV carriers with normal liver functions regardless of hyperbilirubinemia and with no past history of acute hepatitis were investigated\\u000a clinically. Most ofHBV carriers with indirect hyperbilirubinemia

Kensuke Miura; Shiro Suzuki; Satoshi Tanaka; Ryota Kinoshita; Haruto Uchino; Shinichi Hirose; Tadayuki Nakagawa; Yukio Imai

1980-01-01

3

High pretransplant HBV level predicts HBV reactivation after kidney transplantation in HBV infected recipients  

PubMed Central

Purpose HBsAg-positive kidney recipients are at increased risk for mortality and graft failure. The aims of this study were to identify the outcomes of HBsAg-positive recipients who received preemptive antiviral agents after successful kidney transplantation and to analyze risk factors for HBV reactivation. Methods We retrospectively reviewed the medical records of 944 patients performed kidney transplantation between 1999 and 2010. Results HBsAg-negative recipients were 902 patients and HBsAg-positive recipients, 42. Among HBsAg-positive recipients, HBV reactivation was detected in 7 patients and well controlled by switch or combination therapy. Graft failure developed in only one patient due to chronic rejection regardless of HBV reactivation but no deaths occurred. All patients were alive at the end of follow-up and none developed end-stage liver disease or hepatocellular carcinoma. There was statistically significant difference in graft survival between HBsAg-positive recipients and HBsAg-negative. Multivariate analysis identified increased HBV DNA levels (>5 × 104 IU/mL) in the HBsAg-positive kidney transplant recipients as a risk factor for HBV reactivation (P = 0.007). Conclusion Effective viral suppression with antiviral agents in HBsAg-positive renal transplant recipients improves patient outcome and allograft survival. Antiviral therapy may be especially beneficial in patients with high HBV DNA levels prior to transplantation.

Kim, Jong Man; Park, Hyojun; Jang, Hye Ryoun; Park, Jae Berm; Kwon, Choon Hyuck David; Huh, Wooseong; Lee, Joon Hyeok; Joh, Jae-Won

2014-01-01

4

Impact of HBV therapy on the incidence of hepatocellular carcinoma.  

PubMed

Hepatocellular carcinoma (HCC) is a frequent, long term complication of chronic infection with hepatitis B virus (HBV) with an annual incidence ranging from 2 to 5%, often independent from the histological stage of underlying liver disease and serological status. Nevertheless, HCC is more often seen in older patients in whom HBV has been asserting its pro-oncogenic properties through both indirect and direct mechanisms. In Europe, HBV-related HCC is associated with cirrhosis in most patients, whereas this is not true in Asia and Africa where the tumour is also common among carriers with mild hepatic fibrosis, probably because of the coexistence of environmental co-carcinogens (aflatoxin) and long standing infection that is often acquired perinatally. Since hepatitis B-related carcinogenesis develops independently of the onset of cirrhosis, antiviral treatments such as nucleo(t)side analogues (NAs) that may result in the regression of fibrosis, prevent clinical decompensation and variceal bleeding, often fail to prevent HCC. Studies enrolling patients treated with lamivudine or rescued with adefovir, i.e. regimens characterized by limited potency and a low to moderate genetic barrier, have clearly been shown to help prevent HCC in patients with chronic hepatitis but not in those with cirrhosis, and in general not in patients that cannot achieve a sustained virological response. More potent anti-HBV drugs, such as entecavir and tenofovir, have been shown to improve the prevention of HCC in responders with cirrhosis, although HCC may still occur even in low risk patients. To attenuate HCC related outcomes, HBV replication must permanently be suppressed and HCC surveillance by abdominal ultrasound should be maintained even in responder patients. PMID:24373091

Triolo, Michela; Corte, Cristina Della; Colombo, Massimo

2014-02-01

5

HBV mutations in untreated HIV-HBV co-infection using genomic length sequencing  

PubMed Central

HIV infection has a significant impact on the natural progression of hepatitis B virus (HBV) related liver disease. In HIV-HBV co-infected patients, little is known about mutations in the HBV genome, which can influence severity of liver disease. The aim of this study was to characterize and to determine the frequency of known clinically-significant mutations in the HBV genomes from HIV-HBV co-infected patients and from HBV mono-infected patients. To accomplish this, genomic length HBV sequencing was performed in highly-active anti-retroviral therapy (HAART) –naïve HIV-HBV co-infected patients (n= 74) and in anti-HBV therapy-naïve HBV mono-infected patients (n=55). The frequency of HBV mutations differed between the co-infected and mono-infected patients when comparing patients with the same genotype. BCP mutations A1762T and G1764A were significantly more frequent in HBV genotype C mono-infection and the ?1G frameshift was significantly more frequent in co- infection and was only observed in HBV genotype A co-infection. PreS2 deletions were observed more frequently in the setting of co-infection. Further work is needed to determine if these mutational patterns influence the differences in liver disease progression in HIV-HBV co-infected and HBV mono-infected patients.

Audsley, Jennifer; Littlejohn, Margaret; Yuen, Lilly; Sasadeusz, Joe; Ayres, Anna; Desmond, Christopher; Spelman, Tim; Lau, George; Matthews, Gail V.; Avihingsanon, Anchalee; Seaberg, Eric; Philp, Frances; Saulynas, Melissa; Ruxrungtham, Kiat; Dore, Gregory J.; Locarnini, Stephen A.; Thio, Chloe L.; Lewin, Sharon R.; Revill, Peter A.

2010-01-01

6

Quantification of intrahepatic hepatitis B virus (HBV) DNA in patients with chronic HBV infection.  

PubMed

No data are available about the amount of hepatitis B virus (HBV) genomes in liver of patients with chronic HBV infection. The aim of this study was to quantify the intrahepatic HBV DNA in hepatitis B surface antigen (HBsAg)-positive patients with either active or suppressed viral replication and in HBsAg-negative subjects with occult HBV infection. We optimized the Roche "Amplicor HBV Monitor" kit for quantifying liver HBV DNA and analyzed hepatic DNA extracts and serum samples from 19 HBs-Ag-positive and 43 HBsAg-negative individuals. Eight of the HBsAg carriers had active HBV replication, and for 3 of them we analyzed samples obtained before and at the end of 1 year of lamivudine treatment. Five hepatitis Delta virus (HDV) coinfected patients and 6 healthy HBsAg carriers had inhibited HBV activity. Among the HBsAg-negative subjects 21 had occult HBV infection and 22 had no evidence of HBV infection. The median of HBV genomes per microgram of liver DNA milliliter of serum was 34,500 to 2,620,000 in patients with active viral replication, 20,000 to 3,900, 000 before and 10,000 to 2,800 at the end of therapy in lamivudine-treated individuals, 9,800 to 600 in HDV-infected individuals, and 7,450 to 17,400 in healthy HBsAg carriers. These data indicate that cases with suppressed HBV activity, despite the very low levels of viremia, maintain a relatively high amount of intrahepatic viral genomes. This virus reservoir is likely involved in HBV reactivation, which is usually observed after stopping lamivudine treatment. Finally, the analysis of cases with occult HBV infection showed that the assay we used was able to specifically detect and quantify as few as 100 copies of viral genomes per microgram of liver DNA. PMID:10655278

Cacciola, I; Pollicino, T; Squadrito, G; Cerenzia, G; Villari, D; de Franchis, R; Santantonio, T; Brancatelli, S; Colucci, G; Raimondo, G

2000-02-01

7

Post-transplant hepatitis: HCV and HBV  

Microsoft Academic Search

Chronic hepatitis C virus (HCV) is currently the leading indication for liver transplantation (LTx). Hepatitis B virus (HBV)\\u000a infection occurs less frequently and is associated with better treatment options in the perioperative period. The impact of\\u000a HCV and HBV in LTx is well recognized. However, therapeutic interventions are less standardized and often depend upon institutional\\u000a protocol. This article provides a

Guy W. Neff; Kenneth E. Sherman

2004-01-01

8

Current Management of HBV Antiviral Drug Resistance  

Microsoft Academic Search

Long-term administration of oral anti-hepatitis B virus (HBV) nucleoside or nucleotide analogues therapy (NUC) is the first-line\\u000a treatment option for most patients with chronic hepatitis B infection. Although NUC rapidly inhibits HBV replication in most\\u000a patients, in the long term, this therapeutic regimen is challenged by the emergence of drug-resistant mutant virions, ultimately\\u000a leading to treatment failure and liver disease

Pietro Lampertico; Mauro Viganò; Massimo Colombo

2011-01-01

9

Prospective comparison of Abbott RealTime HBV DNA and Versant HBV DNA 3.0 assays for hepatitis B DNA quantitation: impact on HBV genotype monitoring.  

PubMed

The quantitation of human hepatitis B virus (HBV) in the serum of infected patients is recommended to characterize the course of chronic HBV infection. The aim of this prospective study was to evaluate the performance of the Abbott RealTime PCR assay for HBV DNA quantitation by comparison with the standard Versant HBV DNA 3.0 assay. The better sensitivity and broader dynamic range of HBV DNA quantitation using the Abbott RealTime PCR assay was confirmed by the study of 362 serum samples from 311 patients. In addition, data analysis revealed the concordance of HBV DNA quantitations between the two assays. When this evaluation was assessed as a function of HBV genotype, there was discordance for HBV genotype C samples. Thus, we performed an in-house PCR to confirm the discrepancy observed regarding the HBV genotypes. The in-house PCR results agreed better with the Abbott RealTime PCR method when compared with the standard hybridization assay. In conclusion, the wide dynamic range of HBV DNA quantitation achieved with the Abbott RealTime PCR assay makes it appropriate for the clinical monitoring of HBV infected patients. However, a change of HBV DNA quantitation method could influence results on the follow-up of HBV genotype C infected patients. PMID:18929599

Pol, Jonathan; Le Pendeven, Catherine; Beby-Defaux, Agnes; Rabut, Elodie; Jais, Jean Philippe; Pilloux, Marilyse; Osada, Catherine; Zatla, Fadila; Assami, Hichem; Grange, Jean Didier; Kremsdorf, Dina; Nicolas, Jean Claude; Soussan, Patrick

2008-12-01

10

Occult HBV infection among Egyptian hepatocellular carcinoma patients  

PubMed Central

Background Occult HBV infection accelerates the progression of liver fibrosis, cirrhosis, and finally leading to hepatocellular carcinoma (HCC). This study analyzed the occult HBV-genotypes in HCC patients. Methods To achieve our objective, matched serum and tissue samples were collected from 40 HCC patients. Three sets of primers were used for the HBV-DNA detection by nested-PCR, which cover the HBV-genome; Core, Surface and X genes. Genotyping system based on PCR using type-specific primers was applied on HBV-DNA positive samples. Results Intrahepatic occult HBV-DNA was detected in 62.5%, whereas; Serum occult HBV-DNA were detected in only 22.5% of HCC patients. In patients' positive for both anti-HBs and anti-HBc, 10% had occult HBV in serum. In serologically negative HCV patients, 63% had intrahepatic HBV-DNA, and 21% had HBV-DNA in serum samples. HBV-genotype D (32%) and B (24%) attributed predominantly to intrahepatic HBV infections in HCC patients, whereas HBV-genotype A (4%) and C (8%) infections were the least observed. Conclusion This is the first study to show the genotypes of occult HBV infection in HCC Patients. We suggest that B or D may influence the outcome of HBV infection which may lead to the development of HCC.

2011-01-01

11

HBV vaccination in liver transplant recipients: not an effective strategy in the prophylaxis of HBV recurrence.  

PubMed

Anti-HBs immunoglobulins (HBIG) and lamivudine are main options to prevent hepatitis B virus (HBV) reinfection after liver transplantation. Although they are very effective, development of mutant viruses and high cost of treatment are main limitations for their application. Additionally there is an uncertainity for the duration of that prophylaxis regimen and its mostly applied indefinitely. Recently, post-transplant HBV vaccination is reported to be a cheaper alternative prophylaksis strategy, that enables discontinuation of HBIG. To investigate the efficacy of HBV vaccination in patients transplanted for HBV cirrhosis, we administered double course of double dose recombinant HBV vaccine (Genhavac B; containing HBV pre-S1, pre-S2, and S gene products). Vaccination has been started 1 month after HBIg discontinuation, and lamivudine (100 mg/day) was given throughout the study. The first cycle consisted of 0, 1- and 6-month schedule, and, in nonresponders, second cycle 0, 1-, 2-month schedule. Fourteen patients included into the study. Only one patient seroconverted (an anti-HBs titre of 37 IU/L) after the first cycle. No other patient responded to second cycle. HBV vaccination in the post-transplantation setting does not seems like an effective strategy in the prophylaxis of HBV recurrence. PMID:15720538

Karasu, Z; Ozacar, T; Akarca, U; Ersoz, G; Erensoy, S; Gunsar, F; Kobat, A; Tokat, Y; Batur, Y

2005-03-01

12

A mouse model for HBV immunotolerance and immunotherapy  

PubMed Central

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.

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

2014-01-01

13

Monocytes from Chronic HBV Patients React In Vitro to HBsAg and TLR by Producing Cytokines Irrespective of Stage of Disease  

PubMed Central

Individuals who are chronically infected with the hepatitis B virus (HBV) are highly heterogenous with respect to serum levels of HBV DNA, HBV particles and viral proteins. Since circulating leukocytes, such as monocytes, are constantly exposed to these viral components, it is likely that the functionality of these cells is affected. However, at present, little information is available on the consequences of the interaction between monocytes and viral components. Therefore, we examined the in vitro effects of HBV surface antigen (HBsAg) on monocytes and evaluated whether these effects were reflected in vivo. We observed that in vitro HBsAg exposure of monocytes induced robust production of IL-6 and TNF. However, between chronic HBV patients with distinct levels of serum HBsAg, HBV early antigen (HBeAg), and HBV DNA, TLR-induced monocyte cytokine production did not differ. Importantly, HBsAg-induced cytokine production by monocytes was similar between patients and healthy controls showing that earlier in vivo exposure to HBsAg does not affect the in vitro response. Additionally, we show that IL-10 is able to inhibit cytokine production by HBsAg-induced monocytes. In conclusion, we demonstrate that monocytes can recognize and respond to HBsAg, resulting in vigorous pro-inflammatory cytokine production in vitro. However, phenotype and function of the monocyte compartment in chronic HBV patients are not influenced by differences in levels of serum viral components, suggesting that regulatory mechanisms are active to avoid excessive in vivo monocyte activation.

Boltjes, Arjan; Groothuismink, Zwier M.; van Oord, Gertine W.; Janssen, Harry L. A.; Woltman, Andrea M.; Boonstra, Andre

2014-01-01

14

Virology and clinical sequelae of drug-resistant HBV in HIV-HBV co-infected patients on HAART  

PubMed Central

Summary Several of the nucleos(t)ide analogues used to treat HIV also inhibit hepatitis B virus (HBV) replication, with lamivudine being the oldest of this group. Thus, prior to licensing of tenofovir, many HIV-HBV co-infected subjects received lamivudine as the only active drug against HBV as part of the anti-HIV regimen setting the stage for emergence of drug-resistant HBV. In co-infected persons, lamivudine-resistant HBV develops more rapidly than in HBV moninfected persons, but it is not known if this is true for the newer agents. Due to overlapping reading frames of the HBV Polymerase and Surface antigens, drug-resistant changes in HBV Pol can lead to mutations in the envelope. This review will discuss studies of drug-resistant HBV in HIV-infected persons including drug-resistant mutations that have been identified and clinical sequelae of these mutations.

Thio, Chloe L.

2009-01-01

15

GP73, a new marker for diagnosing HBV-ACLF in population with chronic HBV infections.  

PubMed

Although Golgi protein 73 (GP73) has been widely evaluated for diagnosing hepatocellular carcinoma (HCC) and other liver diseases in recent decade, its serum profile of patients with hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) is still unknown. This study was designed to evaluate the serum levels of GP73 in patients with HBV-ACLF. The participants included 200 apparently healthy controls; 200 patients with chronic hepatitis B (CHB); 200 patients with HCC; 210 patients with HBV-ACLF, in which 29 HBV-ACLF patients were followed up for 3 months. All patients were Hepatitis B virus surface antigen (HBsAg) positive. The concentrations of GP73 in patients with HBV-ACLF (285.3 ± 128.5 ng/mL) were markedly higher than those HCC patients (159.1 ± 105.8 ng/mL), CHB patients (64.65 ± 44.99 ng/mL), and healthy controls (35.37 ± 12.41 ng/mL). When the cut-off value was set at 182.1 ng/mL, the sensitivity and specificity of HBV-ACLF diagnosis were 77.62% (95% confidence interval [CI]: 71.37%-83.07%) and 95.50% (95% CI: 92.27%-98.26%), respectively. If serum GP73 concentration was still above 361.6 ng/mL after 14 days of follow-up, the patient's prognosis may be depressed. Serum GP73 may be used to diagnosis HBV-ACLF in population with chronic HBV infections. PMID:24560809

Wei, Hongshan; Zhang, Jing; Li, Hongmin; Ren, Hui; Hao, Xiaohua; Huang, Yubo

2014-05-01

16

[Present state and the future direction of HBV vaccine].  

PubMed

Hepatitis B virus (HBV) prevention program in Japan is considered one of the most successful and effective public anti-counter programs to HBV infection. However, almost all of population under twenty-five years is extremely susceptibility for HBV infection. HBV genotype A, which was not in Japan and has been from western countries, is increasing in chronic hepatitis B patients in Japan as a consequence of acute hepatitis B spreading in the younger generation through promiscuous sexual transmitted infection and the characteristics of HBV genotype A is a prolonged high HBVDNA viremia compared with other HBV genotypes. These data have strongly indicated that the main transmission route of HBV in Japan has been changed to a horizontal infection with sexual transmitted disease from perinatal transmission from HBsAg positive mothers. Although the HBV vaccine has tipped the balance in our favor, newly issues of HBV vaccine has been arisen such as vaccine escape mutant, efficacy and potency for the prevention of HBV infection, especially different HBV genotypes, HBV reactivation on the patients with HBsAg negative and anti-HBs antibody positive under systemic chemotherapy, and universal vaccination or selective vaccination and so on. PMID:23189826

Mizokami, Masashi; Sugiyama, Masaya

2012-06-01

17

Neutralization of hepatitis B virus (HBV) by human monoclonal antibody against HBV surface antigen (HBsAg) in chimpanzees  

Microsoft Academic Search

The virus neutralizing efficacy of HB-C7A, a human monoclonal antibody raised against the surface antigen of hepatitis B virus (HBsAg), was proved using hepatitis B virus (HBV)-naïve chimpanzees. One control chimpanzee which received 100CID50 of HBV, subtype adw, without HB-C7A antibody became infected by HBV as evidenced by the appearance of HBV DNA on week 10 and subsequent appearance of

Se-Ho Kim; Yong Won Shin; Kwang-Won Hong; Ki-Hwan Chang; Kyung-Hwan Ryoo; Sang-Hoon Paik; Jin-Man Kim; Betsy Brotman; Wolfram Pfahler; Alfred M. Prince

2008-01-01

18

HBV life cycle and novel drug targets  

Microsoft Academic Search

With up to 400 million affected people worldwide, chronic hepatitis B virus (HBV) infection is still a major health care problem.\\u000a During the last decade, several novel therapeutic approaches have been developed and evaluated. In most regions of the world,\\u000a interferon-?, and nucleos(t)ide analogues (NUCs) are currently approved. Despite major improvements, none of the existing\\u000a therapies is optimal since viral

Daniel Grimm; Robert Thimme; Hubert E. Blum

2011-01-01

19

Managing HBV in patients with impaired immunity  

Microsoft Academic Search

Chronic hepatitis B is one of the most common infectious diseases worldwide. In patients with an impaired immune system the prevalence of HBsAg is even higher and the course of hepatitis B infection is often aggravated. In HIV\\/HBV co-infected patients, liver related morbidity and mortality can be reduced by implementing highly active antiretroviral treatment (HAART) that contains substances active against

Karsten Wursthorn; Heiner Wedemeyer; Michael P Manns

2010-01-01

20

Reduced Hepatitis B Virus (HBV)Specific CD4+ T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy  

Microsoft Academic Search

Functional hepatitis B virus (HBV)-specific T cells are significantly diminished in individuals chronically infected with HBV compared to individuals with self-limiting HBV infection or those on anti-HBV therapy. In individuals infected with human immunodeficiency virus type 1 (HIV-1), coinfection with HBV is associated with an increased risk of worsening liver function following antiviral therapy and of more rapid HBV disease

J. Judy Chang; Fiona Wightman; Angeline Bartholomeusz; Anna Ayres; Stephen J. Kent; Joseph Sasadeusz; Sharon R. Lewin

2005-01-01

21

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

PubMed Central

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.

Roman, Sonia; Panduro, Arturo

2013-01-01

22

Future directions in the treatment of HIV-HBV coinfection  

PubMed Central

Liver disease is a major cause of mortality in individuals with HIV–HBV coinfection. The pathogenesis of liver disease in this setting is unknown, but is likely to involve drug toxicity, infection of hepatic cells with both HIV and HBV, and an altered immune response to HBV. The availability of therapeutic agents that target both HIV and HBV replication enable dual viral suppression, and assessment of chronic hepatitis B is important prior to commencement of antiretroviral therapy. Greater importance is now placed on HBV DNA levels and staging of liver fibrosis, either by liver biopsy or noninvasive measurement, such as transient elastography, since significant liver fibrosis may exist in the presence of normal liver function tests. Earlier treatment of both HIV and HBV is now generally advocated and treatment is usually lifelong.

Iser, David M; Lewin, Sharon R

2009-01-01

23

Innate immune responses in hepatitis B virus (HBV) infection  

PubMed Central

Hepatitis B virus (HBV) infection has a low rate of chronicity compared to HCV infection, but chronic liver inflammation can evolve to life threatening complications. Experimental data from HBV infected chimpanzees and HBV transgenic mice have indicated that cytotoxic T cells are the main cell type responsible for inhibition of viral replication, but also for hepatocyte lysis during chronic HBV infection. Their lower activation and impaired function in later stages of infection was suggested as a possible mechanism that allowed for low levels of viral replication. The lack of an interferon response in these models also indicated the importance of adaptive immunity in clearing the infection. Increased knowledge of the signalling pathways and pathogen associated molecular patterns that govern activation of innate immunity in the early stages of viral infections in general has led to a re-evaluation of the innate immune system in HBV infection. Numerous studies have shown that HBV employs active strategies to evade innate immune responses and induce immunosuppression. Some of the immune components targeted by HBV include dendritic cells, natural killer cells, T regulatory cells and signalling pathways of the interferon response. This review will present the current understanding of innate immunity in HBV infection and of the challenges associated with clearing of the HBV infection.

2014-01-01

24

Neutralization of hepatitis B virus (HBV) by human monoclonal antibody against HBV surface antigen (HBsAg) in chimpanzees.  

PubMed

The virus neutralizing efficacy of HB-C7A, a human monoclonal antibody raised against the surface antigen of hepatitis B virus (HBsAg), was proved using hepatitis B virus (HBV)-naïve chimpanzees. One control chimpanzee which received 100CID(50) of HBV, subtype adw, without HB-C7A antibody became infected by HBV as evidenced by the appearance of HBV DNA on week 10 and subsequent appearance of HBsAg, anti-HBc and anti-HBs in the serum. Two experimental chimpanzees were inoculated intravenously with same dose of HBV as the control chimpanzee, which was previously incubated with 0.1mg and 10mg of HB-C7A antibody prior to inoculation. HBV infection was not observed in the antibody-treated chimpanzees during 12 months of follow-up, exhibiting neither detectable HBsAg nor anti-HBc antibody. This work demonstrates the neutralization of HBV by HB-C7A monoclonal antibody and shows the possibility of prevention of HBV infection using this antibody in liver transplantation and exposure to HBV. PMID:18479762

Kim, Se-Ho; Shin, Yong Won; Hong, Kwang-Won; Chang, Ki-Hwan; Ryoo, Kyung-Hwan; Paik, Sang-Hoon; Kim, Jin-Man; Brotman, Betsy; Pfahler, Wolfram; Prince, Alfred M

2008-09-01

25

Bloodborne Pathogens: HIV and HBV Contagion Risks at Camp.  

ERIC Educational Resources Information Center

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…

Skaros, Susan

1996-01-01

26

Advances in Molecular Diagnosis of HBV Infection and Drug Resistance  

PubMed Central

Serological markers are key elements in diagnosing acute hepatitis B virus (HBV) infection and determining its possible evolution towards chronicity. Once treatment of chronic HBV is initiated with approved anti-hepadnaviral agents, such as lamivudine, interferon-alpha, or adefovir dipivoxil, the measurement of HBV DNA in serum can not only help monitor treatment efficacy but also indicates breakthrough infection should drug resistance emerge. Advances in the molecular diagnosis of drug resistance using highly sensitive methodologies such as DNA hybridization assays can further pinpoint the type of mutation responsible and, more importantly, detect upcoming viral resistance at an early stage when the variant represents only a minor fraction of the total viral population. Such new tools are especially relevant for patients at high risk for disease progression or acute exacerbation. Recent diagnostic developments including HBV genotyping and precore/core promoter assays that could well play important future roles in HBV patient management are also reviewed.

2005-01-01

27

Hepatitis B virus (HBV) infection and recombination between HBV genotypes D and E in asymptomatic blood donors from Khartoum, Sudan.  

PubMed

Sudan is a highly endemic area for hepatitis B virus (HBV), and >5% of blood donors are chronically infected. To examine potential strategies to improve HBV blood safety, 404 replacement donor samples previously screened for HBV surface antigen (HBsAg) were tested for antibody to HBV core (anti-HBc), anti-surface antigen (anti-HBs), and HBV DNA. Of 145 anti-HBc-containing samples (36%) identified, 16 retested were HBsAg positive (11%). Anti-HBs was detected in 43/77 (56%) anti-HBc-reactive samples. Six samples were HBsAg(-)/anti-HBc(+)/anti-HBs(+) and contained HBV DNA, meeting the definition of occult HBV infection (OBI). OBIs had low HBV DNA loads (<10 IU/ml) and were genotype B (n = 1) or genotype D (n = 5). Pre-S/S and/or whole genome sequences were obtained from 47 randomly selected HBsAg-positive donors added to the previous 16. Genotype E was identified in 27 strains (57.5%), genotype D in 19 strains (40.5%), and genotype A2 in 1 strain (2%). Two outlier strains within genotype D ultimately were identified as recombinants of genotypes D and E with identical recombination points, suggesting circulating, infectious, recombinant strains. Anti-HBc screening does not appear to be a sustainable blood safety strategy because of the cost and the negative impact on the Sudanese blood supply, even when reduced by anti-HBs testing. Being at the junction between two main African HBV genotypes, genetic recombination occurred and became part of the molecular epidemiology of HBV in Sudan. PMID:21048009

Mahgoub, Shaza; Candotti, Daniel; El Ekiaby, Magdy; Allain, Jean-Pierre

2011-01-01

28

Hepatitis B Virus (HBV) Infection and Recombination between HBV Genotypes D and E in Asymptomatic Blood Donors from Khartoum, Sudan ?  

PubMed Central

Sudan is a highly endemic area for hepatitis B virus (HBV), and >5% of blood donors are chronically infected. To examine potential strategies to improve HBV blood safety, 404 replacement donor samples previously screened for HBV surface antigen (HBsAg) were tested for antibody to HBV core (anti-HBc), anti-surface antigen (anti-HBs), and HBV DNA. Of 145 anti-HBc-containing samples (36%) identified, 16 retested were HBsAg positive (11%). Anti-HBs was detected in 43/77 (56%) anti-HBc-reactive samples. Six samples were HBsAg?/anti-HBc+/anti-HBs+ and contained HBV DNA, meeting the definition of occult HBV infection (OBI). OBIs had low HBV DNA loads (<10 IU/ml) and were genotype B (n = 1) or genotype D (n = 5). Pre-S/S and/or whole genome sequences were obtained from 47 randomly selected HBsAg-positive donors added to the previous 16. Genotype E was identified in 27 strains (57.5%), genotype D in 19 strains (40.5%), and genotype A2 in 1 strain (2%). Two outlier strains within genotype D ultimately were identified as recombinants of genotypes D and E with identical recombination points, suggesting circulating, infectious, recombinant strains. Anti-HBc screening does not appear to be a sustainable blood safety strategy because of the cost and the negative impact on the Sudanese blood supply, even when reduced by anti-HBs testing. Being at the junction between two main African HBV genotypes, genetic recombination occurred and became part of the molecular epidemiology of HBV in Sudan.

Mahgoub, Shaza; Candotti, Daniel; El Ekiaby, Magdy; Allain, Jean-Pierre

2011-01-01

29

Lack of implementation of Hepatitis B Virus (HBV) vaccination policy in household contacts of HBV carriers in Italy  

PubMed Central

Background In Italy, HBV vaccination is recommended and offered free of charge through the National Health Service to selected population groups – e.g., family members of an HBsAg carrier, healthcare workers, newborns and those who were 12-years old in 1991. However, a significant proportion of cases of acute hepatitis B still occur in Italy among persons who should have been vaccinated. We analysed HBV sero-prevalence data of two vaccination target populations (people born after 1980 and household contacts of an HBV carrier) living in a southern Italian area in order to evaluate HBV vaccine coverage and its possible determinants. Methods Between 2003 and 2006, we carried out a cross-sectional, population-based, sero-epidemiological survey on HBV infection on 4496 randomly selected individuals (aged 20 years or more) from the general population of the province of Naples. Sera were tested for antibodies to hepatitis B core antigen (anti-HBc) and to hepatitis B surface antigen (anti-HBsAg) by commercial immunoassays. Prevalence of past or current HBV infection and of HBV vaccination-induced immunity was calculated in two vaccination target populations. To analyze the association of epidemiological and socioeconomic characteristics with HBV vaccination of household contacts, we calculated crude and multiple logistic regression (MLR) odds ratio (OR). Results Prevalence of HBV vaccine-induced immunity (anti-HBs alone) was much lower among household contacts (25%) than among those who had been targeted for universal adolescent vaccination (81.6%). Male sex, older age, unemployment and lower education levels were associated to lower immunization rates. Conclusion Understanding the different uptake of hepatitis B vaccination in these populations may provide useful information for optimizing vaccination campaigns in other contexts. Our data clearly demonstrated the need of improving the uptake of vaccination for household contacts of HBV carriers.

2009-01-01

30

Analysis of residual perinatal transmission of hepatitis B virus (HBV) and of genetic variants in human immunodeficiency virus and HBV co-infected women and their offspring  

PubMed Central

Background Despite implementation of universal infant hepatitis B (HB) vaccination, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) still occurs. Limited data are available on the residual MTCT of HBV in human immunodeficiency virus (HIV)-HBV co-infected women. Objectives We assessed the prevalence of HBV infection among HIV-infected pregnant women and the rate of residual MTCT of HBV from HIV-HBV co-infected women and analyzed the viral determinants in mothers and their HBV-infected children. Study design HIV-1 infected pregnant women enrolled in two nationwide perinatal HIV prevention trials in Thailand were screened for HB surface antigen (HBsAg) and tested for HBeAg and HBV DNA load. Infants born to HBsAg-positive women had HBsAg and HBV DNA tested at 4–6 months. HBV diversity within each HBV-infected mother-infant pair was analyzed by direct sequencing of amplified HBsAg-encoding gene and cloning of amplified products. Results Among 3,312 HIV-1 infected pregnant women, 245 (7.4%) were HBsAg-positive, of whom 125 were HBeAg-positive. Of 230 evaluable infants born to HBsAg-positive women, 11 (4.8%) were found HBsAg and HBV DNA positive at 4–6 months; 8 were born to HBeAg-positive mothers. HBV genetic analysis was performed in 9 mother-infant pairs and showed that 5 infants were infected with maternal HBV variants harboring mutations within the HBsAg “a” determinant, and four were infected with wild-type HBV present in highly viremic mothers. Conclusions HBV-MTCT still occurs when women have high HBV DNA load and/or are infected with HBV variants. Additional interventions targeting highly viremic women are thus needed to reduce further HBV-MTCT.

Khamduang, Woottichai; Gaudy-Graffin, Catherine; Ngo-Giang-Huong, Nicole; Jourdain, Gonzague; Moreau, Alain; Borkird, Thitiporn; Layangool, Prapaisri; Kamonpakorn, Nareerat; Jitphiankha, Weerachai; Kwanchaipanich, Ratchanee; Potchalongsin, Sathit; Lallemant, Marc; Sirirungsi, Wasna; Goudeau, Alain

2013-01-01

31

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

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.

2011-01-01

32

Current treatment of chronic HBV infection: A North American perspective  

Microsoft Academic Search

Chronic hepatitis B virus (HBV) infection remains a major cause of liver disease and hepatocellular carcinoma worldwide. Although\\u000a less prevalent in the United States than in other areas of the world, HBV infection results in a significant disease burden\\u000a in many American immigrant communities. Seven treatments are approved by the US Food and Drug Administration for the treatment\\u000a of chronic

Hui-Hui Tan; Paul Martin

2009-01-01

33

What technique should be used for routine detection and quantification of HBV DNA in clinical samples?  

Microsoft Academic Search

Detection of hepatitis B virus (HBV) DNA in serum allows monitoring of HBV replication and assessing responses to antiviral treatment. HBV DNA quantification measures virus replication and can be used as a prognosis indicator of liver disease and an index of response to antiviral drugs. The aim of this study was to compare the performances of three HBV DNA detection

Jean-Michel Pawlotsky; Anne Bastie; Isabelle Lonjon; Jocelyne Re´mire´; Françoise Darthuy; Claude-James Soussy; Daniel Dhumeaux

1997-01-01

34

Primary and secondary prevention of liver cancer caused by HBV  

PubMed Central

Primary cancer of the liver (hepatocellular carcinoma, HCC) is one of the most common cancers worldwide; HBV is the major cause of HCC. A vaccine that protects against HBV infection was invented in 1969 and is now one of the most commonly used vaccines. National vaccination programs have dramatically reduced the prevalence of HBV infection and carriers, with a concomitant decrease in the incidence of HCC in the vaccine-impacted populations. HBV vaccine is the first widely used cancer prevention vaccine; a second that protects against papilloma virus and cancer of the cervix has recently been introduced. Appropriate treatment of HBV carriers with antivirals can reduce the titers of HBV in their blood and thereby greatly reduce the risk of HCC and chronic liver disease. Further data are required to establish criterion for treatment to enable protocols for medical and prevention programs. There are other viral caused cancers and an understanding of their pathogenesis is an important future direction for research to reduce the human burden of cancer.

Blumberg, Baruch S.

2010-01-01

35

Shift in the hepatitis B virus genotype distribution in the last decade among the HBV carriers from eastern India: possible effects on the disease status and HBV epidemiology.  

PubMed

In a previous study from eastern India, the prevalence of HBV/C has been increasing among the blood donors. In order to analyze whether there has been any shift in HBV genotype distributions in recent years, the HBV genotypes prevalent during the periods 2000-2002 (Group-I; n=176) and 2007-2009 (Group-II; n=203) were compared, with special attention to changes in the proportion of HBV/C. The rate of prevalence of the three HBV genotypes (A, C, and D; percent prevalence 19.9/21.6/58.5 in Group-I vs. 31.0/28.6/40.4 in Group-II) underwent significant changes with increases in HBV/A and HBV/C among the HBV carriers (0.002). Among the asymptomatic carriers, the prevalence of these two genotypes (P=0.021 for HBV/A and P=0.005 for HBV/C) was significantly high. A notable increase was also observed among the chronic liver disease cases. HBV/A increased significantly among the older age Groups (? 51 years), whereas the increase of HBV/C was significant among the younger age Groups (? 20 years). With the increase of HBV/A and HBV/C, the rates of basal core promoter double mutation (1762T/1764A) also increased considerably. Binary logistic regression analysis revealed that both HBV/A and 1762T/1764A mutations are predictors of chronic liver disease state over asymptomatic carrier state. Thus, this study highlights the possible influence of HBV genotype shift on the changing scenario of HBV epidemiology and disease in the population. PMID:23765773

Biswas, Avik; Panigrahi, Rajesh; Pal, Manisha; Chakraborty, Subhasis; Bhattacharya, Prasun; Chakrabarti, Shekhar; Chakravarty, Runu

2013-08-01

36

Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees.  

PubMed

Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen (HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1.41 and 19.79.5 are of the IgG1 isotype and have high affinity constants for HBsAg binding in the range of 10(-10) mol/L. Monoclonal antibody 17.1.41 recognizes a conformational epitope on the a determinant of HBsAg whereas mAb 19.79.5 recognizes a linear one. The 2 mAbs bind to a panel of hepatitis B virus (HBV) subtypes with distinct patterns. The neutralizing activity of these antibodies was tested in 2 different animal model systems. Administration of each mAb to HBV-Trimera mice, a system that provides a mouse model for human hepatitis B infection, reduced the viral load and the percentage of HBV-DNA-positive mice in a dose-dependent manner. These 2 mAbs were more effective than a polyclonal antibody preparation (Hepatect; Biotest Pharma, Dreieich, Germany) in both inhibition of HBV liver infection and reduction of viral load. A single administration of a mixture of these mAbs into HBV chronic carrier chimpanzees resulted in immediate reduction in HBsAg levels followed by recurrence to initial levels within few days. Thus, these mAbs may be potential candidates for preventive therapy or in combination with other antiviral agents against HBV. Further studies in humans are needed to assess these mAbs in various clinical indications. PMID:10960454

Eren, R; Ilan, E; Nussbaum, O; Lubin, I; Terkieltaub, D; Arazi, Y; Ben-Moshe, O; Kitchinzky, A; Berr, S; Gopher, J; Zauberman, A; Galun, E; Shouval, D; Daudi, N; Eid, A; Jurim, O; Magnius, L O; Hammas, B; Reisner, Y; Dagan, S

2000-09-01

37

Identification of a new hepatitis B virus (HBV) genotype from Brazil that expresses HBV surface antigen subtype adw4  

Microsoft Academic Search

The complete genome of a hepatitis B virus (HBV) from Brazil that expressed the subtype adw4 of HBV surface antigen (HBsAg) was cloned and sequenced. The genome, termed w4B, consists of 3215 bp. The overall genetic organization of typical hepadnaviruses with four open reading frames including the preC region was found to be conserved. When comparing the w4B sequence with

Heike Naumann; Stephan Schaefer; C. F. T. Yoshida; A. M. C. Gaspar; R. Repp; W. H. Gerlich

1993-01-01

38

Successful allogeneic bone marrow transplantation from an HBV-positive donor into an HBV-positive recipient using lamivudine  

Microsoft Academic Search

A 21-year-old woman with severe aplastic anemia underwent allogeneic bone marrow transplantation from an HLA-identical sibling donor. The patient also had chronic hepatitis B and the donor was an HBV carrier. To decrease HBV and improve hepatic dysfunction before BMT, the patient had received lamivudine for 6 months. After marrow transfusion, administration of lamivudine was continued to inhibit replication of

S Hashino; M Takahata; A Nozawa; K Izumiyama; K Chiba; S Suzuki; S Hige; M Asaka

2002-01-01

39

Hepatitis B virus (HBV) induces the expression of interleukin-8 that in turn reduces HBV sensitivity to interferon-alpha.  

PubMed

High levels of serum interleukin-8 (IL-8) have been detected in chronic hepatitis B (CHB) patients during episodes of hepatitis flares. We investigated whether hepatitis B virus (HBV) may directly induce IL-8 production and whether IL-8 may antagonize interferon-alpha (IFN-?) antiviral activity against HBV. We showed that CHB patients had significantly higher IL-8 levels both in serum and in liver tissue than controls. In HBV-replicating HepG2 cells, IL-8 transcription was significantly activated. AP-1, C/EBP and NF-kB transcription factors were concurrently necessary for maximum IL-8 induction. Moreover, HBx viral protein was recruited onto the IL-8 promoter and this was paralleled by IL8-bound histone hyperacetylation and by active recruitment of transcriptional coactivators. Inhibition of IL-8 increases the antiviral activity of IFN-? against HBV. Our results indicate that HBV activates IL-8 gene expression by targeting the epigenetic regulation of the IL-8 promoter and that IL-8 may contribute to reduce HBV sensitivity to IFN-?. PMID:23890815

Pollicino, Teresa; Bellinghieri, Luigi; Restuccia, Agnese; Raffa, Giuseppina; Musolino, Cristina; Alibrandi, Angela; Teti, Diana; Raimondo, Giovanni

2013-09-01

40

HCV and HBV coexist in HBsAg-negative patients with HCV viremia; possibility of coinfection in these patients must be considered in HBV-high endemic area.  

National Technical Information Service (NTIS)

Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with HBV infection in Korea. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfe...

D. S. Lee

1998-01-01

41

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

PubMed Central

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.

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

42

Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1?  

PubMed Central

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 1? (HNF1?) mRNA, a negative regulator of HBV Enhancer I, to attenuate HNF1? 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 HNF1?, 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.

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

43

Inhibition of hepatitis B virus (HBV) gene expression and replication by HBx gene silencing in a hydrodynamic injection mouse model with a new clone of HBV genotype B  

PubMed Central

Background It has been suggested that different hepatitis B virus (HBV) genotypes may have distinct virological characteristics that correlate with clinical outcomes during antiviral therapy and the natural course of infection. Hydrodynamic injection (HI) of HBV in the mouse model is a useful tool for study of HBV replication in vivo. However, only HBV genotype A has been used for studies with HI. Methods We constructed 3 replication-competent clones containing 1.1, 1.2 and 1.3 fold overlength of a HBV genotype B genome and tested them both in vitro and in vivo. Moreover, A HBV genotype B clone based on the pAAV-MCS vector was constructed with the 1.3 fold HBV genome, resulting in the plasmid pAAV-HBV1.3B and tested by HI in C57BL/6 mice. Application of siRNA against HBx gene was tested in HBV genotype B HI mouse model. Results The 1.3 fold HBV clone showed higher replication and gene expression than the 1.1 and 1.2 fold HBV clones. Compared with pAAV-HBV1.2 (genotype A), the mice HI with pAAV-HBV1.3B showed higher HBsAg and HBeAg expression as well as HBV DNA replication level but a higher clearance rate. Application of two plasmids pSB-HBxi285 and pSR-HBxi285 expressing a small/short interfering RNA (siRNA) to the HBx gene in HBV genotype B HI mouse model, leading to an inhibition of HBV gene expression and replication. However, HBV gene expression may resume in some mice despite an initial delay, suggesting that transient suppression of HBV replication by siRNA may be insufficient to prevent viral spread, particularly if the gene silencing is not highly effective. Conclusions Taken together, the HI mouse model with a HBV genotype B genome was successfully established and showed different characteristics in vivo compared with the genotype A genome. The effectiveness of gene silencing against HBx gene determines whether HBV replication may be sustainably inhibited by siRNA in vivo.

2013-01-01

44

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

PubMed Central

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.

2011-01-01

45

An overview of molecular epidemiology of hepatitis B virus (HBV) in India  

PubMed Central

Hepatitis B virus (HBV) is one of the major global public health problems. In India, HBsAg prevalence among general population ranges from 2% to 8%, placing India in intermediate HBV endemicity zone and the number of HBV carriers is estimated to be 50 million, forming the second largest global pool of chronic HBV infections. India is a vast country, comprised of multiracial communities with wide variations in ethnicity and cultural patterns, which is attributable to its geographical location, gene influx due to invasion and/or anthropological migrations in the past. Moreover, recent increase in trade, trafficking and use of illicit drugs has also considerably influenced the epidemiology of HBV, specifically in the eastern and north eastern parts of India. However, data on the molecular epidemiology of HBV in India is scanty. HBV genotypes A and D have been well documented from different parts of mainland India. Interestingly, in addition to genotypes A and D, genotype C having high nucleotide similarity with south East Asian subgenotype Cs/C1 strain, have been detected exclusively from eastern Indian HBV carriers, suggesting a recent introduction. Thus, compared to other parts of India, the molecular epidemiology of HBV is naturally distinct in eastern India. Very recently, taking the advantage of circulation of three distinct HBV genotypes within the population of eastern India, different aspects of HBV molecular epidemiology was studied that revealed very interesting results. In this study, the clinical significance of HBV genotypes, core promoter and precore mutations, possible routes of introduction of HBV genotype C in eastern India, the clinical implications of x gene variability, prevalence of the AFB1 induced p53 gene codon 249 mutation, the transmission potentiality of HBV among asymptomatic/inactive or occult HBV carriers and the genetic variability of HBV persisting in the PBL was investigated. In this manuscript, the information available on the molecular epidemiology of HBV in India has been reviewed and the results of studies among the eastern Indian population have been summarised.

Datta, Sibnarayan

2008-01-01

46

Hepatitis B surface antigen seroconversion after HBV reactivation in non-Hodgkin's lymphoma  

PubMed Central

Reactivation of hepatitis B virus (HBV) can occur in lymphoma patients infected with HBV when they receive chemotherapy or immunotherapy. Prophylactic administration of lamivudine (LAM) reduces the morbidity and mortality associated with HBV reactivation. However, what defines HBV reactivation and the optimal duration of treatment with LAM have not yet been clearly established. HBV reactivation may occur due to the cessation of prophylactic LAM, although re-treatment with nucleoside analogs may sometimes result in hepatitis B surface antigen (HBsAg) seroconversion, which is a satisfactory endpoint for the management of HBV infection. We report a case of HBV reactivation in a 68-year-old HBsAg-positive patient who received rituximab-based immunochemotherapy for follicular lymphoma. HBV reactivation developed following cessation of prophylactic LAM therapy. The patient subsequently received treatment with entecavir (ETV), which led to a rapid and sustained suppression of HBV replication and HBsAg seroconversion. We also appraised the literature concerning HBV reactivation and the role of ETV in the management of HBV reactivation in lymphoma patients. A total of 28 cases of HBV reactivation have been reported as having been treated with ETV during or after immunosuppressive chemotherapy in lymphoma patients. We conclude that ETV is an efficacious and safe treatment for HBV reactivation following LAM cessation in lymphoma patients treated with rituximab-based immunochemotherapy.

Liu, Wei-Ping; Zheng, Wen; Song, Yu-Qin; Ping, Ling-Yan; Wang, Gui-Qiang; Zhu, Jun

2014-01-01

47

Hepatitis B surface antigen seroconversion after HBV reactivation in non-Hodgkin's lymphoma.  

PubMed

Reactivation of hepatitis B virus (HBV) can occur in lymphoma patients infected with HBV when they receive chemotherapy or immunotherapy. Prophylactic administration of lamivudine (LAM) reduces the morbidity and mortality associated with HBV reactivation. However, what defines HBV reactivation and the optimal duration of treatment with LAM have not yet been clearly established. HBV reactivation may occur due to the cessation of prophylactic LAM, although re-treatment with nucleoside analogs may sometimes result in hepatitis B surface antigen (HBsAg) seroconversion, which is a satisfactory endpoint for the management of HBV infection. We report a case of HBV reactivation in a 68-year-old HBsAg-positive patient who received rituximab-based immunochemotherapy for follicular lymphoma. HBV reactivation developed following cessation of prophylactic LAM therapy. The patient subsequently received treatment with entecavir (ETV), which led to a rapid and sustained suppression of HBV replication and HBsAg seroconversion. We also appraised the literature concerning HBV reactivation and the role of ETV in the management of HBV reactivation in lymphoma patients. A total of 28 cases of HBV reactivation have been reported as having been treated with ETV during or after immunosuppressive chemotherapy in lymphoma patients. We conclude that ETV is an efficacious and safe treatment for HBV reactivation following LAM cessation in lymphoma patients treated with rituximab-based immunochemotherapy. PMID:24803836

Liu, Wei-Ping; Zheng, Wen; Song, Yu-Qin; Ping, Ling-Yan; Wang, Gui-Qiang; Zhu, Jun

2014-05-01

48

Evaluation of salivary beta-2 microglobulin as HBV proliferation marker in HBS Ag+, HBV DNA PCR+ and HBV DNA PCR? subjects  

PubMed Central

Aim The aim of this study was to determine the concentration of salivary B2M as a marker of viral proliferation in HBS Ag+, HBV DNA PCR+ and Hbs Ag+ and HBV DNA PCR? subjects. Background Beta-2 microglobulin (B2M) is responsible for transmission of viral antigens such as Hepatitis B (HBV) on the surface of liver cells as part of an HLA complex. Patients and methods In this case control study, 25 PCR+ and 2 PCR? patients were included. 5 mL of the saliva sample was obtained from all patients and salivary B2M level was measured using nephelometer. The data was evaluated by the descriptive, chi square and t tests. Results 72% of the PCR+ patients received medications and in contrast, 85.7% of the patients with PCR? did not take any medication (P < 0.001). The average salivary concentration ofBeta-2 microglobulin in the PCR+ group (5.28 ± 5.45 mg/deciliter) was more than PCR? group (1.51±0.77) and this difference was statistically significant (P = 0.003). Conclusion The salivary B2Mlevel can be used as a marker of viral proliferation in patients with hepatitis B.

Abdolsamadi, Hamidreza; Eini, Peiman; Kaboli, Seyed Alireza; Hajilooei, Mehrdad; MoghimBeigi, Abbas; Davoudi, Poorandokht; AhmadiMotemayel, Fatemeh; Shalmani, Hamid Mohaghegh

2013-01-01

49

Hepatitis B surface antigen-negative, but HBV DNA-positive patients in Bangladesh.  

PubMed

Hepatitis B surface antigen (HBsAg) is regarded as sole marker of hepatitis B virus (HBV) infection in Bangladesh and most other developing countries. However, some HBV-negative subjects may harbor HBV DNA and transfusion of their blood may cause HBV infection in recipients. HBV DNA was checked in 20 patients with cryptogenic liver cirrhosis, 10 patients with hepatocellular carcinoma without any known etiology, and 10 apparently healthy subjects with elevated levels of serum alanine aminotransferase (ALT). HBV DNA was detected in 8 of 20 patients with cryptogenic liver cirrhosis, 1 of 10 patients with hepatocellular carcinoma, and 2 of 10 apparent healthy subjects with elevated ALT. However, all of them were negative for HBsAg in the sera. This study indicates that some additional mechanisms should be developed for detection of HBsAg-negative HBV-infected subjects for efficient control and management of HBV infection in Bangladesh. PMID:23540186

Mahtab, M A; Akbar, S M F; Rahman, S

2012-12-01

50

Associations of pesticides, HCV, HBV, and hepatocellular carcinoma in Egypt  

Microsoft Academic Search

The rate of hepatocellular carcinoma (HCC) is increasing in Egypt where the major risk factors are chronic infections with hepatitis B and C viruses (HBV and HCV). A major segment of the population is employed in agriculture, raising the possibility that exposure to pesticides is an additional risk factor for HCC. The objective of this study is to investigate pesticides

Sameera Ezzat; Mohamed Abdel-Hamid; Soheir Abdel-Latif Eissa; Nadia Mokhtar; Nargis Albert Labib; Laila El-Ghorory; Nabiel Nasmi Mikhail; Amany Abdel-Hamid; Tamer Hifnawy; G. Thomas Strickland; Christopher A. Loffredo

2005-01-01

51

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

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.

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

2013-01-01

52

Investigations into the performance of various HBV physical structures for high efficiency harmonic generation  

Microsoft Academic Search

Heterostructure barrier varactors (HBV) with different physical structures have been investigated and characterised for their capacitance-voltage characteristic and device series resistance. This is a novel concept to increase the HBV capacitance modulation whilst minimize the device series resistance for the NLTL in achieving optimum harmonic generation. Various capacitance modulation characteristics can be engineered by shaping the HBV mesa with either

W. H. Chow; D. P. Steenson

2003-01-01

53

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

PubMed Central

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 HBc? 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-?) production profile.

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

2010-01-01

54

trans-Complementation of HBV rtM204I mutant replication by HBV wild-type polymerase  

PubMed Central

The function of the hepatitis B virus (HBV) wild-type (WT) polymerase (pol) expressed alone or in the context of the intact genome when interacting with HBV rtM204I in HepG2 cells was compared. We show that WT pol expression from a packaging-defective RNA can complement defective rtM204I pol activity resulting in increased levels of HBV replicative intermediates (RI). Analysis of the genetically marked genomes showed that this restoration resulted from trans-complementation, rather than recombination. In contrast, we demonstrate that enhanced levels of total HBV RI observed when cells were cotransduced with both WT and rtM204I baculoviruses were predominantly WT RI. In this case, WT pol was produced from a full-length pregenomic RNA (pgRNA). We conclude that the WT pol has the capacity to trans-complement the replication defect of rtM204I; however, when expressed from an authentic pgRNA, in a mixed infection, WT pol may not trans-complement efficiently.

Heipertz, Richard A.; Starkey, Jason L.; Miller, Thomas G.; Hu, Jianming; Isom, Harriet C.

2013-01-01

55

Chemotherapy-induced hepatitis B reactivation in lymphoma patients with resolved HBV infection: A prospective study.  

PubMed

Fatal hepatitis B virus (HBV) reactivation in lymphoma patients with "resolved" HBV infection (hepatitis B surface antigen [HBsAg] negative and hepatitis B core antibody [anti-HBc] positive) can occur, but the true incidence and severity remain unclear. From June 2009 to December 2011, 150 newly diagnosed lymphoma patients with resolved HBV infection who were to receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-based chemotherapy were prospectively followed. HBV DNA was checked at baseline, at the start of each cycle of chemotherapy, and every 4 weeks for 1 year after completion of rituximab-CHOP chemotherapy. Patients with documented HBV reactivation were treated with entecavir at a dosage of 0.5 mg/day for 48 weeks. HBV reactivation was defined as a greater than 10-fold increase in HBV DNA, compared with previous nadir levels, and hepatitis flare was defined as a greater than 3-fold increase in alanine aminotransferase (ALT) that exceeded 100 IU/L. Incidence of HBV reactivation and HBV-related hepatitis flares was 10.4 and 6.4 per 100 person-year, respectively. Severe HBV-related hepatitis (ALT >10-fold of upper limit of normal) occurred in 4 patients, despite entecavir treatment. Patients with hepatitis flare exhibited significantly higher incidence of reappearance of HBsAg after HBV reactivation (100% vs. 28.5%; P?=?0.003). Conclusion: In lymphoma patients with resolved HBV infections, chemotherapy-induced HBV reactivation is not uncommon, but can be managed with regular monitoring of HBV DNA and prompt antiviral therapy. Serological breakthrough (i.e., reappearance of HBsAg) is the most important predictor of HBV-related hepatitis flare. (Hepatology 2014;59:2092-2100). PMID:24002804

Hsu, Chiun; Tsou, Hsiao-Hui; Lin, Shyh-Jer; Wang, Ming-Chung; Yao, Ming; Hwang, Wen-Li; Kao, Woei-Yau; Chiu, Chang-Fang; Lin, Sheng-Fung; Lin, Johnson; Chang, Cheng-Shyong; Tien, Hwei-Fang; Liu, Tsang-Wu; Chen, Pei-Jer; Cheng, Ann-Lii

2014-06-01

56

Emergence of HBV resistance to lamivudine (3TC) in HIV/HBV co-infected patients in The Gambia, West Africa  

PubMed Central

Background Lamivudine (3TC) is a potent inhibitor of both Hepatitis B virus (HBV) and Human Immunodeficiency Virus (HIV) replication and is part of first-line highly active antiretroviral therapy (HAART) in the Gambia. Unfortunately, the effectiveness of 3TC against HBV is limited by the emergence of resistant strains. Aim The aim of this retrospective study was to characterise 3TC-resistant mutations in HBV from co-infected patients receiving HAART, by generating HBV polymerase sequence data and viral loads from HBV genotype E infected patients, both at initiation and during a course of 3TC therapy. Method Samples from 21 HBV chronic carriers co-infected with HIV-1 (n = 18), HIV-2 (n = 2) and HIV-dual (n = 1) receiving HAART for a period of 6-52 months were analysed for the emergence of 3TC-resistance mutations. Findings Sixteen out of 21 HBV/HIV co-infected patients responded well to HAART treatment maintaining suppression of HBV viraemia to low (? 104 copies/mL) (n = 5) or undetectable levels (< 260 copies/ml) (n = 11). Out of the 5 non-responders, 3 had developed 3TC-resistant HBV strains showing mutations in the YMDD motif at position 204 of the RT domain of the HBV polymerase. One patient showed the M204V+ L180M+ V173L+ triple mutation associated with a vaccine escape phenotype, which could be of public health concern in a country with a national HBV vaccination programme. All except one patient was infected with HBV genotype E. Conclusions Our findings confirm the risk of 3TC mutations in HAART patients following monotherapy. This is a novel study on 3TC resistance in HBV genotype E patients and encourage the use of tenofovir (in association with 3TC), which has not shown unequivocally documented HBV resistance to date, as part of first-line therapy in HIV/HBV co-infected patients in West Africa. HBV- hepatitis B infection; HIV- human immunodeficiency virus; HAART- antiretroviral therapy.

2011-01-01

57

Pro2Net  

NSDL National Science Digital Library

Formerly AccountingNet.com (see the June 18, 1998 Scout Report for Business and Economics), Pro2Net has been redesigned and expanded to offer its services to human resources, insurance, and legal professionals, as well as those who work in financial services. Pro2Net has fourteen main services, including Newsline, Career Center, Professional Education, and Link Library. Each category is broken into the four professions served by Pro2Net. The "Pro2Net Family of Sites" includes the Website's additional pages which offer a variety of new information in accounting, law, HR, and financial resources.

2007-06-07

58

SOCS3 expression correlates with severity of inflammation in mouse hepatitis virus strain 3-induced acute liver failure and HBV-ACLF.  

PubMed

Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immunohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1?, IL-6, and tumor necrosis factor (TNF)-?, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF. PMID:24939297

Li, Yong; Han, Mei-Fang; Li, Wei-Na; Shi, Ai-Chao; Zhang, Yuan-Ya; Wang, Hong-Yan; Wang, Fa-Xi; Li, Lan; Wu, Ting; Ding, Lin; Chen, Tao; Yan, Wei-Ming; Luo, Xiao-Ping; Ning, Qin

2014-06-01

59

Comparison of detection and quantification of HBV DNA in chronic HBeAg negative and positive patients by Abbott RealTime HBV and Roche Cobas TaqMan HBV assays.  

PubMed

Monitoring the serum hepatitis B viral DNA levels with sensitive realtime PCR assays is strongly recommended for the management of patients with chronic HBV infection. This study compares the performance of two realtime HBV quantitative PCR assays with samples from chronic HBeAg(+) and HBeAg(-) patients. PMID:23835030

Morris, Carol J; Hill, Mary; de Medina, Maria; Herman, Christine; Cloherty, Gavin A; Martin, Paul

2013-11-01

60

Expression and immunoreactivity of HCV\\/HBV epitopes  

Microsoft Academic Search

AIM: To develop the epitope-based vaccines to prevent Hepatitis C virus (HCV) \\/ Hepatitis B virus (HBV) infections. METHODS: The HCV core epitopes C1 STNPKPQRKTKRNTNRRPQD (residuals aa2-21) and C2 VKFPGGGQIVGGVYLLPRR (residuals aa22-40), envelope epitope E GHRMAWDMMMNWSP (residuals aa315-328) and HBsAg epitope S CTTPAQGNSMFPSCCCTKPTDGNC (residuals aa124-147) were displayed in five different sites of the flock house virus capsid protein as a

Xin-Yu Xiong; Xiao Liu; Yuan-Ding Chen

61

Republished paper: Managing HBV in patients with impaired immunity  

Microsoft Academic Search

Chronic hepatitis B is one of the most common infectious diseases worldwide. In patients with an impaired immune system the prevalence of HBsAg is even higher and the course of hepatitis B infection is often aggravated. In HIV\\/HBV co-infected patients, liver related morbidity and mortality can be reduced by implementing highly active antiretroviral treatment (HAART) that contains substances active against

Karsten Wursthorn; Heiner Wedemeyer; Michael P Manns

2010-01-01

62

Evaluation of the Abbott HBV RUO sequencing assay combined with laboratory-modified interpretive software.  

PubMed

The Abbott HBV RUO Sequencing assay (Abbott Molecular Inc., Des Plaines, IL), which combines automated sample processing, real-time PCR, and bidirectional DNA sequencing, was evaluated for detection of nucleos(t)ide analogue (NA) resistance-associated mutations located in the hepatitis B virus (HBV) polymerase (Pol) gene. Interpretive software from the assay manufacturer was modified to allow interrogation of the overlapping HBV surface (S) gene sequence for HBV genotype determination and detection of immune escape mutations. Analytical sensitivity (detection and sequencing) of the assay was determined to be 103.9 IU/ml (95% confidence interval [CI], 80.0 to 173.3) for HBV genotype A. Testing of commercially available HBV genotype panels consisting of 23 individual members yielded complete agreement between expected results and results obtained from the laboratory-developed HBV genotype library. Excellent specificity was observed among clinical specimens with serologic or molecular markers for various unrelated blood-borne viruses (n = 6) and sera obtained from healthy, HBV-negative blood donors (n = 20). Retrospectively selected clinical specimens tested by a commercial reference laboratory HBV sequencing assay (n = 54) or the Trugene HBV Genotyping kit (n = 7) and the Abbott HBV RUO Sequencing assay showed minor differences in detection and reporting of NA resistance-associated mutations in 7 of 61 (11.5%) specimens but complete agreement of genotype results. The Abbott HBV RUO Sequencing assay provided a convenient and efficient assay workflow suitable for routine clinical laboratory use, with the flexibility to be modified for customized detection of NA resistance-associated mutations, HBV genotype determination, and detection of immune escape mutations from a single contiguous HBV sequence. PMID:23100352

Germer, Jeffrey J; Abraham, Priya; Mandrekar, Jayawant N; Yao, Joseph D C

2013-01-01

63

Project ProMED.  

National Technical Information Service (NTIS)

The results of Project ProMED clearly demonstrated the potential usefulness of Personal Digital Assistants (PDAs), in particular, Apple's Newton MessagePad, in the health care environment of military medical centers. ProMED proved that PDA technology prov...

R. R. Whitecotton

1995-01-01

64

Occult HBV Infection: A Faceless Enemy in Liver Cancer Development  

PubMed Central

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.

Morales-Romero, Jaime; Vargas, Gustavo; Garcia-Roman, Rebeca

2014-01-01

65

False-Negative Hepatitis B Virus (HBV) Surface Antigen in a Vaccinated Dialysis Patient with a High Level of HBV DNA in the United States  

PubMed Central

Screening with hepatitis B surface antigen (HBsAg) is highly recommended for at-risk individuals. Mutations in the HBsAg can result in an inability to detect the virus during routine screening. We describe a hemodialysis patient found to have high levels of hepatitis B virus (HBV) DNA and HBV antibody but negative HBsAg on two routine assays.

Foy, Matthew C.; Thio, Chloe L.; Hwang, Hyon S.; Saulynas, Melissa; Hamilton, James P.; Fine, Derek M.

2012-01-01

66

Long-Term Hepatitis B Virus (HBV) Response to Lamivudine-Containing Highly Active Antiretroviral Therapy in HIV-HBV Co-Infected Patients in Thailand  

PubMed Central

Background Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV). In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART) and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known. Methodology/Principal Finding HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030) and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg). At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log10 IU/mL and 4.47 log10 copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24%) lost HBsAg and 7 of 8 (88%) HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months). HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L. Conclusions All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for the management of co-infected patients in resource-limited countries where the vast majority of co-infected patients are currently receiving 3TC.

Khamduang, Woottichai; Gaudy-Graffin, Catherine; Ngo-Giang-Huong, Nicole; Jourdain, Gonzague; Moreau, Alain; Luekamlung, Nuananong; Halue, Guttiga; Buranawanitchakorn, Yuwadee; Kunkongkapan, Sura; Buranabanjasatean, Sudanee; Lallemant, Marc; Sirirungsi, Wasna; Goudeau, Alain

2012-01-01

67

ProSound News  

NSDL National Science Digital Library

ProSound News is an online source for news and information in all facets of the recording industry. News articles are added frequently throughout each business day. In addition to providing appropriate news coverage, the site also features classifieds and an industry calendar. The archives of their news section contains news dating back to 2003. ProSound News is a service of United Entertainment Media.

2006-11-27

68

Distribution of HBV genotypes, subgenotypes and HBsAg subtypes among chronically infected patients in Serbia  

Microsoft Academic Search

Summary  Hepatitis B virus (HBV) has been classified into eight genotypes (some of them further divided into two or more subgenotypes)\\u000a and nine HBsAg subtypes, distinctly distributed geographically. The aim of this study was to gain insight into the distribution\\u000a of HBV genotypes, subgenotypes and HBsAg subtypes among HBV chronically infected patients in Serbia, since there were no previously\\u000a published data

I. Lazarevic; M. Cupic; D. Delic; N. S. Svirtlih; J. Simonovic; T. Jovanovic

2007-01-01

69

High Prevalence of Human Parvovirus 4 Infection in HBV and HCV Infected Individuals in Shanghai  

PubMed Central

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.

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

2012-01-01

70

CRTC2 enhances HBV transcription and replication by inducing PGC1? expression  

PubMed Central

Background Hepatitis B virus (HBV) transcription and replication are essentially restricted to hepatocytes. Based on the HBV enhancer and promoter complex that links hepatic glucose metabolism to its transcription and replication, HBV adopts a regulatory system that is unique to the hepatic gluconeogenic genes. CRTC2, the CREB-regulated transcription coactivator 2, is a critical switch modulating the gluconeogenic program in response to both hormonal and intracellular signals. However, the relationship between CRTC2 and HBV transcription and replication remains unclear. Methods To analyze the influence of CRTC2 on HBV transcription and replication, CRTC2 expression construct or siRNA was cotransfected with plasmids containing enhancer II/core promoter complex-controlled luciferase or 1.3× wtHBV genome in Huh-7 cells. Luciferase activity, HBV core protein expression, HBV transcripts, and DNA replication intermediates were measured by luciferase assays, western blots, real-time polymerase chain reaction (PCR), and Southern blots, respectively. Forskolin (FSK) or phosphorylation-defective CRTC2 mutants were further utilized to elucidate the potential mechanism. siRNA against peroxisome proliferator-activated receptor-? coactivator 1? (PGC1?) was also used to examine the mediator involved in CRTC2-regulated HBV biosynthesis in Huh-7 cells. Results CRTC2 overexpression increased HBV transcription and replication in Huh-7 cells, including levels of core protein expression, mRNA, and DNA replication intermediates. Correspondingly, CRTC2 knock down by siRNA reduced HBV biosynthesis. FSK treatment strongly enhanced the effect of CRTC2 through triggering the dephosphorylation and nuclear entry of CRTC2. The phosphorylation-defective mutant (S171A/S275A) of CRTC2 localized in the nucleus and was constitutively active, which dramatically promoted HBV transcription and replication similar to FSK-treated wild-type CRTC2. Knock down of PGC1?, whose expression was induced by CRTC2, greatly compromised the enhancing effect of CRTC2 on HBV transcription and replication. Conclusions Our results clearly indicate that non-phosphorylated CRTC2 strongly enhances HBV biosynthesis through inducing PGC1? expression. Further study of the mechanisms will elucidate the importance of metabolic signals on HBV transcription and replication, and offer insight into potential targets for developing anti-HBV agents.

2014-01-01

71

High Seroprevalence of HBV and HCV Infection in HIV-Infected Adults in Kigali, Rwanda  

PubMed Central

Background Data on prevalence and incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in Rwanda are scarce. Methods HBV status was assessed at baseline and Month 12, and anti-HCV antibodies at baseline, in a prospective cohort study of HIV-infected patients in Kigali, Rwanda: 104 men and 114 women initiating antiretroviral therapy (ART) at baseline, and 200 women not yet eligible for ART. Results Baseline prevalence of active HBV infection (HBsAg positive), past or occult HBV infection (anti-HBc positive and HBsAg negative) and anti-HCV was 5.2%, 42.9%, and 5.7%, respectively. The active HBV incidence rate was 4.2/1,000 person years (PY). In a multivariable logistic regression model using baseline data, participants with WHO stage 3 or 4 HIV disease were 4.19 times (95% CI 1.21–14.47) more likely to have active HBV infection, and older patients were more likely to have evidence of past exposure to HBV (aRR 1.03 per year; 95%CI 1.01–1.06). Older age was also positively associated with having anti-HCV antibodies (aOR 1.09; 95%CI 1.04–1.14) while having a higher baseline HIV viral load was negatively associated with HCV (aOR 0.60; 95% CI 0.40–0.98). The median CD4 increase during the first 12 months of ART was lower for those with active HBV infection or anti-HCV at baseline. Almost all participants (88%) with active HBV infection who were on ART were receiving lamivudine monotherapy for HBV. Conclusion HBV and HCV are common in HIV-infected patients in Rwanda. Regular HBsAg screening is needed to ensure that HIV-HBV co-infected patients receive an HBV-active ART regimen, and the prevalence of occult HBV infection should be determined. Improved access to HBV vaccination is recommended. Active HCV prevalence and incidence should be investigated further to determine whether HCV RNA PCR testing should be introduced in Rwanda.

Rusine, John; Ondoa, Pascale; Asiimwe-Kateera, Brenda; Boer, Kimberly R.; Uwimana, Jean Marie; Mukabayire, Odette; Zaaijer, Hans; Mugabekazi, Julie; Reiss, Peter; van de Wijgert, Janneke H.

2013-01-01

72

Epigallocatechin gallate inhibits HBV DNA synthesis in a viral replication - inducible cell line  

PubMed Central

AIM: To analyze the antiviral mechanism of Epigallocatechin gallate (EGCG) against hepatitis B virus (HBV) replication. METHODS: In this research, the HBV-replicating cell line HepG2.117 was used to investigate the antiviral mechanism of EGCG. Cytotoxicity of EGCG was analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Hepatitis B virus e antigen (HBeAg) and hepatitis B virus surface antigen (HBsAg) in the supernatant were detected by enzyme-linked immunosorbent assay. Precore mRNA and pregenomic RNA (pgRNA) levels were determined by semi-quantitative reverse transcription polymerase chain reaction (PCR) assay. The effect of EGCG on HBV core promoter activity was measured by dual luciferase reporter assay. HBV covalently closed circular DNA and replicative intermediates of DNA were quantified by real-time PCR assay. RESULTS: When HepG2.117 cells were grown in the presence of EGCG, the expression of HBeAg was suppressed, however, the expression of HBsAg was not affected. HBV precore mRNA level was also down-regulated by EGCG, while the transcription of precore mRNA was not impaired. The synthesis of both HBV covalently closed circular DNA and replicative intermediates of DNA were reduced by EGCG treatment to a similar extent, however, HBV pgRNA transcripted from chromosome-integrated HBV genome was not affected by EGCG treatment, indicating that EGCG targets only replicative intermediates of DNA synthesis. CONCLUSION: In HepG2.117 cells, EGCG inhibits HBV replication by impairing HBV replicative intermediates of DNA synthesis and such inhibition results in reduced production of HBV covalently closed circular DNA.

He, Wei; Li, Li-Xia; Liao, Qing-Jiao; Liu, Chun-Lan; Chen, Xu-Lin

2011-01-01

73

False-negative hepatitis B virus (HBV) surface antigen in a vaccinated dialysis patient with a high level of HBV DNA in the United States.  

PubMed

Screening with hepatitis B surface antigen (HBsAg) is highly recommended for at-risk individuals. Mutations in the HBsAg can result in an inability to detect the virus during routine screening. We describe a hemodialysis patient found to have high levels of hepatitis B virus (HBV) DNA and HBV antibody but negative HBsAg on two routine assays. PMID:22441395

Foy, Matthew C; Thio, Chloe L; Hwang, Hyon S; Saulynas, Melissa; Hamilton, James P; Fine, Derek M; Atta, Mohamed G

2012-05-01

74

LINE(1)s of evidence in HBV-driven liver cancer.  

PubMed

Hepatitis B virus (HBV) integration in hepatocellular carcinoma (HCC) is a poorly understood event. In a recent Cancer Cell paper, Lau et al. (2014) describe a HBV-human fusion transcript (HBx-LINE1) that functions as a lncRNA, influences the epithelial-mesenchymal transition, and correlates with reduced patient survival and tumor formation in mice. PMID:24629329

Heikenwalder, Mathias; Protzer, Ulrike

2014-03-12

75

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

PubMed

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

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

2014-01-01

76

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

PubMed Central

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.

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

2014-01-01

77

Electroporation-mediated HBV DNA vaccination in primate models.  

PubMed

Electroporation has been shown to be an effective method to improve the efficiency of gene expression and the immunogenicity of DNA vaccines. To optimize the procedure and test for its efficacy in more clinically relevant large animal models, we studied the effects of electroporation-mediated DNA vaccination with different electro-pulse parameters in rhesus macaques. Plasmid DNA encoding the HBV preS2-S and an adjuvant plasmid encoding a fused gene of IL-2 and IFN-gamma were injected intramuscularly followed by electroporation once a month for several months. The humoral as well as cellular immune responses were closely followed for more than a year. The different electro-pulse parameters resulted in considerably different intensities in immune responses, suggesting that optimization of electroporation parameters is important in developing clinical application of DNA vaccination. PMID:18370224

Zhao, Yong-Gang; Xu, Yuhong

2008-01-01

78

Hepatitis B Surface Antigen Concentrations in Patients with HIV/HBV Co-Infection  

PubMed Central

HBsAg clearance is associated with clinical cure of chronic hepatitis B virus (HBV) infection. Quantification of HBsAg may help to predict HBsAg clearance during the natural course of HBV infection and during antiviral therapy. Most studies investigating quantitative HBsAg were performed in HBV mono-infected patients. However, the immune status is considered to be important for HBsAg decline and subsequent HBsAg loss. HIV co-infection unfavorably influences the course of chronic hepatitis B. In this cross-sectional study we investigated quantitative HBsAg in 173 HBV/HIV co-infected patients from 6 centers and evaluated the importance of immunodeficiency and antiretroviral therapy. We also compared 46 untreated HIV/HBV infected patients with 46 well-matched HBV mono-infected patients. HBsAg levels correlated with CD4 T-cell count and were higher in patients with more advanced HIV CDC stage. Patients on combination antiretroviral therapy (cART) including nucleos(t)ide analogues active against HBV demonstrated significant lower HBsAg levels compared to untreated patients. Importantly, HBsAg levels were significantly lower in patients who had a stronger increase between nadir CD4 and current CD4 T-cell count during cART. Untreated HIV/HBV patients demonstrated higher HBsAg levels than HBV mono-infected patients despite similar HBV DNA levels. In conclusion, HBsAg decline is dependent on an effective immune status. Restoration of CD4 T-cells during treatment with cART including nucleos(t)ide analogues seems to be important for HBsAg decrease and subsequent HBsAg loss.

Jaroszewicz, Jerzy; Reiberger, Thomas; Meyer-Olson, Dirk; Mauss, Stefan; Vogel, Martin; Ingiliz, Patrick; Payer, Berit Anna; Stoll, Matthias; Manns, Michael P.; Schmidt, Reinhold E.; Flisiak, Robert; Wedemeyer, Heiner; Peck-Radosavljevic, Markus; Rockstroh, Jurgen; Cornberg, Markus

2012-01-01

79

Evolutionary dynamics of HBV-D1 genotype epidemic in Turkey.  

PubMed

Hepatitis B virus (HBV), is the leading cause of liver diseases infecting an estimated 240 million persons worldwide. The HBV prevalence rates are variables between different countries, with an high level of endemicity in the south-eastern part of Europe. Seven main HBV-D subgenotypes have been described until now (D1-D7). Turkey, seems to have played an important role in the penetration of HBV-D1 in the Mediterranean area. The importance of Turkey in the European epidemiology of HBV is also suggested by the observation that the highest spread of HBV infection in the Continent are reported in Turkey with Romania, Bulgaria, Greece, Albania and some southern regions of Italy. In this paper the molecular epidemiology and the epidemiological history of HBV-D in Turkey was studied, by characterizing 34 new Turkish isolates and performing a phylogeographic reconstruction. By using a phylodynamic and phylogeographic Bayesian approach, the analysis suggested that HBV-D1 originated in Turkey about in the early 1940s. The large prevalence of D1 in comparison to the other subgenotypes in Turkey confirms the importance of this Country as epidemiological reservoir of HBV-D1 dispersion. The phylogeny suggests that after each initial introduction of the virus in a specific population, separate transmission clusters have been evolving along independent phylogenetic lineages. Better characterization and continuous monitoring of such groups are going to be crucial to understand in detail the epidemiology of HBV-D1 subgenotype in Turkey and to assess the efficacy of prevention, vaccination and therapy in controlling the epidemic. PMID:24243521

Ciccozzi, Massimo; Ciccaglione, Anna Rita; Lo Presti, Alessandra; Equestre, Michele; Cella, Eleonora; Ebranati, Erika; Gabanelli, Elena; Villano, Umbertina; Bruni, Roberto; Yalcinkaya, Tulay; Tanzi, Elisabetta; Zehender, Gianguglielmo

2014-01-01

80

Alpha/Beta Interferon Differentially Modulates the Clearance of Cytoplasmic Encapsidated Replication Intermediates and Nuclear Covalently Closed Circular Hepatitis B Virus (HBV) DNA from the Livers of Hepatocyte Nuclear Factor 1?-Null HBV Transgenic Mice†  

PubMed Central

Treatment with alpha interferon is a standard therapy for patients with chronic hepatitis B virus (HBV) infections. This treatment can reduce virus load and ameliorate disease symptoms. However, in the majority of cases, alpha interferon therapy fails to resolve the chronic HBV infection. The reason alpha interferon therapy is inefficient at resolving chronic HBV infections is assumed to be because it fails to eliminate covalently closed circular (CCC) HBV DNA from the nuclei of infected hepatocytes. In an attempt to address this issue, the stability of HBV CCC DNA in response to alpha/beta interferon induction was examined in HNF1?-null HBV transgenic mice. Alpha/beta interferon induction by polyinosinic-polycytidylic acid [poly(I-C)] treatment efficiently eliminated encapsidated cytoplasmic HBV replication intermediates while only modestly reducing nuclear HBV CCC DNA. These observations indicate that nuclear HBV CCC DNA is more stable than cytoplasmic replication intermediates in response to alpha/beta interferon induction. Consequently it appears that for therapies to resolve chronic HBV infection efficiently, they will have to target the elimination of the most stable HBV replication intermediate, nuclear HBV CCC DNA.

Anderson, Aimee L.; Banks, Krista E.; Pontoglio, Marco; Yaniv, Moshe; McLachlan, Alan

2005-01-01

81

Anti-HBV agents. Part 1: Synthesis of alisol A derivatives: A new class of hepatitis B virus inhibitors  

Microsoft Academic Search

A series of alisol A derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and cytotoxicities in vitro. The preliminary investigation demonstrates that simple modifications of the parent structure of alisol A can produce a number of potentially important derivatives against HBV. The most active anti-HBV compound 6a showed high activities against the secretion of HBV surface

Quan Zhang; Zhi-Yong Jiang; Jie Luo; Pi Cheng; Yun-Bao Ma; Xue-Mei Zhang; Feng-Xue Zhang; Jun Zhou; Ji-Jun Chen

2008-01-01

82

Mushroom lectin enhanced immunogenicity of HBV DNA vaccine in C57BL/6 and HBsAg-transgenic mice.  

PubMed

DNA vaccination is a promising strategy for activating immune responses against hepatitis B virus (HBV) infection. However, the accumulated data have shown that DNA vaccination alone generates weak immune responses. To enhance the immunogenicity of HBV DNA vaccine, lectin purified from pleurotus ostreatus (POL) was used as adjuvant of HBV DNA vaccine for C57BL/6 and HBV surface antigen transgenic (HBVsAg-Tg) mice. Our data demonstrate that low dose of POL (1 ?g/mouse) in conjunction with HBV DNA vaccine stimulated stronger HBV-specific delayed-type hypersensitivity (DTH) responses and higher HBV-specific IgG level than that in high dose of POL groups (5 ?g/mouse and 10 ?g/mouse). POL activated strong Th2 and Tc1 cell responses in immunized C57BL/6 and HBVsAg-Tg mice. POL as adjuvant of HBV DNA vaccine effectively enhanced HBV surface protein antibody (HBVsAb) and decreased HBVsAg level for HBV Tg mice treatment. Furthermore, POL infiltrated more lymphocytes excluding Th1, Th2 and Tc1 cell subtypes to liver of HBVsAg-Tg mice. Together, these results suggest that POL as adjuvant enhanced immunogenicity of HBV DNA vaccination and effectively stimulated immune reaponse for HBsAg-Tg mice treatment. Our findings implicate the potential of mushroom lectin as adjuvant of HBV DNA vaccine. PMID:23499522

Gao, Wenjuan; Sun, Yuhan; Chen, Shiwen; Zhang, Jingyao; Kang, Jingjing; Wang, Yongqiang; Wang, Hexiang; Xia, Guoliang; Liu, Qinghong; Kang, Youmin

2013-04-26

83

The inverse association of serum HBV DNA level with HDL and adiponectin in chronic hepatitis B infection  

Microsoft Academic Search

BACKGROUND: The natural history of hepatitis B virus (HBV) is complex and influenced by the level of viral replication and host factors. The hepatoprotective role of high density lipoproteins (HDL) and adiponectin as host factors on HBV persistence is less well understood. METHODS: To investigate correlation between HBV DNA level with clinical parameters in patients with chronic hepatitis B, 92

Ashraf Mohamadkhani; Kourosh Sayemiri; Reza Ghanbari; Elham Elahi; Hossein Poustchi; Ghodratollah Montazeri

2010-01-01

84

A type-specific nested PCR assay established and applied for investigation of HBV genotype and subgenotype in Chinese patients with chronic HBV infection  

PubMed Central

Background Many studies have suggested that hepatitis B virus (HBV) genotypes show not only geographical distribution and race specificity, but also are associated with disease progression and response to interferon treatment. The objective of this study was to develop a nested polymerase chain reaction (nPCR) assay for genotypes A-D and subgenotypes B1, B2, C1 and C2 of hepatitis B virus (HBV) and to investigate the distribution characteristics of HBV genotypes/subgenotype in China. Methods After redesigning the primers and optimizing the reaction conditions using common Taq polymerase, the sensitivity, specificity and reproducibility of the method were evaluated using plasmids and serum samples. In total, 642 serum samples from patients with chronic HBV infection were applied to investigate the distribution of HBV genotype and subgenotype in China. Results The genotype and subgenotype could be identified when the HBV DNA load of a sample was ?102.3?IU/mL. For the 639 successfully genotyped samples, the sequencing results of 130 randomly selected samples (20.3%, 130/639) were consistent with those of the nPCR method. The present study showed that HBV genotype B (11.2%, 72/642), C (68.2%, 438/642) and D (7.2%, 46/642) were circulating in China, while genotype C was the dominant strain except for western region where genotype D was the prevalent strain. The main subgenotypes of genotypes B and C were B2 (87.5%, 63/72) and C2 (92.9%, 407/438), respectively. Conclusions The low-cost nPCR method would be a useful tool for clinical and epidemiological investigation in the regions where genotypes A-D are predominant.

2012-01-01

85

Inhibition of hepatitis B virus (HBV) replication by pyrimidines bearing an acyclic moiety: effect on wild-type and mutant HBV.  

PubMed

Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. The main clinical limitation of a current antiviral drug for HBV, lamivudine, is the emergence of drug-resistant viral strains upon prolonged therapy. A group of 5-, 6-, or 5,6-substituted acyclic pyrimidine nucleosides with a 1-[(2-hydroxyethoxy)methyl] moiety were synthesized and evaluated for antiviral activities. The target compounds were prepared by the reaction of silylated uracils possessing a variety of substituents at the C-5 or C-6 positions or both with 1,3-dioxolane in the presence of potassium iodide and chlorotrimethylsilane by a convenient and single-step synthesis. Among the compounds tested, 5-chloro and 5-bromo analogues possessing an acyclic glycosyl moiety were the most effective and selective antiviral agents in the in vitro assays against wild-type duck HBV (EC50=0.4-2.2 and 3.7-18.5 microM, respectively) and human HBV-containing 2.2.15 cells (EC50=4.5-45.4 and 18.5-37.7 microM, respectively). These compounds were also found to retain sensitivity against lamivudine-resistant HBV containing a single mutation (M204I) and double mutations (L180M/M204V). The compounds investigated did not show cytotoxicity to host HepG2 and Vero cells, up to the highest concentration tested. The results presented here confirm and accentuate the potential of acyclic pyrimidine nucleosides as anti-HBV agents and extend our previous observations. We herein report the capability of acyclic pyrimidine nucleosides to inhibit the replication of both wild-type and drug-resistant mutant HBV. PMID:16539393

Semaine, Wassila; Johar, Monika; Tyrrell, D Lorne J; Kumar, Rakesh; Agrawal, B

2006-03-23

86

ProSoil  

NSDL National Science Digital Library

From the Food and Agricultural Organization of the United Nations comes the Problem Soils Database. The site gives general descriptions of problem soils, and the database, called ProSoil, can be used to search for literature sources that treat problem soils and to identify tables, figures, and case studies related to problem soils. The site and the database are well designed and easy to use, giving those users interested a handy tool for finding the facts they need.

2000-01-01

87

The med.pro domain.  

PubMed

The evolution of the Internet Domain Name System is summarized. The credentialing requirements with respect to licensure, board certification, and affiliations for obtaining a med.pro address are described. Security issues are discussed, and the mechanisms for obtaining a med.pro are delineated. The relative advantages and disadvantages of the med.pro domain are presented. PMID:14661426

Elliott, Brett

2003-10-01

88

Significance of PRO2000/ANCCA expression, a novel proliferation-associated protein in hepatocellular carcinoma  

PubMed Central

Background PRO2000/ANCCA may be an important candidate gene which located within a region of chromosome 8q in hepatocellular carcinoma (HCC). However, its significance remains unclear. The aim of this study was to explore the clinical significance of PRO2000/ANCCA expression in HCC. Methods The correlations of PRO2000/ANCCA expression with clinicopathological factors and prognosis of HCC patients were analyzed. Expression of PRO2000/ANCCA, ki-67, cyclinD1, p53 and p21 was detected in HCCs from 107 patients along with corresponding non-tumor tissues by immunohistochemistry. Results PRO2000/ANCCA expression was present in 66 of 107 (64.94%) HCC specimens in which 36 of 76 (47.37%) in well differentiated tumors and 30 of 31 (96.77%) in poorly differentiated tumors respectively, while 8 (7.48%) in adjacent non-tumor tissues with scattered positive cells. PRO2000/ANCCA expression was associated with clinicopathological features such as histological differentiation, number of tumor nodules, TNM stage, tumor microsatellite, portal vein tumor thrombus and recurrence, but not with gender, age, tumor size, cirrhosis, HBV infection and serum fetoprotein (AFP) level. There was a close relationship between PRO2000/ANCCA and ki-67 and cyclinD1 in HCC. PRO2000/ANCCA immunopositivity was independent of p53 and p21WAF1/Cip1. Conclusions Increased expression of PRO2000/ANCCA is associated with adverse outcome in patients with HCC and is a predictor of poor prognosis for HCC. PRO2000/ANCCA may be involved in the development of HCC and might promote cell proliferation through a p53/ P21WAF1/Cip1-independent pathway.

2014-01-01

89

Hospital Cluster of HBV Infection: Molecular Evidence of Patient-to-Patient Transmission through Lancing Device  

PubMed Central

Introduction In western countries the transmission of hepatitis B virus (HBV) transmission through multi-patients lancing devices has been inferred since early ‘90s, however no study has ever provided biological evidence which directly link these device with HBV cross-infection. Here we present results of an outbreak investigation which could associate, by molecular techniques, the use of lancing device on multiple patients with HBV transmission in an Italian oncohematology unit. Methods The outbreak investigation was designed as a retrospective cohort study to identify all potential cases. All cases identified were eventually confirmed through molecular epidemiology techniques. Audit of personnel including extensive review of infection control measures and reviewing personnel's tests for HBV was done identify transmission route. Results Between 4 May 2006 and 21 February 2007, six incident cases of HBV infection were reported among 162 patients admitted in the oncohematology. The subsequent molecular instigation proved that 3 out 6 incident cases and one prevalent cases (already infected with HBV at the admission) represented a monophyletic cluster of infection. The eventual environmental investigation found that an identical HBV viral strain was present on a multi-patients lancing device in use in the unit and the inferential analysis showed a statistically significant association between undergoing lancing procedures and the infection. Discussion This investigation provide molecular evidence to link a HBV infection cluster to multi-patients lancing device and highlights that patients undergoing capillary blood sampling by non-disposable lancing device may face an unacceptable increased risk of HBV infection. Therefore we believe that multi-patients lancing devices should be banned from healthcare settings and replace with disposable safety lancets that permanently retract to prevent the use of the same device on multiple patients. The use of non-disposable lancing devices should be restricted to individual use at patients' home.

Lanini, Simone; Garbuglia, Anna Rosa; Puro, Vincenzo; Solmone, Mariacarmela; Martini, Lorena; Arcese, William; Nanni Costa, Alessandro; Borgia, Piero; Piselli, Pierluca; Capobionchi, Maria Rosaria; Ippolito, Giuseppe

2012-01-01

90

Primary biliary cirrhosis in HBV and HCV patients: Clinical characteristics and outcome  

PubMed Central

AIM: To present the characteristics, management and outcome of patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infections concurrent with primary biliary cirrhosis (PBC). METHODS: Since January 2001 to September 2009, we retrospectively evaluated the medical records of all HBV (n = 1493) and HCV patients (n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC (8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC. RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients, while one third (5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV (56.1 ± 11.2 vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics (10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency (87.5% vs 33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up. CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.

Rigopoulou, Eirini I; Zachou, Kalliopi; Gatselis, Nikolaos K; Papadamou, Georgia; Koukoulis, George K; Dalekos, George N

2013-01-01

91

Preventing primary liver cancer: the HBV vaccination project in the Gambia (West Africa)  

PubMed Central

The Gambia Hepatitis Intervention Study (GHIS) consisted in the progressive introduction of HBV plasma-derived vaccine in different zones of this African country during the period 1986-1990. The study was launched and coordinated by IARC and is one of the most effective examples of an intervention project that both substantially contributed to our knowledge and to the health of local populations. Similar intervention studies have been carried out in South-East Asia. The studies indicate that the natural history of HBV infection differs in different populations , having a direct relevance for the implementation of HBV vaccination programmes in various parts of the world.

2011-01-01

92

Phage displayed HBV core antigen with immunogenic activity.  

PubMed

Hepatitis B is a major public health problem worldwide, which may lead to chronic liver diseases such as cirrhosis and hepatocellular carcinoma. The hepatitis B core antigen (HBcAg) is one of the major viral proteins, which forms the inner core of hepatitis B virus (HBV) particles. In this study, filamentous bacteriophage M13 was genetically modified to display the polypeptides of HBcAg in order to develop an alternative carrier system. HBcAg gene was inserted into the minor coat protein (pIII) gene of M13, and HBcAg was expressed on the phage surface as a whole protein. Antigenicity and immunogenicity of HBcAg were tested by immunizing BALB/c mice three times with HBcAg-displaying recombinant phages. After successful immunization, one of the mice with high antibody titer to HBcAg was selected for fusion, and four monoclonal antibodies specific for HBcAg were developed. This result showed that HBcAg-displaying recombinant bacteriophages are immunogenic and can potentially be used for the development of monoclonal antibodies. PMID:21915589

Bahadir, Aylin Ozdemir; Balcioglu, Bertan Koray; Uzyol, Kamil Serkan; Hatipoglu, Ibrahim; Sogut, Ibrahim; Basalp, Aynur; Erdag, Berrin

2011-12-01

93

ProVoc  

NSDL National Science Digital Library

Learning a new language can be daunting, but this handy application can make this process a bit friendlier. With ProVoc, users can download existing vocabulary sets for English, French, German, Italian, Spanish, Danish, and dozens of other languages. After that, they can run through these words at their leisure on their computer or their iPod for convenience. Finally, the site also includes a FAQ section that answers any number of topical questions about the application. This version is compatible with computers running Mac OS X 10.3 and newer.

2007-01-01

94

Characterization of HIV-HBV co-infection in a multi-national HIV-infected cohort  

PubMed Central

Objective To understand the HIV-hepatitis B virus (HBV) epidemic from a global perspective by clinically and virologically characterizing these viruses at the time of antiretroviral therapy (ART) initiation in a multi-national cohort. Methods and design HIV-infected subjects enrolled in two international studies were classified as HIV-HBV co-infected or HIV monoinfected prior to ART. HIV-HBV co-infected subjects were tested for HBV characteristics, hepatitis D virus (HDV), a novel non-invasive marker of liver disease, and drug-resistant HBV. Comparisons between discrete covariates used chi-square or Fisher’s exact tests (and Jonchkheere-Terpstra for trend tests) while continuous covariates were compared using Wilcoxon Rank-Sum Test. Results Of the 2105 HIV-infected subjects from 11 countries, the median age was 34 years and 63% were Black. The 115 HIV-HBV co-infected subjects had significantly higher ALT and AST values, lower body mass index, and lower CD4+ T-cell counts than HIV monoinfected subjects (median 159 cells/mL and 137 cells/mL, respectively, P=0.04). In the co-infected subjects, 49.6% had HBeAg-negative HBV, 60.2% had genotype A HBV, and 13% were HDV positive. Of the HBeAg-negative subjects, 66% had HBV DNA ?2000 IU/ml compared to 5.2% of the HBeAg-positive subjects. Drug-resistant HBV was not detected. Conclusions Screening for HBV in HIV-infected patients in resource-limited settings is important since it is associated with lower CD4+ T-cell counts. In settings where HBV DNA is not available, HBeAg may be useful to assess the need for HBV treatment. Screening for drug-resistant HBV is not needed prior to starting ART in settings where this study was conducted.

THIO, Chloe L.; SMEATON, Laura; SAULYNAS, Melissa; HWANG, Hyon; SARAVAN, Shanmugam; KULKARNI, Smita; HAKIM, James; NYIRENDA, Mulinda; IQBAL, Hussain Syed; LALLOO, Umesh G.; MEHTA, Anand S.; HOLLABAUGH, Kimberly; CAMPBELL, Thomas B.; LOCKMAN, Shahin; CURRIER, Judith S.

2013-01-01

95

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

ClinicalTrials.gov

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

2012-04-24

96

Management of hepatitis C in HIV and/or HBV co-infected patients.  

PubMed

Co-infection with either HIV or HBV in chronic hepatitis C patients is common, since all these viruses share transmission routes and geographical distribution. Interaction between these viruses generally amplifies liver damage, increasing the risk of developing end-stage liver disease and hepatocellular carcinoma. HIV-HCV co-infection is associated with poorer response to antiviral therapy. New antivirals against HCV are eagerly awaited for this population. HBV-HCV dual infections are less common. The principles guiding indication of therapy in monoinfected patients should be followed considering which virus replicates in persons with serological markers of dual HBV-HCV infection. Although there is growing evidence supporting the use of direct acting antivirals (DAA) in dually infected patients with active HCV replication, prospective trials should be conducted to demonstrate their benefit, assessing carefully the rate and clinical consequences of HBV rebounds. PMID:23199509

Fernández-Montero, José Vicente; Soriano, Vicente

2012-08-01

97

HBV infection in HIV-infected subjects in the state of Piauí, Northeast Brazil.  

PubMed

In this study, the prevalence, genotype frequency, and risk factors for HBV infection in 768 HIV-infected subjects living in Piauí were determined. Forty-six (6.0 %) HIV-positive subjects were reactive for HBsAg and positive for HBV-DNA. Genotypes A (71.8 %), F (23.9 %) and D (4.3 %) were identified. Multivariate analysis revealed an association between HIV-HBV coinfection and male gender, older age groups, unprotected sex, reporting more than ten sexual partners throughout life, STD, and tattooing. This study shows the importance of monitoring sites and professionals who perform tattooing and practice safe sex to prevent the spread of HIV and HBV infections. PMID:24264385

Oliveira, Evaldo H; Lima Verde, Roseane M C; Pinheiro, Luiz Marcelo L; Benchimol, Marcos G; Aragão, Ana Luisa E D; Lemos, José Alexandre R; Oliveira-Filho, Aldemir B; Vallinoto, Antonio C R

2014-05-01

98

Liver microRNA hsa-miR-125a-5p in HBV Chronic Infection: Correlation with HBV Replication and Disease Progression  

PubMed Central

To study in HBsAg chronic carriers the expression of liver hsa-miR-125a-5p and its correlation with liver HBV-DNA values and clinical presentation, 27 consecutive Caucasian, HBsAg/anti-HBe/HBV-DNA-positive patients who were naive to nucleos(t)ide analogues and interferon therapy and had no marker of HCV, HDV or HIV infection and no history of alcohol intake were enrolled. For each patient, liver HBV DNA and liver hsa-miR-125a-5p were quantified by real-time PCR in relation to ?-globin DNA or RNU6B, respectively. Liver fibrosis and necroinflammation were graded by applying Ishak's scoring system. Liver hsa-miR-125a-5p was detected in all patients enrolled and a correlation between its concentration and liver HBV DNA was demonstrated (p<0.0001). Higher liver hsa-miR-125a-5p concentrations were observed in patients with HBV-DNA plasma level >103 IU/ml (p<0.02), in those with HAI >6 (p?=?0.02) and those with fibrosis score >2 (p<0.02) than in patients with lower scores. Higher HBV-DNA liver concentrations were found in patients with abnormal AST (p?=?0.005) and ALT serum levels (p?=?0.05), in those with serum HBV DNA higher than 10E3 IU/mL (p?=?0.001) and those with fibrosis score >2 (p?=?0.02) than in patients with a lower load. By multivariate logistic regression analysis, liver hsa-miR-125a-5p was identified as an independent predictor of disease progression: O.R.?=?4.21, C.I. 95% ?=?1.08–16.43, p<0.05, for HAI >6; O.R.?=?3.12, C.I. 95% ?=?1.17–8.27, p<0.05, for fibrosis score >2. In conclusion, in HBsAg/anti-HBe-positive patients, the liver hsa-miR-125a-5p level correlated with liver and plasma HBV-DNA values and was associated to a more severe disease progression.

Coppola, Nicola; Potenza, Nicoletta; Pisaturo, Mariantonietta; Mosca, Nicola; Tonziello, Gilda; Signoriello, Giuseppe; Messina, Vincenzo; Sagnelli, Caterina; Russo, Aniello; Sagnelli, Evangelista

2013-01-01

99

Recent advances in the treatment of HIV/HBV and HIV/HCV co-infection.  

PubMed

Concurrent infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients positive for human immunodeficiency virus (HIV) is relatively common. The treatment of co-infected individuals is rather complex because the anti-viral therapy may be associated with drug-resistance, hepatotoxicity and lack of response. Herein, we present a summary of the available compounds and the recent recommendations concerning the therapeutic management of HIV/HBV and HIV/HCV co-infections. PMID:22530578

Masgala, A; Bonovas, S; Nikolopoulos, G K

2012-08-01

100

Prevalence of HBV and HCV dual infection in patients on haemodialysis.  

PubMed

Hepatitis viral infections are important causes of morbidity and mortality in haemodialysis patients. One hundred and thirty four patients attending haemodialysis unit were screened for the presence of HBV and HCV infections. Eight (5.9%) patients were HCV positive while two (1.4%) patients had HBV infection. A dual infection with both the viruses was observed in five patients (3.7%). PMID:15928421

Reddy, G A; Dakshinamurthy, K V; Neelaprasad, P; Gangadhar, T; Lakshmi, V

2005-01-01

101

Detection of primary YMDD mutations in HBV-related hepatocellular carcinoma using hybridization-fluorescence polarization.  

PubMed

Lamivudine is used for the treatment of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, HBV-related HCC patients with mutations in the tyrosine-methionine-aspartate-aspartate (YMDD) motif have no response to lamivudine therapy. The detection of YMDD mutations in HBV-related HCC patients may help guide the treatment of HCC. In this study, a simple, sensitive, reliable and cost-effective hybridization-fluorescence polarization assay for the detection of YMDD mutations in HCC was developed. A pair of general primers within the highly conserved region of the HBV polymerase gene was used in an asymmetric PCR. Three probes specific for the corresponding YMDD mutations labeled with different fluorescent reporters hybridized to their target amplicons, and hybridization was indicated by higher fluorescence polarization. The hybridization-fluorescence polarization assay was capable of detecting YMDD mutations at a limit of detection of 10 copies per reaction, and the assay was able to detect minor populations of viruses with primary YMDD mutations as low as 10%. The rates of primary YMDD mutations and the correlation between YMDD mutations and HBV genotypes in 251 HBV-related HCC patients were investigated using the hybridization-fluorescence polarization assay. PMID:23178585

Li, Ding; Cheng, Hong; Gong, Weidong; Jiang, Yinghao; Liang, Ping; Zhang, Ju

2013-02-01

102

Anti-HBV activities of Streblus asper and constituents of its roots.  

PubMed

The extracts from leaves, heartwood, barks and roots of the Streblus asper were investigated for anti-HBV activities, separately. The results suggested that the MeOH extracts of the heartwood, barks, and roots exhibited good anti-HBV activities. Further investigations displayed that ethyl acetate and n-butanol soluble parts of their MeOH extracts showed more significant anti-HBV activities. Moreover, a new lignan, together with 11 known compounds, was isolated from n-butanol-soluble part of MeOH extract of the roots of S. asper. The structures were elucidated by spectroscopic methods, including 1D NMR ((1)H NMR, (13)C NMR), 2D NMR (HMQC, HMBC) and HR-EI-MS experiments. Compounds 1-3 were evaluated for their anti-HBV activities. Honokiol showed significant anti-HBV activity with IC(50) values of 3.14?M and 4.74?M for HBsAg and HBeAg with no cytotoxicity respectively, while lamivudine (3TC, positive control) exhibited weak anti-HBV activity with IC(50) values of 11.81?M and 25.80?M for HBsAg and HBeAg respectively. PMID:22305944

Chen, Hong; Li, Jun; Wu, Qiang; Niu, Xiao-Tao; Tang, Mao-Tong; Guan, Xin-Lan; Li, Jian; Yang, Rui-Yun; Deng, Sheng-Ping; Su, Xiao-Jian

2012-06-01

103

Emergence of and takeover by hepatitis B virus (HBV) with rearrangements in the pre-S/S and pre-C/C genes during chronic HBV infection.  

PubMed Central

We have shown, by analyzing serial serum samples from a chronic hepatitis B virus (HBV) carrier, the emergence of HBV DNA molecules with nucleotide rearrangements in the pre-S/S and pre-C/C genes. Serum samples were obtained at four different times (1983, 1985, 1988, and 1989) from an HBsAg- and HBeAg-positive carrier with chronic hepatitis. The polymerase chain reaction was used to amplify the pre-S/S and pre-C/C genes. The amplified products were cloned, and 8 to 10 independent clones were sequenced. In 1983 and 1985 only one type of HBV DNA molecule was observed. Nucleotide divergence relative to the adw2 subtype was 4.7, 7.2, and 1.6%, for the pre-S1, pre-S2, and S regions, respectively, and 2.2 and 3.9% for the pre-C and C regions, respectively. In 1988 and 1989, HBV DNA forms with marked rearrangements of both the pre-S/S and pre-C/C regions were evidenced. In the pre-S/S region, they comprised two distinct HBV DNA molecules. The first showed nucleotide divergence of 20.4, 14.8, and 3.3% for the pre-S1, pre-S2, and S regions when compared with the adw2 sequence. In addition, nucleotide deletions in the pre-S1 region led to the appearance of a stop codon. The second was created by recombination between the original and mutated HBV DNA. In the pre-C/C region, the mutated viral DNA showed 11.7% divergence when compared with the adw2 sequence. A point mutation led to the creation of a stop codon in the pre-C region, together with an insertion of 36 nucleic acids in the core gene. Most of this DNA insertion was identical to that reported in an independent HBV isolate but showed no significant homology with known sequences. Semiquantitative estimation of the proportion of wild-type and mutated HBV DNA molecules showed a marked increase in the mutated forms during the period of follow-up. Sucrose gradient analysis indicated that the defective HBV DNA molecules were present in circulating virions. Western immunoblot analysis showed the appearance of modified translation products. Our findings thus indicate the emergence of and gradual takeover by mutated HBV DNA forms during the HBV chronic carrier state. The rearrangements we observed in the pre-S/S and pre-C/C genes might lead to changes in the immunogenicity of the viral particles and thus affect the clearance of the virus by the immune system. Images

Tran, A; Kremsdorf, D; Capel, F; Housset, C; Dauguet, C; Petit, M A; Brechot, C

1991-01-01

104

Geographical and Ethnic Distribution of the HBV C/D Recombinant on the Qinghai-Tibet Plateau  

PubMed Central

Two forms of hepatitis B virus (HBV) C/D recombinant have been identified in western China, but little is known about their geographical and ethnic distributions, and particularly the clinical significance and specific mutations in the pre-core region. To address these questions, a total of 624 chronic HBV carriers from four ethnic populations representing five provinces in western China were enrolled in this study. Genotypes were firstly determined by restriction fragment length polymorphism, and then confirmed by full or partial genome nucleotide sequencing. The distribution of HBV genotypes was as follows: HBV/B: 40 (6.4%); HBV/C: 221 (35.4%); HBV/D: 39 (6.3%); HBV/CD: 324 (51.9%). In the 324 HBV C/D recombinant infections, 244 (75.3%) were infected with the “CD1” and 80 (24.7%) were infected with the “CD2.” The distribution of HBV genotypes exhibited distinct patterns in different regions and ethnic populations. Geographically, the C/D recombinant was the most prevalent HBV strain on the Qinghai-Tibet Plateau. Ethnically, the C/D recombinant had a higher prevalence in Tibetan patients than in other populations. Clinically, patients with HBV/CD1 showed significantly lower levels of serum total bilirubin than patients with HBV/C2. The prevalence of HBeAg was comparable between patients with HBV/CD1 and HBV/C2 (63.3% vs 50.0%, P?=?0.118) whether patients were taken together or stratified by age into three groups (65.6% vs 58.8% in <30 years, P?=?0.758; 61.9% vs 48.0% in 30–50 years, P?=?0.244; 64.3% vs 33.3%, P?=?0.336). Virologically HBV/CD1 had a significantly lower frequency of G1896A than HBV/C2. In conclusion, the HBV C/D recombinant is restricted to the Qinghai-Tibet Plateau in western China and is found predominantly in Tibetans. The predominance of the premature pre-core stop mutation G1896A in patients with the HBV C/D recombinant may account for the higher prevalence of HBeAg in these patients.

Wang, Zhanhui; Chang, Ellen T.; Chen, Jinjun; Hou, Jinlin

2011-01-01

105

Conformational preferences of X-Pro sequences: Ala-Pro and Aib-Pro motifs.  

PubMed

Conformational preferences and prolyl cis-trans isomerizations of the X-Pro motifs (Ac-X-Pro-NHMe, X = Ala and Aib) are explored using the meta-hybrid functional M06-2X and the double-hybrid functional B2PLYP-D with empirical dispersion corrections in the gas phase and in water, where solvation free energies were calculated using the implicit SMD model. Ac-Ala-Pro-NHMe favors the type VI ?-turns in the gas phase and the open conformations in water. The populations of type VI ?-turns decrease from 71% in the gas phase to 21% in water, which is reasonably consistent with IR and NMR experimental results on tBoc-Ala-Pro-NHMe. However, Ac-Aib-Pro-NHMe prefers the type I ?-turns with ?-helical structures for both residues in the gas phase and in water, whose populations are estimated to be 66% in both phases. These calculated results may rationalize why most of the peptaibiotics containing the Aib-Pro sequence have a regular ?-helical conformation at the N- or C-terminus but a kinked ?-helical structure in the middle of the helix. The cis-trans isomerizations of the Ala-Pro and Aib-Pro peptide bonds proceed via the clockwise rotation with the different backbone conformations. The rotational barriers to cis-to-trans isomerization are estimated to be 19.73 kcal/mol for the Ala-Pro tripeptide and 16.64 kcal/mol for the Aib-Pro tripeptide in water, which indicates that the rotational barrier becomes lower by ~3 kcal/mol for the Aib-Pro peptide bond. The calculated rotational barrier for Ac-Ala-Pro-NHMe is consistent with the observed value of 19.3 kcal/mol for Suc-Ala-Ala-Pro-Phe-pNA from NMR experiments in a buffered solution. PMID:20949964

Byun, Byung Jin; Song, Il Keun; Chung, Yong Je; Ryu, Keun Ho; Kang, Young Kee

2010-11-11

106

Pharmacokinetics of Anti-HBV Polyoxometalate in Rats  

PubMed Central

Polyoxometalates are non-nucleoside analogs that have been proven to exhibit broad-spectrum antiviral activity. In particular, Cs2K4Na[SiW9Nb3O40].H2O 1 shows low toxicity and high activity against HBV. The preclinical pharmacokinetics of Compound 1 in rats were characterized by establishing and applying inductively coupled plasma-mass spectrometry method to determine the concentration of W in plasma, urine, feces, bile and organ samples. The quantitative ICP-MS method demonstrated good sensitivity and application in the pharmacokinetics study of polyoxometalates. The pharmacokinetic behavior of Compound 1 after intravenous or oral administration fit a two-compartment model. Tmax ranges from 0.1 h to 3 h and the T1/2 of Compound 1 is between 20 h and 30 h. The absolute bioavailability of Compound 1 at 45, 180 and 720 mg/kg groups were 23.68%, 14.67% and 11.93%, respectively. The rates of plasma protein binding of Compound 1 at 9, 18 and 36 mg/ml of Compound 1 are 62.13±9.41%, 71.20±24.98% and 49.00±25.59%, respectively. Compound 1 was widely distributed throughout the body, and high levels of compound 1 were found in the kidney and liver. The level of Compound 1 in excretion was lower: 30% for urine, 0.28% for feces and 0.42% for bile, respectively. For elaborate pharmacokinetic characteristics to be fully understood, the metabolism of Compound 1 needs to be studied further.

Qi, Yanfei; Li, Jinhua; Song, Xiuling; Li, Li; Yin, Dehui; Xu, Kun; Li, Juan

2014-01-01

107

The inverse association of serum HBV DNA level with HDL and adiponectin in chronic hepatitis B infection  

PubMed Central

BACKGROUND The natural history of hepatitis B virus (HBV) is complex and influenced by the level of viral replication and host factors. The hepatoprotective role of high density lipoproteins (HDL) and adiponectin as host factors on HBV persistence is less well understood. METHODS To investigate correlation between HBV DNA level with clinical parameters in patients with chronic hepatitis B, 92 male subjects with HBV infection without any risk factors for diabetes were enrolled in this study. Age and BMI of the study population were matched and HBV DNA, ALT, tumor necrosis factor alpha (TNF-?), adiponectin and lipid levels was measured. RESULTS Serum HBV DNA correlated inversely with serum HDL level (r = -0.23; P = 0.014). The median of log copies/ml for HBV DNA (3.67) was considered as cut off point. Patients with HBV DNA level higher than cut off point had lower adiponectin (8.7 ± 5.3 vs 10.7 ± 4.9 ?g/ml p = 0.05). Also, adiponectin had a negative correlation with TNF-? (r = -0.21, P = 0.04) and positive correlations with HDL (r = 0.18, P = 0.043).Multivariate regression models show that serum HDL level is an independed factor to predict serum HBV DNA. CONCLUSION Our findings showed that higher HBV DNA levels are associated with lower HDL and adiponectin but induced TNF-alpha values.

2010-01-01

108

Therapeutic recovery of hepatitis B virus (HBV)-induced hepatocyte-intrinsic immune defect reverses systemic adaptive immune tolerance.  

PubMed

Hepatitis B virus (HBV) persistence aggravates hepatic immunotolerance, leading to the failure of cell-intrinsic type I interferon and antiviral response, but whether and how HBV-induced hepatocyte-intrinsic tolerance influences systemic adaptive immunity has never been reported, which is becoming the major obstacle for chronic HBV therapy. In this study, an HBV-persistent mouse, established by hydrodynamic injection of an HBV-genome-containing plasmid, exhibited not only hepatocyte-intrinsic but also systemic immunotolerance to HBV rechallenge. HBV-specific CD8(+) T-cell and anti-HBs antibody generation were systemically impaired by HBV persistence in hepatocytes. Interestingly, HBV-induced hepatocyte-intrinsic immune tolerance was reversed when a dually functional vector containing both an immunostimulating single-stranded RNA (ssRNA) and an HBx-silencing short hairpin RNA (shRNA) was administered, and the systemic anti-HBV adaptive immune responses, including CD8(+) T-cell and anti-HBs antibody responses, were efficiently recovered. During this process, CD8(+) T cells and interferon-gamma (IFN-?) secreted play a critical role in clearance of HBV. However, when IFN-?/? receptor was blocked or the Toll-like receptor (TLR)7 signaling pathway was inhibited, the activation of CD8(+) T cells and clearance of HBV was significantly impaired. Conclusion: These results suggest that recovery of HBV-impaired hepatocyte-intrinsic innate immunity by the dually functional vector might overcome systemic adaptive immunotolerance in an IFN-?- and TLR7-dependent manner. The strategy holds promise for therapeutic intervention of chronic persistent virus infection and associated cancers. PMID:23447417

Lan, Peixiang; Zhang, Cai; Han, Qiuju; Zhang, Jian; Tian, Zhigang

2013-07-01

109

A336C\\/A336T\\/T337C variations in HBV core gene and spontaneous hepatitis B e antigen loss in chronic hepatitis B patients  

Microsoft Academic Search

Background  A336C\\/A336T\\/T337C variations in HBV core gene were demonstrated to relate to the decreases in serum HBV DNA levels and HBV\\u000a replication in chronic hepatitis B patients. Usually the drastic decrease in serum HBV DNA levels correlates with spontaneous\\u000a HBeAg loss during the course of chronic HBV infection. The aim of the present study was to investigate whether there was correlation

Wen Fan; Lu Huang; Zhiming zhou; Yirong Li

2011-01-01

110

Wild type and YMDD variant of hepatitis B virus: No difference in viral kinetics on lamivudine\\/tenofovir therapy in HIV–HBV co-infected patients  

Microsoft Academic Search

Prolonged lamivudine therapy has been identified as the major risk for the development of resistance in HBV, with rates of 90% after 4 years of treatment. Tenofovir disoproxil fumarate showed activity against both wild type and lamivudine resistant HBV in HIV–HBV co-infected patients. In order to compare the efficacy of lamivudine\\/tenofovir treatment we investigated detailed HBV kinetics in 13 HIV–HBV

T. E. M. S. de Vries-Sluijs; A. A. van der Eijk; B. E. Hansen; A. D. M. E. Osterhaus; R. A. de Man; M. E. van der Ende

2006-01-01

111

Long-Term Protection against HBV Chronic Carriage of Gambian Adolescents Vaccinated in Infancy and Immune Response in HBV Booster Trial in Adolescence  

PubMed Central

Background Chronic infection with hepatitis B virus (HBV) arising in childhood is associated with hepatocellular carcinoma in adult life. Between 1986 and 1990, approximately 120,000 Gambian newborns were enrolled in a randomised controlled trial to assess the effectiveness of infant HBV vaccination on the prevention of hepatocellular carcinoma in adulthood. These children are now in adolescence and approaching adulthood, when the onset of sexual activity may challenge their hepatitis B immunity. Thus a booster dose in adolescence could be important to maintain long-term protection. Methods Fifteen years after the start of the HBV infant vaccination study, 492 vaccinated and 424 unvaccinated children were identified to determine vaccine efficacy against infection and carriage in adolescence. At the same time, 297 of the 492 infant-vaccinated subjects were randomly offered a booster dose of HBV vaccine. Anti-HBs was measured before the booster, and two weeks and 1 year afterwards (ISRCTN71271385). Results Vaccine efficacy 15 years after vaccination was 67.0% against infection as manifest by anti-HBc positivity (95% CI 58.2–74.6%), and 96.6% against HBsAg carriage (95% CI 91.5–100%). 31.2% of participants had detectable anti-HBs with a GMC of 32 IU/l. For 168 boosted participants GMC anti-HBs responses were 38 IU/l prior to vaccination, 524 IU/l two weeks after boosting, and 101 IU/l after 1 year. Conclusions HBV vaccination in infants confers very good protection against carriage up to 15 years of age, although a large proportion of vaccinated subjects did not have detectable anti-HBs at this age. The response to boosting persisted for at least a year. Trial Registration Controlled-Trials.com ISRCTN71271385

van der Sande, Marianne A.B.; Waight, Pauline A.; Mendy, Maimuna; Zaman, Syed; Kaye, Steve; Sam, Omar; Kahn, Abi; Jeffries, David; Akum, Aveika A.; Hall, Andrew J.; Bah, Ebrima; McConkey, Samuel J.; Hainaut, Pierre; Whittle, Hilton C.

2007-01-01

112

HLA-DQ polymorphisms with HBV infection: different outcomes upon infection and prognosis to lamivudine therapy.  

PubMed

Two recent genome-wide studies showed that the single-nucleotide polymorphisms in the HLA-DQ region (rs2856718 and rs9275572) were associated with chronic hepatitis B virus infection and chronic hepatitis C virus-associated hepatocellular carcinoma in Japanese patients. We tested the effects of the two single-nucleotide polymorphisms for all major HBV outcomes and lamivudine treatment in Han Chinese. A total of 1649 samples were enrolled, and peripheral blood samples were collected in this study. The single-nucleotide polymorphisms in the HLA-DQ region were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Our study demonstrated the clear relevance of HLA-DQ rs2856718 and rs9275572 with HBV susceptibility, natural clearance and HBV-associated HCC. HLA-DQ rs2856718G and rs9275572A were strongly associated with decreased risk of chronic HBV infection (odds ratio = 0.641; P = 2.64 × 10(-4) ; odds ratio = 0.627, P = 7.22 × 10(-5) ) and HBV natural clearance (odds ratio = 0.610; P = 4.80 × 10(-4) ; odds ratio = 0.714, P = 0.013). Moreover, rs9275572A was also associated with development of cirrhosis and hepatocellular carcinoma (odds ratio = 0.632, P = 0.008). In addition, we showed for the first time to our knowledge that rs9275572 was a predictor for lamivudine therapy (viral response: odds ratio = 2.599, P = 4.43 × 10(-4) ; biochemical response: odds ratio = 2.279, P = 4.23 × 10(-4) ). Our study suggested that HLA-DQ loci were associated with both HBV clearance and HBV-related diseases and outcomes of lamivudine treatment in Han Chinese. PMID:24750255

Zhang, X; Jia, J; Dong, J; Yu, F; Ma, N; Li, M; Liu, X; Liu, W; Li, T; Liu, D

2014-07-01

113

Exan™ Pro: Process visualization tool  

Microsoft Academic Search

Exan Pro is a powerful tool for the visualization of process modeling results, which can be obtained using Aspen Plus™ or other flowsheeting packages. Clear Exergy, Energy, Molar, Mass, Volume, Process and Block flow diagrams can be created in an automatic way. In a flow diagram, the width of a stream schematically represents its contents. Exan Pro especially allows you

A. J. G. G. Graveland

1999-01-01

114

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

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 infection with good immune response 28%. Women who were anti-HBe positive were a low-risk group, and their babies were most likely to remain free of HBV infection (occult or overt) and had good immune response to the vaccine. Maternal HBeAg-positive status and negativity for anti-HBe predicted not only overt but also any infection (both overt and occult) in babies. In addition, high maternal HBV DNA and treatment with vaccine alone were significant factors for overt HBV infection in babies. The current practice of administration of vaccine with HBIG at birth to babies born of HBsAg-positive mothers is not effective in preventing occult HBV infection in babies, which may be up to 40%. Because the most important risk factors for mother-to-baby transmission of HBV infection are the replicative status and high HBV DNA level in mothers; it will be worthwhile investigating the role of antivirals and HBIG administration during pregnancy to prevent mother-to-child transmission of HBV infection. PMID:24168259

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

115

Polyarteritis nodosa and extrahepatic manifestations of HBV infection: the case against autoimmune intervention in pathogenesis.  

PubMed

Numerous extrahepatic manifestations have been reported in patients with both acute and chronic hepatitis B (arthralgias or arthritis, skin rashes, glomerulonephritis and neuritis), all of which are present in polyarteritis nodosa (PAN) which is the most unique and spectacular extrahepatic manifestation. In the 1970s, the frequency of PAN due to the hepatitis B (HBV) reached 30%. Immunization programs explain the decrease and it is now down to 7%. PAN usually occurs within 6 months of infection. Clinical manifestations reflect this most classic form of PAN, Hepatic manifestations including, ALT/AST elevations are mild and usually overlooked. Besides HBV, other viruses may be responsible for cases of vasculitides including PAN, HIV, Parvovirus B19, and EBV. Different pathogenic mechanisms have been identified but immune complexes are mainly thought to be responsible. In glomerulonephritis, detailed immunostaining and ultrastructural findings indicate that HBe antigen (Ag) is more likely to be the responsible antigen. In PAN, fewer reports are available and early studies with poorly defined antibodies need to be revisited. Interestingly almost all cases of HBV/PAN are associated with wild-type HBV infection, characterised by HBe antigenemia and high HBV replication, supporting the concept that lesions could result from the deposit of viral Ag/Ab complexes soluble in Ag excess, possibly involving HBe Ag. The recent observation of PAN cases associated with precore mutation which abrogates the formation of HBe Ag challenges this view. It may suggest that other, still undefined, circulating HBV-related Ag(s) distinct from HBe Ag could be involved. Remarkably, none of the HBV/PAN cases or glomerulonephritis exhibit antineutrophil cycoplasmic antibodies (ANCA) reactivity. Viral PAN can now be completely separated from other form of vasculitis mostly autoimmune in nature. Based on the efficacy of antiviral agents in chronic hepatitis B and of plasma exchanges in PAN we combined both therapies to treat HBV PAN. This was associated with swift recovery, even in the most severe forms. The perfect time correlation between inhibition of virus replication and resolution of all bioclinical signs suggest a direct pathogenic role of the virus possibly via immune complexes. Traditional immunosuppressive and steroid therapy should no longer be used for HBV PAN cases. PMID:11334492

Trepo, C; Guillevin, L

2001-05-01

116

Modulation of the antioxidant/pro-oxidant balance, cytotoxicity and antiviral actions of grape seed extracts.  

PubMed

Grape seed extracts (GSEs) were investigated in yeast cells harbouring defects in their antioxidant system (regarding the cellular growth and growth recovery from H2O2 insult). GSEs antioxidant activity was detected in wild-type and mutant strains ?cta1, ?gsh1 and ?oye2glr1, while pro-oxidant activity in ?sod1 cells was seen. Assessment of proliferation of prostate cancer PC3 and HBV-replicating HepG2 2.2.15 cells treated with GSEs has shown higher cytotoxicity of red grape seed extract (RW) than white grape seed extract (WW) subjective to dose and period of administration. No antiviral effect was detected by measuring the secreted virion particles in HepG2 2.2.15 cells treated with GSEs. The GSEs play a dual antioxidant/pro-oxidant role in vivo according with the cellular antioxidant system deficiencies and exhibit cytotoxic properties in PC3 and HepG2 2.2.15 cell lines, but no antiviral action against HBV. PMID:23993573

Ignea, Codru?a; Doroban?u, Cristina Mihaela; Mintoff, Christopher Paul; Branza-Nichita, Norica; Ladomery, Michael R; Kefalas, Panagiotis; Chedea, Veronica Sanda

2013-12-15

117

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

PubMed

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

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

118

Role of Single Nucleotide Polymorphisms of KIF1B Gene in HBV-Associated Viral Hepatitis  

PubMed Central

Background/Aim Kinesin family member 1B (KIF1B) gene resides in the chromosomal region 1p36.22 and has been reported to have frequent deletions in a variety of human cancers. A recent genome wide association study (GWAS) study conducted on a Chinese population has reported the involvement of a KIF1B genetic variant in Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aims to investigate the significance of KIF1B genetic variations in HBV-associated hepatitis in patients of Saudi Arabian ethnicity. Methods TaqMan genotyping assay was used to investigate the association of three SNPs (rs17401966, rs12734551, and rs3748578) in 584 normal healthy controls and 660 HBV-infected patients. The patients were categorized into inactive carriers (Case I), active carriers (Case II), Cirrhosis (Case III) and Cirrhosis-HCC (Case IV) sub-groups. Results Since SNPs rs12734551 and rs3748578 are in strong linkage disequilibrium (LD) with rs17401966, only results for the latter SNP are reported. Therefore, the allele frequency of rs17401966 among HBV-infected patients and healthy controls were comparable and therefore, no significant association was observed (P?=?0.2811, Odds Ratio (OR) 0.897). A similar analysis was performed among the different sub-groups in order to determine whether KIF1B SNPs were associated with the advancement of the disease. No significant differences were observed in any of the comparisons performed. Conclusion Polymorphisms at KIF1B gene locus investigated in this study showed no significant association with HBV infection or with HBV-associated diseases such as liver cirrhosis or HCC.

Al-Qahtani, Ahmed; Al-Anazi, Mashael; Viswan, Nisha A.; Khalaf, Nisreen; Abdo, Ayman A.; Sanai, Faisal M.; Al-Ashgar, Hamad; Al-Ahdal, Mohammed

2012-01-01

119

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

PubMed

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

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

2014-01-01

120

HBV Induced HCC: Major Risk Factors from Genetic to Molecular Level  

PubMed Central

Hepatocellular carcinoma (HCC) is a deadly and emerging disease leading to death in Asian countries. High hepatitis B virus (HBV) load and chronic hepatitis B (CHB) infection increase the risk of developing HCC. HBV is a DNA virus that can integrate DNA into host genome thereby increase the yield of transactivator protein HBxAg that may deregulate many pathways involving in metabolism of cells. Several monogenic and polygenic risk factors are also involved in HCC development. This review summarizes the mechanism involved in HCC development and discusses some promising therapies to make HCC curative.

Ayub, Ambreen; Ashfaq, Usman Ali; Haque, Asma

2013-01-01

121

Decreased Prohepcidin Levels in Patients with HBV-Related Liver Disease: Relation with Ferritin Levels  

Microsoft Academic Search

Background  Levels of prohepcidin, a homeostatic regulator of iron absorption, are altered in chronic hepatitis C and liver cirrhosis.\\u000a However, data on the potential alterations of prohepcidin in patients with HBV-related liver disease are scarce. We investigated\\u000a whether serum prohepcidin is related to iron overload and perenchymal dysfuction in HBV-related liver disease.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Three groups of subjects were studied: 66 patients with

Oya YonalFiliz; Filiz Akyuz; Kadir Demir; Sevgi Ciftci; Fahriye Keskin; Binnur Pinarbasi; Ahmet Uyanikoglu; Halim Issever; Sadakat Ozdil; Gungor Boztas; Fatih Besisik; Sabahattin Kaymakoglu; Yilmaz Cakaloglu; Zeynel Mungan; Atilla Okten

2010-01-01

122

Are isolated anti-HBc blood donors in high risk group? The detection of HBV DNA in isolated anti-HBc cases with nucleic acid amplification test (NAT) based on transcription-mediated amplification (TMA) and HBV discrimination  

Microsoft Academic Search

AimHepatitis B virus (HBV) can be transmitted by blood transfusions even so using serological tests having high sensitivity and specificity. We aimed to detect HBV DNA in isolated Anti-HBc donors and show if they have transfusion risk or not.

Hüsnü Altunay; Erdogan Kosan; Ilhan Birinci; Armagan Aksoy; Kaan Kirali; Suat Saribas; Mustafa Aslan; Pelin Yuksel; Esra Alan; Osman Sadi Yenen; Bekir Kocazeybek

2010-01-01

123

Evaluation of antibody frequency against HBV, HCV and HTLV-1  

PubMed Central

Aim This study was designed to evaluate the frequency of antibody against these viruses in individuals attending the endoscopy ward of Taleghani hospital Tehran, Iran. Background Blood-borne viruses such as hepatitis B and hepatitis C virus and HTLV-1 virus are among the world’s public health problems. Hepatitis viruses cause liver problems and HTLV-1 infection can lead to adult T-Cell lymphoma (ATL). Patients and methods Blood samples of 219 individuals attending the endoscopy ward of Taleghani hospital between years 2009-2011 were collected. A questionnaire containing demographic data was completed for each subject. Blood samples were tested for antibody against HTLV-1, HCV and HBc by ELISA (Dia.pro Italy). In case of positive results for anti-HBc, samples were also tested for HBs Ag antigen. Results Ninety two subjects were male and 127 were female. Mean age of the population was 39.87 ± 16.47. None of the subjects had anti-HCV antibody, while 4 of them had anti-HTLV-1 antibody and 26 anti-HBc antibody; which only two of these individuals had HBs Antibody. Conclusion The results of this study show that frequency of anti-HCV and anti-HTLV-1 antibodies are very low, while the frequency of anti-HBc was higher in the population. Since HTLV-1 is the causative agent of a type of blood cancer, it seems that screening of donated bloods in this region should be considered.

Tahaei, Seyed Mohammad Ebrahim; Fatemi, Seyed Reza; Azimzadeh, Pedram; Mirsattari, Dariush; Sanati, Azar; Sharifian, Afsaneh

2012-01-01

124

Functional interplay between hepatitis B virus X protein and human miR-125a in HBV infection.  

PubMed

The hepatitis B virus (HBV) is a widespread human pathogen and chronic HBV infection is a major risk factor for hepatocellular carcinoma (HCC). Some cellular microRNAs are emerging as important regulators of virus-host interaction, indirectly or directly modulating HBV replication and pathogenesis. miR-125a binds the viral transcript encoding the surface antigen and interferes with its expression, thus inhibiting viral replication. Intriguingly, liver miR-125a expression has been found increased in patients with high levels of hepatic HBV-DNA. The present study investigates the mechanism by which liver exposure to HBV induces the expression of miR-125a. The analyses were first performed on liver biopsies from HBV patients, showing that the expression of the viral transactivator X protein (HBx) paralleled the increase of miR-125a expression. Then, transfection of HCC cell lines with an HBx-expressing vector showed a substantial increase of miR-125a expression. Overall, the available data depict a self-inhibitory feedback loop in which HBV, through HBx, increases the expression of miR-125a, that in turn interferes with expression of HBV surface antigen, thus repressing viral replication. PMID:24824183

Mosca, Nicola; Castiello, Filomena; Coppola, Nicola; Trotta, Maria Consiglia; Sagnelli, Caterina; Pisaturo, Mariantonietta; Sagnelli, Evangelista; Russo, Aniello; Potenza, Nicoletta

2014-06-20

125

MHC Class I Presented T Cell Epitopes as Potential Antigens for Therapeutic Vaccine against HBV Chronic Infection  

PubMed Central

Approximately 370 million people worldwide are chronically infected with hepatitis B virus (HBV). Despite the success of the prophylactic HBV vaccine, no therapeutic vaccine or other immunotherapy modality is available for treatment of chronically infected individuals. Clearance of HBV depends on robust, sustained CD8+ T activity; however, the limited numbers of therapeutic vaccines tested have not induced such a response. Most of these vaccines have relied on peptide prediction algorithms to identify MHC-I epitopes or characterization of T cell responses during acute infection. Here, we took an immunoproteomic approach to characterize MHC-I restricted epitopes from cells chronically infected with HBV and therefore more likely to represent the true targets of CD8+ T cells during chronic infection. In this study, we identified eight novel MHC-I restricted epitopes derived from a broad range of HBV proteins that were capable of activating CD8+ T cells. Furthermore, five of the eight epitopes were able to bind HLA-A2 and A24 alleles and activated HBV specific T cell responses. These epitopes also have potential as new tools to characterize T cell immunity in chronic HBV infection and may serve as candidate antigens for a therapeutic vaccine against HBV infection.

Comber, Joseph D.; Shetty, Vivekananda; Testa, James S.

2014-01-01

126

How Can We Make Decision for Patients With Chronic Hepatitis B According to Hepatitis B Virus (HBV) DNA Level?  

PubMed Central

Background: HBeAg negative hepatitis B infection exerts both inactive carrier state and chronic active hepatitis, which are sometimes difficult to differentiate. Serial hepatitis B virus (HBV) DNA quantification, alanine transaminase (ALT) measurement, and liver histology assessment can help to differentiate these forms of hepatitis B infection. Objectives: We aimed to clarify the clinical and laboratory characteristics of HBeAg negative hepatitis B patients. Patients and Methods: Patients with hepatitis B, referred to Tehran Blood Transfusion Hepatitis Clinic from 2011 to 2013, were included and followed for one year. Laboratory assessments including liver function tests, HBV DNA quantification, and liver biopsy (for some cases) were performed. Results: Two hundred forty-three HBeAg negative hepatitis B patients were stratified into three groups based on to their HBV DNA level including group 1 (G1) with HBV DNA level < 2000 IU/mL, group 2 (G2) with HBV DNA level 2000-20000 IU/mL, and group 3 (G3) with HBV DNA level > 20000 IU/mL. The G2 had more similarity to G1 than G3 regarding their clinical characteristics. Conclusions: It is concluded that most HBeAg negative hepatitis B patients with serum HBV DNA level of 2000-20000 IU/mL, persistent normal ALT concentration, and no or mild liver damage on biopsy can be clinically managed as HBV inactive carriers.

Keshvari, Maryam; Alavian, Seyed Moayed; Sharafi, Heidar

2014-01-01

127

HBV promotes the proliferation of hepatic stellate cells via the PDGF-B/PDGFR-? signaling pathway in vitro.  

PubMed

The activation of hepatic stellate cells (HSCs) is closely associated with liver fibrosis in chronic hepatitis B virus (HBV) infection. However, the molecular mechanisms leading to HSC activation remain unclear. It has been reported that the platelet-derived growth factor-B (PDGF-B)/PDGF receptor-? (PDGFR-?) signaling pathway is involved in this process. Thus, we investigated whether HBV and its protein contribute to HSC proliferation by the PDGF-B/PDGFR-? signaling pathway. HBV particles were purified from the supernatant of HepG2.2.15 cells by ultracentrifugation and the cell lines carrying HBV preS, e, c or x genes were obtained. After incubation with HBV particles or co-cultured with the cell lines expressed in the viral protein, the proliferation of LX-2 cells, an HSC cell line, were detected by flow cyto-metry and real-time PCR and the expression of molecules related to the PDGF-B/PDGFR-? signaling pathway were further measured. Our results indicated that HBV particles, c and x proteins promoted LX-2 proliferation and increased the mRNA levels of PDGF-B, PDGFR-?, collagen-I and ?-smooth muscle actin (?-SMA), as well as the phosphorylation of PDGFR-?; however, the expression protein levels of PDGF-B and PDGFR-? remained unchanged. In conclusion, HBV particles and HBV c and x proteins promote HSC proliferation and fibrogenesis in vitro and the PDGF-B/PDGFR-? signaling pathway is important in this process. PMID:23042547

Bai, Qixuan; An, Jing; Wu, Xiaoning; You, Hong; Ma, Hong; Liu, Tianhui; Gao, Na; Jia, Jidong

2012-12-01

128

Improved rolling circle amplification (RCA) of hepatitis B virus (HBV) relaxed-circular serum DNA (RC-DNA).  

PubMed

For functional analysis of HBV isolates, epidemiological studies and correct identification of recombinant genomes, the amplification of complete genomes is necessary. A method for completely in vitro amplification of full-length HBV genomes starting from serum RC-DNA is described. This uses in vitro completion/ligation of plus-strand HBV RC-DNA and amplification using Rolling-Circle Amplification, eventually followed by a genomic PCR. The method can amplify complete HBV genomes from sera with viral loads ranging from >1.0E+8 IU/ml down to 1.0E+3 IU/ml. The method can be applied to archived sera that have undergone long-term storage or to archived DNA serum extracts. The genomes can easily be cloned. HBV genotypes A-G can all be amplified with no apparent problems. A recombinant subgenotype A3/genotype E genome was identified and fully sequenced. PMID:23928222

Martel, Nora; Gomes, Selma A; Chemin, Isabelle; Trépo, Christian; Kay, Alan

2013-11-01

129

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

MedlinePLUS

... normal. By the time symptoms such as abdominal pain or jaundice (dark urine and yellow discoloration of the skin or eyes) appear, it is often too late for treatment to be effective. 1. A mother-to-child infection For Asians, HBV is commonly transmitted from ...

130

Characterization of Hepatitis B virus (HBV) genotypes in patients from Rond?nia, Brazil  

PubMed Central

Background Hepatitis B virus (HBV) can be classified into nine genotypes (A-I) defined by sequence divergence of more than 8% based on the complete genome. This study aims to identify the genotypic distribution of HBV in 40 HBsAg-positive patients from Rondônia, Brazil. A fragment of 1306 bp partially comprising surface and polymerase overlapping genes was amplified by PCR. Amplified DNA was purified and sequenced. Amplified DNA was purified and sequenced on an ABI PRISM® 377 Automatic Sequencer (Applied Biosystems, Foster City, CA, USA). The obtained sequences were aligned with reference sequences obtained from the GenBank using Clustal X software and then edited with Se-Al software. Phylogenetic analyses were conducted by the Markov Chain Monte Carlo (MCMC) approach using BEAST v.1.5.3. Results The subgenotypes distribution was A1 (37.1%), D3 (22.8%), F2a (20.0%), D4 (17.1%) and D2 (2.8%). Conclusions These results for the first HBV genotypic characterization in Rondônia state are consistent with other studies in Brazil, showing the presence of several HBV genotypes that reflects the mixed origin of the population, involving descendants from Native Americans, Europeans, and Africans.

2010-01-01

131

Hepatitis B virus-transfected Hep G2 cells demonstrate genetic alterations and de novo viral integration in cells replicating HBV  

Microsoft Academic Search

Hepatitis B virus (HBV) is a major etiological factor associated with hepatocarcinogenesis, but its role in the transformation process remains unclear. We previously documented the accumulation of genetic alterations in a HBV-transfected cell line. In the present study, we addressed the effect of HBV and its replication on the genome and phenotype of the host cell. Parental HBV-free Hep G2

Kristin W Livezey; Dmitri Negorev; Daniela Simon

2000-01-01

132

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

Microsoft Academic Search

Background and aim  Transmission of hepatitis B virus (HBV) infection occurs in up to 87.5% of HBsAg-negative recipients of anti-HBc-positive\\u000a donor livers in the absence of HBV prophylaxis. There is no standardized prophylactic regimen to prevent HBV infection in\\u000a this setting. The aim of this study was to determine the long-term efficacy of nucleoside analogue to prevent HBV infection\\u000a in this

Watcharasak Chotiyaputta; Shawn J. Pelletier; Robert J. Fontana; Anna S. F. Lok

2010-01-01

133

In vitro characterisation of the anti-hepatitis B virus (HBV) activity and cross-resistance profile of 2', 3'-dideoxy-3'-fluoroguanosine  

Microsoft Academic Search

The fluorinated guanosine analog 2,3-dideoxy-3-fluoroguanosine (FLG) was shown to inhibit wild-type (wt) hepatitis B virus (HBV) replication in a human hepatoma cell line permanently expressing HBV. Experiments performed in the duck model of HBV infection also showed its in vivo antiviral activity. In this study, we investigated the mechanism of inhibition of FLG on HBV replication and its profile of

A. C. Jacquard; M. N. Brunelle; C. Pichoud; D. Durantel; S. Carrouée-Durantel; C. Trepo; F. Zoulim

134

Non-radioactive hepatitis B virus DNA probe for detection of HBV-DNA in serum.  

PubMed

A diagnostic test has been developed to detect hepatitis B virus (HBV) DNA in human sera. This test involves a dot-blot technique in which non-radioactive nucleic acid labelled with 2-acetylaminofluorene (AAF) is used as probe. Two series of human sera from 228 blood donors and 113 HBsAg chronic carriers were tested by hybridization with the same DNA probe labelled either with AAF or with 32P. A correlation between the techniques was observed for 328 sera (96%), and using the non-radioactive test it was possible to detect 56 (86%) of the 65 HBV-DNA-positive patients. A comparative study of the HBeAg/anti-HBe status and the presence of HBV-DNA was carried out on the sera from 113 HBsAg chronic carriers, 65 of which were positive for HBeAg and 29 of which were positive for anti-HBe antibodies. With the AAF test, 44 of the HBeAg-positive sera were positive, while 5 of the anti-HBe-positive sera were positive. This study shows that, although this non-radioactive test is slightly less sensitive than the radioactive hybridization assay (RHA), it can be used for a survey of HBV carriers. Dissociation of the viral multiplication and the HBe/anti-HBe status was identified with the AAF test as well as with the RHA. It would therefore appear that the AAF test described here may be used for the extensive survey of HBV multiplication. PMID:3320180

Larzul, D; Thiers, V; Courouce, A M; Bréchot, C; Guesdon, J L

1987-10-01

135

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

SciTech Connect

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.

Wang, Wei; Liu, Yang; Zu, Xiangyang; Jin, Rui [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China)] [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China); Xiao, Gengfu, E-mail: xiaogf@wh.iov.cn [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China)] [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China)

2011-09-09

136

HBV genotype C strains with spontaneous YMDD mutations may be a risk factor for hepatocellular carcinoma.  

PubMed

HBV has a relatively high mutation rate in its genome and most of these mutations are associated with the curative effect of nucleoside analogs. In this study, 1,424 patients with HBV-related liver diseases not treated with antiviral drugs, including 197 asymptomatic HBV carriers, 769 chronic hepatitis B patients, 145 acute-on-chronic liver failure (ACLF) patients, 187 HBV-related liver cirrhosis patients, and 126 HBV-related HCC patients, were selected to investigate the distribution and clinical significance of spontaneous YMDD mutations in liver diseases at different stages. Spontaneous YMDD mutations were detected in all stages of liver diseases and the YIDD variant was the dominant mutation type. The mutation rate was higher in genotype C strains than in genotype B strains. The ?(2) subdivision method showed that the spontaneous YMDD mutation rate in HCC was higher than that in other liver diseases. The difference in spontaneous YMDD mutation rates in patients with liver diseases infected with genotype C strains at different stages was statistically significant. Spontaneous YMDD mutation rates in patients with liver diseases infected with genotype C strains at different stages were then compared one to one using the ?(2) subdivision method. The results showed that the spontaneous YMDD mutation rate in HCC was higher than that in other liver diseases. Taken together, these results indicated that spontaneous YMDD mutations are more likely to occur in patients infected with genotype C strains, and genotype C strains with spontaneous YMDD mutations may be a risk factor for HCC. J. Med. Virol. 86:913-917, 2014. © 2017 Wiley Periodicals, Inc. PMID:24615989

Yang, Jiahong; Chen, Xuebing; Zhang, Hao; Chen, Gao

2014-06-01

137

HCV, HBV, and HIV seroprevalence, coinfections, and related behaviors among male injection drug users in Arak, Iran.  

PubMed

This study explored the prevalence and related risk behaviors for hepatitis C (HCV), hepatitis B (HBV), and human immunodeficiency virus (HIV) among a sample of male injection drug users (IDUs) in Arak, Iran. One hundred male IDUs attending methadone maintenance clinics between April and September 2012 were enrolled and evaluated for HCV, HBV, and HIV infection. The majority of study participants (56%) had evidence of HCV exposure, 6% had evidence of HBV, and 19% were HIV-infected. Coinfections were frequent; 15% had evidence of HIV and HCV, 6% had evidence of HBV and HCV, and 5% had serologic markers for all three infections. Most (84%) were susceptible to HBV infection. A history of any syringe sharing (54%) and syringe sharing in prison (25%) were common. In bivariate analyses, a history of any syringe sharing and syringe sharing in prison were both associated with all three viral infections. The high prevalence of HCV, HBV, HIV, and coinfections among IDU in Arak is concerning and indicates rapid disease spread outside of Iran's main urban centers. Prevention efforts should expand vaccination for IDUs who are nonimmune to HBV and continue to target syringe sharing with efforts such as needle exchange programs, including inside prisons. PMID:24499303

Ramezani, Amitis; Amirmoezi, Reihaneh; Volk, Jonathan E; Aghakhani, Arezoo; Zarinfar, Nader; McFarland, Willi; Banifazl, Mohammad; Mostafavi, Ehsan; Eslamifar, Ali; Sofian, Masoomeh

2014-09-01

138

Impact of hepatitis B virus genotypes and surface antigen variants on the performance of HBV real time PCR quantification.  

PubMed

Quantitative PCR assays used to monitor hepatitis B virus (HBV) load differ in their ability to detect different HBV variants. This study evaluated the performance of the Abbott RT PCR assay for quantitating DNA from different HBV genotypes and from HBV variants bearing HBsAg gene mutations. The study was performed on a randomly-selected sample with a viral load >6logIU/mL for each genotype and on 25 HBsAg variants. Each sample was assayed using the Abbott RT assay and with the Roche Cobas AmpliPrep-Cobas TaqMan as a reference method. All HBV genotypes were detected with the Abbott RT assay with an equivalent dynamic range (1-8logIU/mL). For each genotype, the data suggest that the assay was linear over the entire dilution range (r(2): 0.985-0.995). For the 25 HBsAg variants, viral titres determined with the two assays correlated well (r(2): 0.929). The mean difference between the two methods was -0.295 (95% CI: -0.520 to -0.071). The difference was lower than 1log unit in all but two cases. In conclusion, the Abbott RT assay can detect and quantify DNA from different HBV variants with equivalent performance and is thus suitable for routine monitoring of patients with chronic HBV infections. PMID:19406163

Thibault, Vincent; Laperche, Syria; Akhavan, Sepideh; Servant-Delmas, Annabelle; Belkhiri, Dalila; Roque-Afonso, Anne-Marie

2009-08-01

139

Liver cancer-related gene CYP2E1 expression in HBV transgenic mice with acute liver injury.  

PubMed

The objective of this research was to study the CYP2E1 gene expression in carbon tetrachloride (CCl4)-induced acute liver injury in hepatitis B virus (HBV) transgenic mice. Twenty-four HBV (-) and 24 HBV (+) transgenic mice aged 8 to 10 weeks were selected for the present study. Intraperitoneal injection of 1.0 ?L/g of CCl4 (1:4 dissolved in olive oil) to mice was performed to induce acute liver injury model. Eight normal clean-grade C57BL/6 mice were taken as the control group. The control group received saline intraperitoneally. The mice in each group were killed 3, 6, 12, 24, 48, and 72 h after injection. The liver tissue samples of mice were collected. The liver histological changes at different time points in each group were observed under light microscope. The quantitative PCR methods were utilized to measure the relative mRNA levels of CYP2E1 gene in liver tissues. Immunohistochemistry and Western blot techniques were used to observe tissue expression levels of CYP2E1 in each group. Compared with that of the control group, mRNA and protein expression levels of CYP2E1 significantly increased both in the HBV (-) group and in the HBV (+) group after the CCl4 induced the acute liver injury, and it reached the peak at 72 h after the CCl4 injection. Compared with the HBV (-) group, the mice in the HBV (+) group had severe liver damage and significantly increased CYP2E1 gene and protein expression levels. In the CCl4-induced acute liver injury of HBV transgenic mice, the CYP2E1 gene expression significantly increased. The results provided evidence for the HBV-induced liver damage and liver cancer pathogenesis. PMID:24318994

Zhang, Chun; Wei, Qin; Jiang, Tao; Shou, Xi; Li, Zhi-Qiang; Wen, Hao

2014-04-01

140

HBx Down-Regulated Gld2 Plays a Critical Role in HBV-Related Dysregulation of miR-122  

PubMed Central

miR-122 is a liver-rich-specific microRNA that plays an important role in hepatic gene expression via post-transcription regulation, and it is potentially associated with the development of hepatocellular carcinoma. It has been confirmed that miR-122 is down-regulated during HBV infection; however, how HBV affects miR-122 is still debated. One research provided evidence that HBx could reduce the miR-122 transcription level, but the other insisted that HBV had no significant effect on miR-122 transcription level but reduce miR-122 level via binding and sequestering endogenous miR-122. It is determinate that Gld2 could increase the specific miRNA stabilization by monoadenylation which was a post-transcription regulation. In this study, we aimed to investigate the mechanism of HBV-induced reduction of miR-122 and examine whether Gld2 is involved in it. According to the results of a microRNA microarray, we found miR-122 was the most down-regulated microRNA in HepG2.2.15 compared to HepG2. As revealed by qRT-PCR and western blotting analyses, both miR-122 and Gld2 levels were reduced in hepatic cell lines with expression of HBV or HBx but not other proteins of HBV, and over-expression of Gld2 could abolish the effect of HBV and HBx on the miR-122 level. What's more, both HBV and HBx have no significant effect on pre-miR-122 levels. And the dual-luciferase assay implicated that HBx could reduce the Gld2 promoter activity but had no significant effect on miR-122 promoter activity. In conclusion, HBx is a critical protein derived from HBV, which regulates miR-122 via down-regulating Gld2.

Peng, Feng; Xiao, Xinqiang; Jiang, Yongfang; Luo, Kaizhong; Tian, Yi; Peng, Milin; Zhang, Min; Xu, Yun; Gong, Guozhong

2014-01-01

141

HBx down-regulated Gld2 plays a critical role in HBV-related dysregulation of miR-122.  

PubMed

miR-122 is a liver-rich-specific microRNA that plays an important role in hepatic gene expression via post-transcription regulation, and it is potentially associated with the development of hepatocellular carcinoma. It has been confirmed that miR-122 is down-regulated during HBV infection; however, how HBV affects miR-122 is still debated. One research provided evidence that HBx could reduce the miR-122 transcription level, but the other insisted that HBV had no significant effect on miR-122 transcription level but reduce miR-122 level via binding and sequestering endogenous miR-122. It is determinate that Gld2 could increase the specific miRNA stabilization by monoadenylation which was a post-transcription regulation. In this study, we aimed to investigate the mechanism of HBV-induced reduction of miR-122 and examine whether Gld2 is involved in it. According to the results of a microRNA microarray, we found miR-122 was the most down-regulated microRNA in HepG2.2.15 compared to HepG2. As revealed by qRT-PCR and western blotting analyses, both miR-122 and Gld2 levels were reduced in hepatic cell lines with expression of HBV or HBx but not other proteins of HBV, and over-expression of Gld2 could abolish the effect of HBV and HBx on the miR-122 level. What's more, both HBV and HBx have no significant effect on pre-miR-122 levels. And the dual-luciferase assay implicated that HBx could reduce the Gld2 promoter activity but had no significant effect on miR-122 promoter activity. In conclusion, HBx is a critical protein derived from HBV, which regulates miR-122 via down-regulating Gld2. PMID:24667324

Peng, Feng; Xiao, Xinqiang; Jiang, Yongfang; Luo, Kaizhong; Tian, Yi; Peng, Milin; Zhang, Min; Xu, Yun; Gong, Guozhong

2014-01-01

142

Dealing with Pro Se Patrons  

ERIC Educational Resources Information Center

The problem of the "pro se" patrons (people who are representing themselves in a legal dispute or transaction) has received significant attention in the legal information literature, and many excellent suggestions have been offered to aid law librarians in dealing with this population group. However, these suggestions can be usefully applied in…

Pettinato, Tammy R.

2008-01-01

143

Inhibition of Hepatitis B Virus Replication by Helper Dependent Adenoviral Vectors Expressing Artificial Anti-HBV Pri-miRs from a Liver-Specific Promoter  

PubMed Central

Research on applying RNA interference (RNAi) to counter HBV replication has led to identification of potential therapeutic sequences. However, before clinical application liver-specific expression and efficient delivery of these sequences remain an important objective. We recently reported short-term inhibition of HBV replication in vivo by using helper dependent adenoviral vectors (HD Ads) expressing anti-HBV sequences from a constitutively active cytomegalovirus (CMV) promoter. To develop the use of liver-specific transcription regulatory elements we investigated the utility of the murine transthyretin (MTTR) promoter for expression of anti-HBV primary microRNAs (pri-miRs). HD Ads containing MTTR promoter effected superior expression of anti-HBV pri-miRs in mice compared to HD Ads containing the CMV promoter. MTTR-containing HD Ads resulted in HBV replication knockdown of up to 94% in mice. HD Ads expressing trimeric anti-HBV pri-miRs silenced HBV replication for 5 weeks. We previously showed that the product of the codelivered lacZ gene induces an immune response, and the duration of HBV silencing in vivo is likely to be attenuated by this effect. Nevertheless, expression of anti-HBV pri-miRs from MTTR promoter is well suited to countering HBV replication and development of HD Ads through attenuation of their immunostimulatory effects should advance their clinical utility.

Mowa, Mohube Betty; Crowther, Carol; Ely, Abdullah; Arbuthnot, Patrick

2014-01-01

144

HBV and HCV infection, polyarteritis nodosa and mixed cryoglobulinaemia: a case report.  

PubMed

HCV infection has been associated with a broad spectrum of extrahepatic manifestations. In some of these, such as mixed cryoglobulinaemia (MC), the association is firmly established, whereas in others, such as polyarteritis nodosa (PAN), it is anecdotal; in fact, in this disorder the importance of the association is controversial, since it seems to be related to the frequent coinfection of HBV and HCV. The pathogenesis of MC and PAN is far from clear, but recent developments have added a plethora of information on the mechanisms underlying these disorders. Although both could be induced by a viral infection, the pathophysiological processes underlying the two diseases are different. We describe the occurrence in the same patient of HBV-related PAN and HCV-related MC. PMID:11147768

Della Rossa, A; Tavoni, A; Lorefice, P; Casula, F; Bombardieri, S

2000-01-01

145

Modeling the effects of covalently closed circular DNA and dendritic cells in chronic HBV infection.  

PubMed

The contribution of covalently closed circular DNA (cccDNA) and dendritic cells (DCs) to the progression of chronic hepatitis B virus (HBV) infection remains largely unknown. A dynamic model with seven cell types was proposed based on the biological mechanisms of viral replication and the host immune response. The cccDNA self-amplification rate was found to be closely related to both the basic reproduction number of the virus and the immune response. The combination of the cccDNA self-amplification rate and the initial activated DC count induces rich dynamics. Applying our model to the clinical data of untreated patients, we found that chronic patients have a high cccDNA self-amplification rate. For antiviral treatment, an overall drug effectiveness was introduced and the critical drug effectiveness was obtained. The model predicts that timely long-term therapy is needed to reduce the symptoms of HBV and to maintain the benefits of treatment. PMID:24816182

Li, Qiang; Lu, Furong; Deng, Guohong; Wang, Kaifa

2014-09-21

146

Seroprevalence of HBV, HCV & HIV Co-Infection and Risk Factors Analysis in Tripoli-Libya  

PubMed Central

Background In 1998 Libya experienced a major outbreak of multiple blood borne viral hepatitis and HIV infections. Since then, no studies have been done on the epidemic features and risk factors of HBV, HCV, HIV and co-infection among the general population. Methods A prospective study was carried out using a multi-centre clustering method to collect samples from the general population. The participants were interviewed, and relevant information was collected, including socio-demographic, ethnic, and geographic variables. This information was correlated with the risk factors involved in the transmission of HBV, HCV and HIV. Blood samples were collected and the sera were tested for HBsAg, anti-HCV and anti-HIV using enzyme immunoassay. Results A total of 9,170 participants from the nine districts of Tripoli were enrolled. The average prevalence of HBsAg was 3.7%, anti-HCV 0.9%, anti-HIV 0.15% and co-infection 0.02%. The prevalence varied from one district to another. HBV was more prevalent among those aged over 50 years and was associated with family history. Anti-HCV and anti-HIV were more prevalent among those aged 20–40 years. Intravenous drug use and blood transfusion were the main risk factors for HCV and HIV infection. Conclusion HBV, HCV, HIV and co-infection are relatively common in Libya. High prevalence was associated with geographic, ethnic and socioeconomic variability within the community. HCV and HIV infections among the younger age groups are becoming an alarming issue. Regulations and health care education need to be implemented and longer term follow-up should be planned.

Daw, Mohamed A.; Shabash, Amira; El-Bouzedi, Abdallah; Dau, Aghnya A.

2014-01-01

147

[Research on HBV DNA inhibition of plasmid acute infection mouse with betulinic acid].  

PubMed

Betulinic acid is a naturally occurring pentacyclic triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory properties. The purpose of this study is to investigate the HBV DNA replication inhibition in the mouse model with betulinic acid. Hydrodynamic injection method via the tail vein with the Paywl. 3 plasmid was used to establish the animal mode (n = 15), and the mice were randomly divided into the PBS control group (n = 5), Betulinic acid treatment group (n = 5) and lamivudine control group (n = 5). The day after successful modeling , the mice would have taken Betulinic acid (100 mg x kg(-1)), lamivudine (50 mg x kg(-1)), PBS drugs orally, once daily for 7 days, blood samples were acquired from the orbital venous blood at 3, 5, 7 days after the administering, HBsAg and HBeAg in serum concentration were measured by ELISA and the mice were sacrificed after 7 days, HBV DNA southern detections were used with part of mice livers. The results showed that betulinic acid significantly inhibited the expression of HbsAg in the mice model at the fifth day compared with the control group, and there was no significant differences between the effects of lamivudine and the PBS control group; both the betulinic acid and lamivudine groups had no significant inhibition for the HBeAg expression; the HBV DNA expressions of the liver tissue from the betulinic acid and lamivudine groups were inhibited compared with the control group. Taken together, these results reveal betulinic acid can inhibit the HBsAg expression and replication of the liver HBV DNA in the mouse model. PMID:24956858

Qiao, Bing; Gao, Yue-Qiu; Li, Man; Wu, Shao-Fei; Zheng, Chao; Jin, Shu-Gen; Wu, Hui-Chun; Yu, Zhuo; Sun, Xue-Hua

2014-03-01

148

Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients  

Microsoft Academic Search

Hepatitis B surface antigen (HBsAg)-positive kidney transplant recipients have increased liver-related mortality. The impact of lamivudine treatment on patient survival, the optimal time to start treatment, and the feasibility of discontinuing treatment have not been determined. This study examined these issues with a novel management protocol. Serum hepatitis B virus (HBV) DNA levels were measured serially in HBsAg-positive kidney transplant

Tak Mao Chan; Guo Xiang Fang; Colin S. O. Tang; Ignatius K. P. Cheng; Kar Neng Lai; Stephen K. N. Ho

2002-01-01

149

Viral hepatitis: review of arthritic complications and therapy for arthritis in the presence of active HBV/HCV.  

PubMed

Chronic infection with hepatitis B (HBV) or C (HCV) virus, which currently affect approximately 7 % of the world population, is encountered with the same frequency among patients with arthritis starting biological or non-biological disease-modifying anti-rheumatic drugs (DMARDs). Treatment with biological agents, including anti-tumor necrosis factor agents, rituximab, and abatacept, without appropriate antiviral therapy has been associated with reactivation of HBV infection which in some cases can lead to life-threatening complications, indicating the need for appropriate screening and treatment of these patients. In this review, the latest data regarding HBV or HCV-related arthritic complications and treatment of rheumatic diseases in the presence of chronic HBV or HCV infection will be critically presented. PMID:23436024

Vassilopoulos, Dimitrios; Calabrese, Leonard H

2013-04-01

150

HBV infection among pre-school children in Naples (Italy) and the role of intrafamily contact.  

PubMed

In the Neapolitan area the prevalence of adult HBsAg carriers ranges from 4-7%. Moreover, hepatitis B virus (HBV) is responsible for most of the chronic hepatitis cases in childhood. Since the chronic carrier state in our area is acquired by early horizontal contact, we investigated the prevalence of HBV infection among 207 pre-school children and of HBsAg carriers among their family members. None of the children was found to be HBsAg positive and 3.9% of them had anti-HBs. HBsAg was positive in 29 out of 892 (3.3%) of the family members. There was a clear age-related distribution of the carriers, their prevalence reaching 6.7% among the elderly members. On the whole, 19 out of the 207 index cases had at least one HBsAg carrier in their family. The results suggest that in our area a decline of HBV endemia may be under way and that early intrafamily contact is no more a common pathway in acquiring an HBsAg carrier state. PMID:2247586

Gaeta, G B; De Fraia, M; Sardaro, C; Giusti, G

1990-09-01

151

Effect of Trichinella spiralis infection on the immune response to HBV vaccine in a mouse model.  

PubMed

Vaccination is the most effective and cost-effective way to treat hepatitis B virus (HBV) infection. Collective data suggest that helminth infections affect immune responses to some vaccines. Therefore, it is important to reveal the effects of helminth infections on the efficacy of protective vaccines in countries with highly prevalent helminth infections. In the present work, effects of Trichinella spiralis infection on the protective efficacy of HBV vaccine in a mouse model were investigated. This study demonstrated that the enteric stage of T. spiralis infection could inhibit the proliferative response of spleen lymphocytes to hepatitis B surface antigen (HBsAg) and lead to lower levels of anti-HBsAg antibodies, interferon-?, and interleukin (IL)-2, along with higher levels of IL-4 and IL-5. However, these immunological differences are absent in the muscle stage of T. spiralis infection. The results suggest that the muscle stage of T. spiralis infection does not affect the immune response to HBV vaccination, while the enteric-stage infection results in a reduced immune response to HBsAg. PMID:23883369

Guan, Fei; Hou, Xiao; Nie, Ge; Xiao, Yan; Zhang, Qi; Liu, Wen-qi; Li, Yong-long; Lei, Jia-hui

2013-10-01

152

Torrential rainfall event in Genoa: Coupled WRF-NMM and HBV model  

NASA Astrophysics Data System (ADS)

On November 4 th, 2011, the city of Genoa was affected by a torrential convective rainfall episode. The finger-shape mesoscale system remained stationary for a significant number of hours on the same area of few square kilometers. About 500 millimeters of rain, one third of the average annual precipitation amount, fell in approximately six hours. A flash flood occurred in the Bisagno river and Fereggiano creek, causing six causalities and the inundation of the Brignole area. For the catchments, where flood events usually occur in a few hours time and peak discharge generally last only a few minutes, it is necessary to use high resolution meteorological data as an input to hydrological model. The effectiveness of flood warning is dependent on the forecast accuracy of certain physical parameters, such as the peak magnitude of the flood, its timing, location and duration. The conceptual HBV rainfall - runoff models enable the estimation of these parameters and provide useful operational forecasts. This paper presents the results of coupled meteorological WRF-NMM and hydrological HBV model. Hourly quantitative precipitation forecasts, for three days ahead, were used as input to the conceptual hydrological model. HBV model was able to predict significant increase of water level with exceedance of regular defence level and exact time of the flood peak on the observed hydrological profile even weather forecast model wasn't successful in the predicition of the hourly amount of precipitation.

Ivkovic, Marija; Dekic, Ljiljana; Mihalovic, Ana

2013-04-01

153

HBV infection of cell culture: evidence for multivalent and cooperative attachment  

PubMed Central

Hepadnaviruses do not infect cultured cells, therefore our knowledge of the mechanism of the early stages of virus–cell interaction is rather poor. In this study, we show that dimethylsulfoxide (DMSO)-treated HepG2 hepatoblastoma cells are infected efficiently by serum-derived hepatitis B virus (HBV) as monitored by viral gene expression and replication markers. To measure virus attachment, a variety of HBV surface proteins (HBsAgs) were conjugated to polystyrene beads and their capacity to attach cells was visualized and quantified by light microscopy at a single-cell resolution. Remarkably, DMSO increases the attachment efficiency by >200-fold. We further identify the QLDPAF sequence within preS1 as the receptor-binding viral domain epitope. Interestingly, a similar sequence is shared by several cellular, bacterial and viral proteins involved in cell adhesion, attachment and fusion. We also found that the small HBsAg contains a secondary attachment site that recognizes a distinct receptor on the cell membrane. Furthermore, we provide evidence in support of multivalent HBV attachment with synergistic interplay. Our data depict a mechanistic view of virus attachment and ingestion.

Paran, Nir; Geiger, Benjamin; Shaul, Yosef

2001-01-01

154

An oligonucleotide microarray for multiplex real-time PCR identification of HIV-1, HBV, and HCV.  

PubMed

We describe a novel microarray-based approach for simultaneous identification and quantification of human immunodeficiency virus type 1 (HIV-1) and hepatitis B and C viruses (HBV and HCV) in donor plasma specimens. The method is based on multiplex real-time RT-PCR performed within the microarray hydrogel pads. Double-stranded amplification products are simultaneously detected using nonspecific SYBR Green I dye due to the reaction run in separate pads bearing 5'-immobilized specific primers. Both the sensitivity and specificity of the assay, based on 132 blood specimens analyzed, were 100% (56, 26, and 8 specimens were seropositive to HBV HCV and HIV-1, respectively; 22 were positive to both HIV-1 and HCV and 2 positive to all three viruses; 18 samples were pathogen-negative). The dynamic range of the quantitative analysis covered a six-order interval ranging from 100 to 106 genome equivalents per assay. The 95% detection limits were 14 gEq for HIV-1, 10 gEq (1.7 IU) for HBV, and 15 gEq (7.5 IU) for HCV per assay. The proposed approach is considered to be versatile and could be adapted for simultaneous identification and quantification of numerous genetic targets. PMID:18330353

Khodakov, Dmitry A; Zakharova, Natalia V; Gryadunov, Dmitry A; Filatov, Felix P; Zasedatelev, Alexander S; Mikhailovich, Vladimir M

2008-02-01

155

Genomic characterization of HBV genotype F in Bolivia: genotype F subgenotypes correlate with geographic distribution and T 1858 variant  

Microsoft Academic Search

Summary.  Hepatitis B virus (HBV) strains were classified into eight genotypes from A to H. Genotype F, an indigenous genotype in Central\\u000a and South America, has been classified into subgenotypes. An in-depth phylogenetic analysis was performed using two full-length\\u000a Bolivian HBV sequences and other genotype F strains from the database. A novel nomenclature of subgenotypes of genotype F\\u000a was proposed, in

T. T. T. Huy; H. Ushijima; T. Sata; K. Abe

2006-01-01

156

Viral determinants predicting hepatitis B surface antigen (HBsAg) seroclearance in HIV-/HBV-coinfected patients.  

PubMed

The aim of this retrospective study was the identification of clinically useful viral determinants for the prediction of hepatitis B surface antigen (HBsAg) seroclearance and sustained virological response in hepatitis B virus/human immunodeficiency virus (HBV-/HIV)-coinfected patients receiving HBV-active combined antiretroviral therapy (cART). Quantification of HBsAg, HBeAg and HBV DNA before and after initiation of HBV-active cART in a cohort of 59 HIV-/HBV-coinfected patients was performed. Calculations of receiver operating characteristics (ROC) and Kaplan-Meier analysis were used for the identification of predictors of HBsAg seroclearance for HBeAg-positive [HBeAg(+); n = 36] and HBeAg-negative [HBeAg(-);n = 23] patients. HBeAg(+) patients with an HBsAg on-treatment decline ?1 log IU/mL per year achieved higher HBsAg loss rates (P = 0.0294), whereas the quantification of HBeAg had no predictive value for HBsAg seroclearance. Among HBeAg(-) patients, a pretreatment baseline cut-off level of HBsAg ?100 IU/mL was highly predictive for HBsAg seroclearance. No significant influence of the HBV genotype on HBsAg seroclearance was observed among the entire cohort. Quantitative determination of HBsAg provides a clinically useful viral parameter for the prediction of HBsAg seroclearance both in HBeAg(+) and HBeAg(-) HIV-/HBV-coinfected patients receiving HBV-active cART. PMID:24112778

Strassl, R; Reiberger, T; Honsig, C; Payer, B A; Mandorfer, M; Grabmeier-Pfistershammer, K; Rieger, A; Kundi, M; Grundtner, P; Peck-Radosavljevic, M; Popow-Kraupp, T

2014-07-01

157

Risk of HBV liver disease in isolated antiHbc patients receiving immuno-chemotherapy for non Hodgkin lymphoma  

Microsoft Academic Search

1 in order to clarify the risk of HBV-related liver disease in a large number of isolated anti-HBc positive patients undergoing chemo- immunosuppressive therapy for non-Hodgkin's lym- phoma. So far only limited case reports have been pub- lished about this issue and no data on HBV-related risk in this population was available. While the need of antiviral prophylaxis is well

C. Targhetta; M. G. Cabras; E. Angelucci

2008-01-01

158

Clinical Course of Lamivudine Monotherapy in Patients with Decompensated Cirrhosis due to HBeAg negative chronic HBV infection  

Microsoft Academic Search

OBJECTIVES:We have evaluated the efficacy of long-term lamivudine monotherapy in patients with decompensated HBeAg-negative\\/HBV-DNA positive cirrhosis.METHODS:We analyzed the clinical course and outcome of lamivudine treatment in 30 consecutive cirrhotics and compared with 30 HBV untreated historical HBeAg-negative controls matched for age and gender.RESULTS:Significant clinical improvement, defined as a reduction of at least two points in Child-Pugh score was observed in

Spilios Manolakopoulos; Stylianos Karatapanis; Jiannis Elefsiniotis; Nicoletta Mathou; Jiannis Vlachogiannakos; Elissabet Iliadou; Anastasios Kougioumtzan; Michalis Economou; Christos Triantos; Dimitrios Tzourmakliotis; Alec Avgerinos

2004-01-01

159

Association between metabolic abnormalities and HBV related hepatocelluar carcinoma in Chinese: A cross-sectional study  

PubMed Central

Background Previous studies suggested that the abnormality of metabolism is a newly identified risk factor in HBV-related hepatocellular carcinoma (HCC). The association between metabolic factors and hepatocellular carcinoma (HCC) has not been clarified up to now. This study was conducted to investigate the prevalence of metabolic abnormalities in HCC and to probe the association between metabolic parameters and liver function as well, so as to evaluate the interactions between metabolism and the development of HBV-related HCC. Methods Totally 179 cases of HBV-related HCC, who were surgically treated and pathologically confirmed were enrolled. HBV carriers (n = 100) and healthy controls (n = 150) were recruited from routine physical examination during the same period. Body mass index (BMI) was obtained from medical documentation. All the metabolic-related parameters and liver function tests were determined with routine biochemical or immunological analytic methods. Malondialdehyde (MDA) and total antioxidant capacity(TAOC)were detected by chemical analytic methods. A stratified analysis was conducted according to BMI, glycated albumin (GA), free fatty acids (FFA), and the relationships between the metabolic-related parameters and liver functions were analyzed in HCC and control subjects. Results HCC group showed significantly high levels of mean BMI, serum glucose, low serum lipids levels than controls (P < 0.05). Acquired by stratified analysis, the higher the BMI, the higher level of insulin and homeostasis model assessment for insulin resistance (HOMA-IR) (P < 0.01) were found in HCC patients. Elevated level of MDA and ?-glutamyltransferase (GGT) were revealed in those with high serum FFA level for the first time. Strong associations between metabolic factors and liver function were shown in HCC (P < 0.05). Higher GA level was strongly associated with increased risk of cancer compared to healthy controls (OR = 9.87, 95% confidence interval: 1.86~52.29). Serum triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels were negative contributory factors for HCC (OR = 0.05, 95% confidence interval: 0.01~0.27 and OR = 0.32, 95% confidence interval, 0.11~0.95: respectively). Conclusions Metabolic abnormalities are closely associated with the occurrence and development of HBV-related HCC. Oxidative stress and/or lipid peroxidation might be involved in the pathogenesis and acceleration of liver function impairments in HCC.

2011-01-01

160

Prevalence of hepatitis B virus (HBV) infection in Singapore men with sexually transmitted diseases and HIV infection: role of sexual transmission in a city state with intermediate HBV endemicity.  

PubMed Central

STUDY OBJECTIVES--To describe the prevalence of hepatitis B virus (HBV) infection in patients with sexually transmitted diseases (STD) and human immunodeficiency virus (HIV) infection, and to determine the role of sexual transmission of HBV infection in Singapore. DESIGN--A cross sectional study of all consecutive men presenting with a new episode of STD at a government outpatient clinic and all men with HIV infection on routine follow up at a government hospital. The prevalence of various HBV markers was compared with that of healthy males aged 15 years and above (controls). SETTING--Singapore, a city state of intermediate HBV endemicity. SUBJECTS--These comprised 497 STD patients, 47 HIV infected patients, and 418 controls. MAIN RESULTS--The overall seroprevalences of HBV infection in STD patients, HIV infected patients, and control subjects were 41.2%, 61.7%, and 33.3%, respectively (p < 0.001). The seroprevalences of hepatitis B surface antigen (6.2%, 8.5%, and 4.5%, respectively) were comparable in the three groups. Using stepwise logistic regression analysis, the adjusted seroprevalences of HBV infection in STD and HIV infected patients were respectively 2.4 times (95% confidence interval (CI), 1.7, 3.3) and 3.3 times (95% CI 1.7, 6.3) higher than in controls. HBV infection rates were higher among Chinese (odds ratio (OR), 1.9; 95% CI 1.6, 3.4) than non-Chinese, and among those aged 25-34 years (OR 2.4; 95% CI 1.6, 3.4), 35-44 years (OR 3.9; 95% CI 2.5, 5.9), and 45+ years (OR 6.2; 95% CI 3.8, 10.2) than in those aged 15-24 years. Sex related factors significantly associated with higher infection rates, independent of age and ethnic group, were reactive VDRL test (OR 2.4; 95% CI 1.2, 4.7), participation in anal intercourse (OR 2.3; 95% CI 1.2, 4.3), and having 10 or more lifetime sexual partners (OR 1.5; 95% CI, 1.0, 2.1). CONCLUSION--The importance of sexual transmission of HBV in an area of intermediate HBV endemicity was confirmed. Patients attending STD clinics should be routinely screened for HBV markers and those found to be seronegative should be strongly advised to be immunised against this virus.

Heng, B H; Goh, K T; Chan, R; Chew, S K; Doraisingham, S; Quek, G H

1995-01-01

161

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

PubMed Central

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.

Chu, Fujiang; Zhu, Jiayong

2014-01-01

162

HBV-Specific shRNA is Capable of Reducing the Formation of Hepatitis B Virus Covalently Closed Circular DNA, but has No Effect on Established Covalently Closed Circular DNA in vitro  

PubMed Central

Summary Hepatitis B virus (HBV) covalently closed circular DNA (CCC DNA) is the source of HBV transcripts and persistence in chronically infected patients. The novel aspect of this study was to determine the effect of RNA interference (RNAi) on HBV CCC DNA when administered prior to establishment of HBV replication or during chronic HBV infection. HBV replication was initiated in HepG2 cells by transduction with HBV baculovirus. Subculture of HBV expressing HepG2 cells at 10 days post-transduction generates a system in which HBV replication is ongoing and HBV is expressed largely from CCC DNA thus simulating chronic HBV infection. HepG2 cells were transduced with short hairpin RNA (shRNA) expressing baculovirus prior to initiation of HBV replication or during chronic HBV replication and the levels of HBV RNA, HBsAg, replicative intermediates (RI), extracellular (EC) and CCC DNA species were measured. HBsAg, HBV RNA and DNA levels were markedly reduced through day 8 whether cells were transduced with shRNA prior to or during a chronic infection; however, the CCC DNA species were only affected when shRNA was administered prior to initiation of infection. We conclude that RNAi may have therapeutic value for controlling HBV replication at the level of RI and EC DNA and for reducing establishment of CCC DNA during HBV infection. Our data support previous findings demonstrating the stability of HBV CCC DNA to antiviral therapy. This study also reports the development of a novel HBV baculovirus subculture system that can be used to evaluate antiviral effects on chronic HBV replication.

Starkey, Jason L.; Chiari, Estelle F.; Isom, Harriet C.

2009-01-01

163

Prognostic Values of Fluctuations in Serum Levels of Alanine Transaminase in Inactive Carrier State of HBV Infection  

PubMed Central

Background: Current guidelines introduce periodic monitoring of serum alanine transaminase (ALT) as the first-line modality in follow-up patients, with a hepatitis B virus (HBV) inactive carrier state. Objectives: This study aimed to determine the incidence rate and patterns of ALT fluctuations and prognostic values for the development of chronic HBV e antigen (HBeAg)-negative hepatitis B (CHB), HBV surface antigen (HBsAg) seroclearance, and liver-related complications. Patients and Methods: Treatment-naïve patients with a chronic HBV infection, HBeAg(-)/HBeAb(+), normal ALT levels, and HBV DNA < 2000 IU/mL, were followed-up every 6-12 months by assessing serum ALT levels. Serum HBV DNA was measured in cases of elevated ALT levels. Results: A total of 399 patients were followed-up for 8.9 years; ALT > upper limit of normal (ULN, i.e. 40 IU/L) was detected in 103 (25.8%) patients, with an annual incidence rate of 2.9%. ALT elevation was associated with; male gender, age, and higher serum ALT levels at study entry. Among the cases of ALT elevations, 16 (15.5%) patients had ALT levels > 2 × ULN. There were 38 (36.9%) patients who had ALT levels that remained > ULN over six months, and 21 (20.4%) patients experienced at least two episodes of ALT elevations. In 15 (14.6%) patients, elevated ALT levels were associated with increased HBV replication (i.e. HBV DNA > 2 000 IU/mL) and these were considered as CHB. However, elevation of ALT levels, even in the absence of HBV replication, increased the risk for the development of CHB up to 8-fold in prospective follow-ups. HBsAg seroclearance, cirrhosis, and hepatocellular carcinoma were detected in 43 (10.8%), 4 (1%), and 1 (0.25%) patients, respectively. Conclusions: Fluctuations in serum ALT levels may change the prognosis of a HBV inactive carrier state.

Farzi, Hossein; Ebrahimi Daryani, Nasser; Mehrnoush, Leila; Salimi, Shima; Alavian, Seyed Moayed

2014-01-01

164

Potentially functional genetic variants in microRNA processing genes and risk of HBV-related hepatocellular carcinoma.  

PubMed

Genetic variations in miRNA processing genes may affect the biogenesis of miRNA, hence risk of HBV infection and hepatocellular carcinoma (HCC) development. In the present study, we hypothesized that potentially functional polymorphisms in 3'-untranslated region (UTR) of miRNA processing genes might contribute to susceptibility of HBV infection and HCC development. To test the hypothesis, we genotyped three selected SNPs (rs1057035 in DICER1, rs3803012 in RAN, and rs10773771 in PIWIL1) in a case-control study of 1300 HBV-positive HCC cancer cases, 1344 HBV persistent carriers, and 1344 HBV natural clearance subjects in Chinese. We observed that DICER1 rs1057035 CT/CC variant genotypes were associated with a significant decreased risk of HCC (adjusted OR = 0.79, 95% CI = 0.64-0.96) compared with wild-type TT and RAN rs3803012 AG/GG variant genotypes increased the risk of HBV persistent infection compared with AA genotype (adjusted OR = 1.35, 95% CI = 1.03-1.77). However, PIWIL1 rs10773771 CT/CC variant genotypes were associated with an approaching decreased risk of HCC (adjusted OR = 0.86, 95% CI = 0.73-1.01) and similar with RAN rs3803012 AG/GG (adjusted OR = 0.80, 95% CI = 0.61-1.06). Furthermore, reporter gene assays indicated that the three SNPs (rs1057035, rs3803012, and rs10773771) might change the binding ability of miRNAs to the 3'UTR of the three genes (DICER1, RAN, and PIWIL1), respectively. These findings indicated that DICER1 rs1057035, RAN rs3803012, and PIWIL1 rs10773771 might contribute to the risk of HBV-related HCC. PMID:23868705

Liu, Li; An, Jiaze; Liu, Jibin; Wen, Juan; Zhai, Xiangjun; Liu, Yao; Pan, Shandong; Jiang, Jie; Wen, Yang; Liu, Zheng; Zhang, Yixin; Chen, Jianguo; Xing, Jinliang; Ji, Guozhong; Shen, Hongbing; Hu, Zhibin; Fan, Zhining

2013-11-01

165

Forecasting river discharge using coupled WRF-NMM meteorological model and HBV runoff model, case studies  

NASA Astrophysics Data System (ADS)

This paper examines two episodes of heavy rainfall and significantly increased water levels. The first case relates to the period including the beginning and the end of the third decade of June 2010 at the Kolubara river basin, where extreme rainfall led to two big flood waves on the Kolubara river, whereat water levels exceeded both regular and extraordinary flood defence and approached their historical maximum. The second case relates to the period including the end of November and the beginning of December 2010 at the Jadar river basin, where heavier precipitation caused the water levels of the basin to reach and surpass the occurrence limit (warning level). The HBV (Hydrological Bureau Waterbalance-section) rainfall/snowmelt - runoff model installed at the RHMSS uses gridded quantitative precipitation and air temperature forecast for 72 hours in advance based on meteorological weather forecast WRF-NMM mesoscale model. Nonhydrostatic Mesoscale Model (NMM) core of the Weather Research and Forecasting (WRF) system is flexible state-of-the-art numerical weather prediction model capable to describe and estimate powerful nonhydrostatic mechanism in convective clouds that cause heavy rain. The HBV model is a semi-distributed conceptual catchment model in which the spatial structure of a catchment area is not explicitly modelled. Instead, the sub-basin represents a primary modelling unit while the basin is characterised by area-elevation distribution and classification of vegetation cover and land use distributed by height zone. WRF-NMM forecast shows very good agreement with observations in terms of timing, location and amount of precipitation. They are used as input for HBV model, forecasted discharges at the output profile of the selected river basin represent model output for consideration. 1 Republic Hydrometeorological Service of Serbia

Deki?, L.; Mihalovi?, A.; Jovi?i?, I.; Vladikovi?, D.; Jerini?, J.; Ivkovi?, M.

2012-04-01

166

Prevalence of HBV, HDV, HCV, and HIV infection during pregnancy in northern Benin.  

PubMed

Pregnant women are not screened for HBsAg and anti-HCV antibodies in many African countries. As there are few data concerning the prevalence of HBV, HDV, and HCV serological markers in Benin, the aim of this study was to evaluate their 2011 prevalence in pregnant women undergoing HIV screening in a rural area of north Benin, and compare the data with those reported for the same area in 1986. The sera of 283 women were examined for HBsAg, anti-HBs, anti-HBc, anti-HCV, and anti-HIV 1/2 antibodies. In the case of HBsAg positivity, a search was made for the HBeAg, anti-HDV, and HBV genotypes; in the case of anti-HCV positivity, a search was made for the HCV genotypes. HBsAg, anti-HBs, anti-HBc, anti-HCV, and anti-HIV 1/2 were positive in respectively 44 (15.5%), 82 (29.0%), 234 (82.7%), 21 (7.4%), and nine samples (3.2%). Of the HBsAg-positive samples, five (11.4%) were positive for HBeAg, five (11.4%) for anti-HDV, and 19 for HBV genotype E. Of the anti-HCV-positive samples, five were positive for genotype 2a/2c and one for genotype 1a. The prevalence of anti-HBc alone (HBsAg and anti-HBs negative) was very high (41.3%). In comparison with the 1986 data, the prevalence of HBsAg and anti-HBc remained unchanged, that of HBeAg and anti-HDV had decreased, and that of anti-HIV 1/2 had increased. As these data confirm that HBV and HCV are highly endemic in the study area, it may be appropriate to introduce HBsAg and anti-HCV screening for pregnant women. J. Med. Virol. 86:1281-1287, 2014. © 2014 Wiley Periodicals, Inc. PMID:24777580

De Paschale, Massimo; Ceriani, Cristina; Cerulli, Teresa; Cagnin, Debora; Cavallari, Serena; Ndayaké, Joseph; Zaongo, Dieudonné; Priuli, Gianbattista; Viganò, Paolo; Clerici, Pierangelo

2014-08-01

167

Case report Unusual selection of rtA181V HBV mutants cross- resistant to adefovir following prolonged lamivudine monotherapy: report of two cases  

Microsoft Academic Search

Development of hepatitis B virus (HBV)-resistant strains following nucleos(t)ide analogue treatment is a major concern. The A181V mutation within the reverse transcrip- tase (RT) of HBV has been shown to be associated with HBV resistance to adefovir dipivoxil (ADV), and its level of sensitivity to other nucleos(t)ide analogues is an impor- tant issue. This article reports two cases of chronically

Rene Gerolami; Marc Bourliere; Philippe Colson; Philippe Halfon; Patrick Borentain; Mireille Henry; Daniele Botta; Vincent Thibault; Hacene Khiri; Catherine Tamalet

168

Production of recombinant HIV1\\/HBV virus-like particles in Nicotiana tabacum and Arabidopsis thaliana plants for a bivalent plant-based vaccine  

Microsoft Academic Search

Human immunodeficiency virus (HIV-1) and hepatitis B virus (HBV) spread via similar transmission pathways, and infection by HBV occurs in up to 32% of HIV-1 cases. Here, we describe the successful expression of novel recombinant HIV-1\\/HBV virus-like particles (VLPs) in Nicotiana tabacum and Arabidopsis thaliana. The production levels and quality of the recombinant VLPs were comparable in the two plants,

Raffaella Greco; Marie Michel; Denise Guetard; Minerva Cervantes-Gonzalez; Nilla Pelucchi; Simon Wain-Hobson; Francesco Sala; Monica Sala

2007-01-01

169

Association of T-Cell Immunoglobulin and Mucin Domain-Containing Molecule 3 (Tim-3) Polymorphisms with Susceptibility and Disease Progression of HBV Infection  

PubMed Central

Purpose T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) plays an important role in regulating T cells in hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). However, few researches have reported the association of Tim-3 genetic variants with susceptibility and progression of HBV infection. In this study, we focused on the association of Tim-3 polymorphisms with HBV infection, HBsAg seroclearance and hepatocellular carcinoma. Methods A total of 800 subjects were involved in this study. Four groups were studied here, including HBV, HBsAg seroclearance, HBV-associated HCC and healthy controls. Three single-nucleotide polymorphisms (SNPs) of Tim-3, rs246871, rs25855 and rs31223 were genotyped to analyze the association of Tim-3 polymorphisms with susceptibility and disease progression of HBV infection. Results Our study found that rs31223 and rs246871 were associated with disease progression of HBV infection, while none of the three SNPs was relevant to HBV susceptibility. The minor allele “C” of rs31223 was found to be associated with an increased probability of HBsAg seroclearance (P?=?0.033) and genotype “CC” of rs246871 to be associated with an increased probability of HBV-associated HCC (P?=?0.007). In accordance, haplotypic analysis of the three polymorphisms also showed that the haplotype block CGC* and TGC* were significantly associated with HBsAg seroclearance (P<0.05) while haplotype block CAT*, CGT*, TAC* and TGT* were significantly associated with HBV-associated HCC (all P<0.05). Conclusions Genetic variants of Tim-3 have an important impact on disease progression of HBV infection. With specific Tim-3 polymorphisms, patients infected with HBV could be potential candidates of HCC and HBsAg seroclearance.

Liao, Jingyu; Zhang, Qi; Liao, Yun; Cai, Bei; Chen, Jie; Li, Lixin; Wang, Lanlan

2014-01-01

170

Two Classifiers Based on Serum Peptide Pattern for Prediction of HBV-Induced Liver Cirrhosis Using MALDI-TOF MS  

PubMed Central

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.

Song, Wei; Li, Ai-Ling; Wang, Na

2013-01-01

171

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

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.

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

2011-01-01

172

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

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 B(1), 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 1762(T)/1764(A), 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

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

2011-01-01

173

HDAC10 promoter polymorphism associated with development of HCC among chronic HBV patients.  

PubMed

Histone deacetylases (HDACs) are key enzymes responsible for the removal of acetyl groups from acetylated histone and non-histone proteins, and play important roles in various biological processes including transcription regulation and DNA repair. In this study, we identified 22 sequence variants by direct DNA sequencing in 24 individuals and five common variant were selected for genotyping in larger-scale subjects (n=1095). Statistical analysis revealed that HDAC10-589C>T was significantly associated with HCC occurrence among chronic HBV patients (OR=2.39, P(cor)=0.04) as well as HCC acceleration among chronic HBV patients (RH=1.97, Pcor=0.002). Functional assay also revealed that luciferase activity of "T" allele was significantly higher than that of "C" allele of HDAC10-589C>T (P=0.023). These results suggest that the "T" allele of HDAC10-589C>T affect on the increased transcription activity, and might accelerate HCC development through increased expression of HDAC10. PMID:17892858

Park, Byung Lae; Kim, Yoon Jun; Cheong, Hyun Sub; Lee, Soo Ok; Han, Chang Soo; Yoon, Jung-Hwan; Park, Ju Hyun; Chang, Hun Soo; Park, Choon-Sik; Lee, Hyo-Suk; Shin, Hyoung Doo

2007-11-23

174

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

PubMed

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

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

2013-08-01

175

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

PubMed Central

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.

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

1996-01-01

176

Variability in the Precore and Core Promoter Regions of HBV Strains in Morocco: Characterization and Impact on Liver Disease Progression  

PubMed Central

Background Hepatitis B virus (HBV) is one of the most common human pathogens that cause aggressive hepatitis and advanced liver disease (AdLD), including liver cirrhosis and Hepatocellular Carcinoma. The persistence of active HBV replication and liver damage after the loss of hepatitis B e antigen (HBeAg) has been frequently associated with mutations in the pre-core (pre-C) and core promoter (CP) regions of HBV genome that abolish or reduce HBeAg expression. The purpose of this study was to assess the prevalence of pre-C and CP mutations and their impact on the subsequent course of liver disease in Morocco. Methods/Principal Findings A cohort of 186 patients with HBeAg-negative chronic HBV infection was studied (81 inactive carriers, 69 with active chronic hepatitis, 36 with AdLD). Pre-C and CP mutations were analyzed by PCR-direct sequencing method. The pre-C stop codon G1896A mutation was the most frequent (83.9%) and was associated with a lower risk of AdLD development (OR, 0.4; 95% CI, 0.15–1.04; p?=?0.04). HBV-DNA levels in patients with G1896A were not significantly different from the other patients carrying wild-type strains (p?=?0.84). CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were associated with higher HBV-DNA level and increased liver disease severity. Multiple logistic regression analysis showed that older age (?40 years), male sex, high viral load (>4.3 log10 IU/mL) and CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were independent risk factors for AdLD development. Combination of these mutations was significantly associated with AdLD (OR, 7.52; 95% CI, 4.8–8; p<0.0001). Conclusions This study shows for the first time the association of HBV viral load and CP mutations with the severity of liver disease in Moroccan HBV chronic carriers. The examination of CP mutations alone or in combination could be helpful for prediction of the clinical outcome.

Kitab, Bouchra; Essaid El Feydi, Abdellah; Afifi, Rajaa; Trepo, Christian; Benazzouz, Mustapha; Essamri, Wafaa; Zoulim, Fabien; Chemin, Isabelle; Alj, Hanane Salih; Ezzikouri, Sayeh; Benjelloun, Soumaya

2012-01-01

177

People with Multiple Tattoos and/or Piercings Are Not at Increased Risk for HBV or HCV in The Netherlands  

PubMed Central

Background Although published results are inconsistent, it has been suggested that tattooing and piercing are risk factors for HBV and HCV infections. To examine whether tattooing and piercing do indeed increase the risk of infection, we conducted a study among people with multiple tattoos and/or piercings in the Netherlands who acquired their tattoos and piercings in the Netherlands and/or abroad. Methods Tattoo artists, piercers, and people with multiple tattoos and/or piercings were recruited at tattoo conventions, shops (N?=?182), and a biannual survey at our STI-outpatient clinic (N?=?252) in Amsterdam. Participants were interviewed and tested for anti-HBc and anti-HCV. Determinants of HBV and HCV infections were analysed using logistic regression analysis. Results The median number of tattoos and piercings was 5 (IQR 2–10) and 2 (IQR 2–4), respectively. Almost 40% acquired their tattoo of piercing abroad. In total, 18/434 (4.2%, 95%CI: 2.64%–6.46%) participants were anti-HBc positive and 1 was anti-HCV positive (0.2%, 95%CI: 0.01%–1.29%). Being anti-HBc positive was independently associated with older age (OR 1.68, 95%CI: 1.03–2.75 per 10 years older) and being born in an HBV-endemic country (OR 7.39, 95%CI: 2.77–19.7). Tattoo- and/or piercing-related variables, like having a tattoo or piercing in an HBV endemic country, surface percentage tattooed, number of tattoos and piercings etc., were not associated with either HBV or HCV. Conclusions We found no evidence for an increased HBV/HCV seroprevalence among persons with multiple tattoos and/or piercings, which might be due to the introduction of hygiene guidelines for tattoo and piercing shops in combination with the low observed prevalence of HBV/HCV in the general population. Tattoos and/or piercings, therefore, should not be considered risk factors for HBV/HCV in the Dutch population. These findings imply the importance of implementation of hygiene guidelines in other countries.

Urbanus, Anouk T.; van den Hoek, Anneke; Boonstra, Albert; van Houdt, Robin; de Bruijn, Lotte J.; Heijman, Titia; Coutinho, Roel A.; Prins, Maria

2011-01-01

178

Comparative evaluation of a triplex nucleic acid test for detection of HBV DNA, HCV RNA, and HIV-1 RNA, with the Procleix Tigris System.  

PubMed

Nucleic acid testing (NAT) is valuable for screening blood donors for occult hepatitis B virus (HBV) infection and infection during the window period in countries where HBV is endemic, such as China. An "in-house" NAT (Triplex NAT) was developed for screening for HBV DNA, hepatitis C virus (HCV) RNA, and the human immunodeficiency virus type 1 (HIV-1) RNA. Using the Triplex NAT, a head-to-head comparative clinical evaluation was carried out against the most common commercial NAT used for blood screening in China: the Procleix Tigris System. A total of 33,025 specimens which were negative for Hepatitis B surface antigen, HCV antibody and HIV-1 antibody/antigen from potential blood donors were tested for HBV DNA, HCV RNA, and HIV-1 RNA by both the in-house Triplex assay and the commercially available Procleix Tigris System. Eleven specimens were detected as HBV positive by both NATs. Twelve specimens were detected as HBV positive by the Procleix Ultrio assay and the discriminatory assays, and not the Triplex. Twenty-eight specimens were detected as HBV positive by the Triplex and not the Procleix Ultrio. This study, combined with other data obtained in China, suggest that at least 50% HBV surface antigen negative but DNA-positive blood donations would be undetected using the current commercial NATs because of their insufficient sensitivity and/or Mini-Pool formatting strategies. PMID:23142222

Xiao, Xinglong; Zhai, Jianxin; Zeng, Jinfeng; Tian, Cong; Wu, Hui; Yu, Yigang

2013-02-01

179

Pro-sociality without empathy  

PubMed Central

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.

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

2012-01-01

180

Subfulminant hepatitis B after infliximab in Crohn's disease: Need for HBV-screening?  

PubMed Central

Infections are a major adverse effect during the treatment with anti-TNF-?. While exclusion of any bacterial infection and screening for tuberculosis are mandatory before initiating a therapy with anti-TNF- ?-antibodies, there are no guidelines whether to screen for or how to deal with chronic viral infections such as hepatitis B. In this case report, we have described a patient with Crohn's disease who developed subfulminant hepatitis B after the fourth infusion of infliximab due to an unrecognized HBs-antigen carrier state. He recovered completely after lamivudine therapy was started, but this severe adverse event could have been prevented if screening for HBV and pre-emptive therapy with lamivudine would have been started prior to infliximab. We therefore strongly argue in favor of extended screening recommendations for infectious diseases including viral infections before considering a therapy with infliximab.

Millonig, Gunda; Kern, Michaela; Ludwiczek, Othmar; Nachbaur, Karin; Vogel, Wolfgang

2006-01-01

181

The role of HBsAg levels in the current management of chronic HBV infection  

PubMed Central

Chronic hepatitis B virus (HBV) infection can result in liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). However, the natural course of the disease is highly dynamic and not every patient requires therapy. The challenges for optimal management are who to treat, which therapeutic regimen to use, and when to begin or stop treatment. Constant monitoring is mandatory to predict the natural course and guide treatment decisions. Surrogate markers for baseline and on treatment decisions are needed. Besides HBV DNA, hepatitis B surface antigen levels also proved to be useful to help judge the natural course and guide treatment. High levels of HBsAg are suggestive of low fibrosis and immune tolerance in hepatitis B e antigen (HBeAg) positive patients; whereas low levels of HBsAg indicate a lower risk for HCC and inactive carrier state in HBeAg negative patients. Data also support the possible use of HBsAg levels as an on-treatment response marker. So far, the best evidence exists for treatment with interferon (IFN)-? where lack of HBsAg decline after 12 weeks is associated with non-response. Thus, stopping rules after 12 weeks therapy could be established for HBeAg positive as well as for HBeAg negative patients. However, the positive predictive value for achieving sustained response is still vague. The value of HBsAg monitoring is less clear during treatment with nucleos(t)ide analogues (NA) but it can be a useful marker for new concepts such as stopping NA or add-on IFN strategies. Currently, several studies are underway to validate HBsAg in these settings.

Honer zu Siederdissen, Christoph; Cornberg, Markus

2014-01-01

182

Prevalence of GBV-C among Iranian HBV positive patients using PCR-RFLP technique  

PubMed Central

Aim The aim of this study was to investigate the prevalence of GBV-C among Iranian HBV positive patients using PCR-RFLP technique. Background GBV-C was a member of flaviviridae family and recently propose to classify as members of a fourth genus in this family, named Pegivirus and suggest that at least one quarter of the world's population has been infected with this virus. GBV-C can be transmitted via the blood-borne route, although vertical and sexual transmission is very well documented. Patients and methods 100 serum samples were collected from HBsAg positive patients in 2011–2012. RNA was extracted with Qiagene mini kit. cDNA was synthesized by Reverse Transcriptase method and amplified by Semi- nested PCR method. After designing specific primers, the semi nested PCR was optimized, then sequences of PCR products were analyzed with software such as neb cutter, and sites of restriction enzymes were determined and suitable enzymes were selected for RFLP (Restriction Fragment Length Polymorphism). Results PCR products were analyzed in 2% agarose gels containing ethidium bromide and were visualized with ultraviolet (UV) light. A 230 bp band was observed in comparison with 100 kb ladder; this band indicates our target gene of GBV-C genome have been isolate from serum samples. Conclusion It seems that Co-infection of GBV-C and HBV are common and This method had acceptable sensitivity for detecting GBV-C and determining its genotype, and more affordable than the other techniques; so the results of this study showed the prevalence of GBV-C were 12 serums of 100 serums HBsAg positive in goal population and one sample from 12 GBV-C positive serums was genotype 3 and the others were genotype 2.

Yazdani, Laleh; Khanlari, Zahra; Dawood Mousavi Nasab, Seyed; Ali Ahmadi, Nayeb; Imanzad, Masoumeh

2013-01-01

183

Runoff simulation in the Ferghana Valley (Central Asia) using conceptual hydrological HBV-light model  

NASA Astrophysics Data System (ADS)

Glaciers and permafrost on the ranges of the Tien Shan mountain system are primary sources of water in the Ferghana Valley. The water artery of the valley is the Syr Darya River that is formed by confluence of the Naryn and Kara Darya rivers, which originate from the mountain glaciers of the Ak-Shyrak and the Ferghana ranges accordingly. The Ferghana Valley is densely populated and main activity of population is agriculture that heavily depends on irrigation especially in such arid region. The runoff reduction is projected in future due to global temperature rise and glacier shrinkage as a consequence. Therefore, it is essential to study climate change impact on water resources in the area both for ecological and economic aspects. The evaluation of comparative contribution of small upper catchments (n=24) with precipitation predominance in discharge and the large Naryn and Karadarya River basins, which are fed by glacial melt water, to the Fergana Valley water balance under current and future climatic conditions is general aim of the study. Appropriate understanding of the hydrological cycle under current climatic conditions is significant for prognosis of water resource availability in the future. Thus, conceptual hydrological HBV-light model was used for analysing of the water balance of the small upper catchments that surround the Ferghana Valley. Three trial catchments (the Kugart River basin, 1010 km²; the Kurshab River basin, 2010 km2; the Akbura River basin, 2260 km²) with relatively good temporal quality data were chosen to setup the model. Due to limitation of daily temperature data the MODAWEC weather generator, which converts monthly temperature data into daily based on correlation with rainfall, was tested and applied for the HBV-light model.

Radchenko, Iuliia; Breuer, Lutz; Forkutsa, Irina; Frede, Hans-Georg

2013-04-01

184

Attempted therapeutic immunization in a chimpanzee chronic HBV carrier with a high viral load  

PubMed Central

Background We previously reported successful therapeutic immunization in a chimpanzee having a relatively low viral load, which was immunized with recombinant plasmid hepatitis B surface antigen (HBsAg) DNA and boosted with recombinant HBsAg encoding canarypox virus. In the present study, we attempted to confirm these findings in an animal with a high virus load. Methods and Results We tested three immunization strategies successively over a 3-year period. In the first of these, we administered four monthly injections of DNA encoding HBsAg + PreS2 + hepatitis B core antigen (HBcAg) + DNA encoding interleukin (IL)-12, (given 3 days later), and boosted with canarypox expressing all of the above HBV genes 6 months after initial immunization. No reduction in viral load was observed. In the second trial, we administered lamivudine for 8 weeks, and then began monthly DNA-based immunization with plasmids expressing the above viral genes; however, viral loads rebounded 1 week after termination of lamivudine therapy. In a third trial, we continued lamivudine therapy for 30 weeks and immunized with vaccinia virus expressing the above viral genes 18 and 23 weeks after the start of lamivudine therapy. Again viral loads rebounded shortly after cessation of lamivudine treatment. Analysis of cell-mediated immune responses, and their avidity, revealed that DNA-based immunization produced the strongest enhancement of high avidity T-cell responses, while recombinant vaccinia immunization during lamivudine therapy enhanced low avidity responses only. The strongest low and high avidity responses were directed to the middle surface antigen. Conclusions Three strategies for therapeutic immunization failed to control HBV viremia in a chronically infected chimpanzee with a high viral load.

Shata, Mohamed Tarek M.; Pfahler, Wolfram; Brotman, Betsy; Lee, Dong-Hun; Tricoche, Nancy; Murthy, Krishna; Prince, Alfred M.

2006-01-01

185

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

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.

2014-01-01

186

Is Universal HBV Vaccination of Healthcare Workers a Relevant Strategy in Developing Endemic Countries? The Case of a University Hospital in Niger  

PubMed Central

Background Exposure to hepatitis B virus (HBV) remains a serious risk to healthcare workers (HCWs) in endemic developing countries owing to the strong prevalence of HBV in the general and hospital populations, and to the high rate of occupational blood exposure. Routine HBV vaccination programs targeted to high-risk groups and especially to HCWs are generally considered as a key element of prevention strategies. However, the high rate of natural immunization among adults in such countries where most infections occur perinatally or during early childhood must be taken into account. Methodology/Principal Findings We conducted a cross sectional study in 207 personnel of 4 occupational groups (medical, paramedical, cleaning staff, and administrative) in Niamey’s National Hospital, Niger, in order to assess the prevalence of HBV markers, to evaluate susceptibility to HBV infection, and to identify personnel who might benefit from vaccination. The proportion of those who declared a history of occupational blood exposure ranged from 18.9% in the administrative staff to 46.9% in paramedical staff. Only 7.2% had a history of vaccination against HBV with at least 3 injections. Ninety two percent were anti-HBc positive. When we focused on170 HCWs, only 12 (7.1%) showed no biological HBV contact. Twenty six were HBsAg positive (15,3%; 95% confidence interval: 9.9%–20.7%) of whom 8 (32%) had a viral load >2000 IU/ml. Conclusions/Significance The very small proportion of HCWs susceptible to HBV infection in our study and other studies suggests that in a global approach to prevent occupational infection by bloodborne pathogens, a universal hepatitis B vaccination of HCWs is not priority in these settings. The greatest impact on the risk will most likely be achieved by focusing efforts on primary prevention strategies to reduce occupational blood exposure. HBV screening in HCWs and treatment of those with chronic HBV infection should be however considered.

Pellissier, Gerard; Yazdanpanah, Yazdan; Adehossi, Eric; Tosini, William; Madougou, Boubacar; Ibrahima, Kaza; Lolom, Isabelle; Legac, Sylvie; Rouveix, Elisabeth; Champenois, Karen; Rabaud, Christian; Bouvet, Elisabeth

2012-01-01

187

A Novel Inhibitor of Human La Protein with Anti-HBV Activity Discovered by Structure-Based Virtual Screening and In Vitro Evaluation  

PubMed Central

Background Over 350 million people worldwide are infected with hepatitis B virus (HBV), a major cause of liver failure and hepatocellular carcinoma. Current therapeutic agents are highly effective, but are also associated with development of viral resistance. Therefore, strategies for identifying other anti-HBV agents with specific, but distinctive mechanisms of action are needed. The human La (hLa) protein, which forms a stabilizing complex with HBV RNA ribonucleoprotein to promote HBV replication, is a promising target of molecular therapy. Aims This study aimed to discover novel inhibitors of hLa that could inhibit HBV replication and expression. Methods A multistage molecular docking approach was used to screen a Specs database and an in-house library against hLa binding sites. Sequential in vitro evaluations were performed to detect potential compounds with high scores in HepG2.2.15 cells. Results Of the 26 potential compounds with high scores chosen for experimental verification, 12 had HBV DNA inhibition ratios of less than 50% with P<0.05. Six had significant inhibition of HBV e antigen (HBeAg) levels, and 13 had significant inhibition of HBV surface antigen (HBsAg) levels by in vitro assays. Compounds HBSC-11, HBSC-15 and HBSC-34 (HBSC is system prefix for active compounds screened by the library) were selected for evaluation. HBSC-11 was found to have an obvious inhibitory effect on hLa transcription and expression. Conclusions Our findings suggest that anti-HBV activity of HBSC-11 may be mediated by a reduction in hLa levels. In addition, our data suggest the potential clinical use of hLa inhibitors, such as HBSC-11, for treating HBV infection.

Tang, Jing; Huang, Zhi-Min; Chen, Ying-Yi; Zhang, Zhao-Hui; Liu, Gao-Lin; Zhang, Jian

2012-01-01

188

Immune Exhaustion and Immune Senescence - Two Distinct Pathways for HBV Vaccine Failure during HCV and/or HIV Infection  

PubMed Central

Given the shared risk factors for transmission, co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) is quite common, and may lead to increases in morbidity and mortality. As such, HBV vaccine is recommended as the primary means to prevent HBV super-infection in HCV- and/or HIV-infected individuals. However, vaccine response (sero-conversion with a hepatitis B surface antibody titer >10 IU/L) in this setting is often blunted, with poor response rates to standard HBV vaccinations in virally infected individuals when compared to the healthy subjects. This phenomenon also occurs to other vaccines in adults, such as pneumococcal and influenza vaccines, in other immunocompromised hosts who are really at risk for opportunistic infections, such as individuals with hemodialysis, transplant, and malignancy. In this review, we summarize the underlying mechanisms involving vaccine failure in these conditions, focusing on immune exhaustion and immune senescence - two distinct signaling pathways regulating cell function and fate. We raise the possibility that blocking these negative signaling pathways might improve success rates of immunizations in the setting of chronic viral infection.

Yao, Zhi Q.; Moorman, Jonathan P.

2013-01-01

189

Effect and mechanisms of curdlan sulfate on inhibiting HBV infection and acting as an HB vaccine adjuvant.  

PubMed

In this study, the effect and mechanisms of curdlan sulfate (CS3) on hepatitis B virus (HBV) infection and promoting immune response of the mice immunized with recombinant hepatitis B surface protein (HBsAg) were investigated. The results showed that CS3 could inhibit HBV infection of HepG2 and HepaRG cells, especially the process of HBV particle binding to the cell surfaces. The surface plasmon response (SPR) technology indicated that CS3 could bind with recombinant HBsAg and the binding ability depended on the content of sulfate groups on the polysaccharide chains. Co-administration of CS3 to BALB/c mice immunized with HBsAg significantly enhanced the influx of macrophages and dendritic cells in spleen, increased antigen-specific CD4(+) and CD8(+) cell numbers, and promoted splenocyte proliferation. The titer of HBsAg-specific antibodies was also augmented by use of CS3 as a vaccine adjuvant. The higher expression of interferon (IFN)-?, lower expression of interleukin (IL)-4, and higher IgG2a/IgG1 ratio within the anti-HBsAg antibodies in mice immunized with HBsAg plus CS3 than those in mice receiving HBsAg alone indicated that CS3 induced a shift toward a Th1-biased immune response. These results presented that CS3 could be developed as an immunotherapy agent or vaccine adjuvant for HBV infection treatment or prevention. PMID:24906778

Li, Pingli; Tan, Haining; Xu, Dongqing; Yin, Fengxin; Cheng, Yanna; Zhang, Xinke; Liu, Yuhong; Wang, Fengshan

2014-09-22

190

Sequence Conservation of the Region Targeted by the Abbott RealTime HBV Viral Load Assay in Clinical Specimens  

PubMed Central

The Abbott RealTime HBV assay targets the N-terminal region of the S gene. Here we analyzed the sequence variability of the assay target region from >2,100 clinical specimens. Thermodynamic modeling of the percentage of bound primer/probe at the assay annealing temperature was performed to assess the potential effect of sequence variability.

Rhoads, James; Young, Thomas P.; Parkin, Neil T.; Holzmayer, Vera; Yuen, Lilly; Mullen, Carolyn

2013-01-01

191

Sequence conservation of the region targeted by the Abbott RealTime HBV viral load assay in clinical specimens.  

PubMed

The Abbott RealTime HBV assay targets the N-terminal region of the S gene. Here we analyzed the sequence variability of the assay target region from >2,100 clinical specimens. Thermodynamic modeling of the percentage of bound primer/probe at the assay annealing temperature was performed to assess the potential effect of sequence variability. PMID:23345287

Cloherty, Gavin A; Rhoads, James; Young, Thomas P; Parkin, Neil T; Holzmayer, Vera; Yuen, Lilly; Mullen, Carolyn

2013-04-01

192

Simultaneous screening for HBV DNA and HCV RNA genomes in blood donations using a novel TaqMan PCR assay  

Microsoft Academic Search

The risk of contracting hepatitis from blood transfusions is estimated to be 1 in 63?000 in the case of hepatitis B virus (HBV) and 1 in 103?000 in the case of hepatitis C virus (HCV). In some countries (Germany, USA and England, for example), molecular protocols are evaluated to detect viral genomes in blood donations in order to reduce the

Bernard Mercier; Laetitia Burlot; Claude Férec

1999-01-01

193

Characterization of the anti-HBV activity of HLP1-23, a human lactoferrin-derived peptide.  

PubMed

Lactoferrin (Lf) was shown to exhibit its antiviral activity at an early phase of viral infection and a mechanism whereby the protein interacts with host cell surface molecules has been suggested. In this study, human Lf (HLf) and seven HLf-derived synthetic peptides (HLP) corresponding to the N-terminal domain of the native protein (1-47 amino acids sequence) were assayed for their capacity to prevent hepatitis B virus (HBV) infection and replication using the HepaRG and HepG2.2.2.15 cell lines. Of the series tested, four peptides showed 40-75% inhibition of HBV infection in HepaRG cells, HLP1-23 , containing the GRRRR cationic cluster, being the most potent. Interestingly, this cluster is one of the two glycosaminoglycan binding sites of the native HLf involved in its antiviral activity; however, the mechanism of the HLP1-23 action was different from that of the full-length protein, the peptide inhibiting HBV infection when pre-incubated with the virus, while no effect was observed on the target cells. It is suggested that the cationic cluster is sufficient for the peptide to interact stably with negatively charged residues on the virion envelope, while the absence of the second glycosaminoglycan binding site prevents its efficient attachment to the cells. In conclusion, this peptide may constitute a non-toxic approach for potential clinical applications in inhibiting HBV entry by neutralizing the viral particles. PMID:23508903

Florian, Paula E; Macovei, Alina; Lazar, Catalin; Milac, Adina L; Sokolowska, Izabela; Darie, Costel C; Evans, Robert W; Roseanu, Anca; Branza-Nichita, Norica

2013-05-01

194

Factors Associated with Elevated ALT in an International HIV/HBV Co-Infected Cohort on Long-Term HAART  

PubMed Central

Background Previous studies have demonstrated that hepatitis B virus (HBV) infection increases the risk for ALT elevations in HIV-HBV co-infected patients during the first year of HAART; however, there is limited data on the prevalence of ALT elevations with prolonged HAART in this patient group. Methods/Principal findings To identify factors associated with ALT elevations in an HIV-HBV co-infected cohort receiving prolonged HAART, data from 143 co-infected patients on HAART enrolled in an international HIV-HBV co-infected cohort where ALT measurements were obtained every 6 months was analysed. A person-visit analysis was used to determine frequency of ALT elevation (?2.5×ULN) at each visit. Factors associated with ALT elevation were determined using multivariate logistic regression with generalized estimating equations to account for correlated data. The median time on HAART at the end of follow-up was 5.6 years (range 0.4–13.3) years. During follow-up, median ALT was 36 U/L with 10.6% of person-visits classified as having ALT elevation. Most ALT elevations were grade 2 (86.5%), with only 13.5% of all ALT elevations grade 3 or higher. Univariate associations with ALT elevation (p<0.05) included history of AIDS, HBV DNA ?2,000 IU/ml, HBeAg positive, study visit CD4 <200 cells/ml and nadir CD4 <200 cells/ml. In the multivariate analysis, only study visit CD4 <200 cells/ml (OR 2.07, 95%CI 1.04–4.11, p?=?0.04) and HBeAg positive status (OR 2.22, 95%CI 1.03–4.79, p?=?0.04) were independently associated with ALT elevation. Conclusions In this HIV-HBV co-infected cohort, elevated ALT after >1 year of HAART was uncommon, and severe ALT elevations were rare. HIV-HBV co-infected patients on long-term HAART who are either HBeAg positive or have a CD4 count of <200 cells/ml are at increased risk for ALT elevations.

Audsley, Jennifer; Seaberg, Eric C.; Sasadeusz, Joe; Matthews, Gail V.; Avihingsanon, Anchalee; Ruxrungtham, Kiat; Fairley, Kit; Finlayson, Robert; Hwang, Hyon S.; Littlejohn, Margaret; Locarnini, Stephen; Dore, Gregory J.; Thio, Chloe L.; Lewin, Sharon R.

2011-01-01

195

Hyperimmune anti-HBs plasma as alternative to commercial immunoglobulins for prevention of HBV recurrence after liver transplantation  

PubMed Central

Background Hepatitis B immune globulins (HBIG) in combination with nucleos(t)ide analogues (NA) are effectively used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, associated treatment costs for HBIG are exceedingly high. Methods Fresh frozen plasma obtained from blood donors with high anti-HBs levels (hyperimmune plasma, HIP) containing at least 4,500 IU anti-HBs was used as alternative treatment for HBV recurrence prophylaxis post-LT. Results Twenty-one HBV-related LT recipients received HIP starting at transplantation, followed by long-term combination treatment with NA. Mean follow-up time was 4.5 years (range 0.5-12.6) and each patient received on average 8.2 HIP per year (range 5.8-11.4). Anti-HBs terminal elimination kinetic after HIP administration was 20.6 days (range 13.8-30.9), which is comparable to values reported for commercial HBIG products. All 21 patients remained free of HBV recurrence during follow-up and no transfusion-transmitted infection or other serious complication was observed. Seven patients developed reversible mild transfusion reactions. The cost for one HIP unit was US$140; average yearly HBIG treatment cost was US$1,148 per patient, as compared to US$25,000-100,000 for treatment with commercial HBIG. Conclusion The results of this study suggest that the use of HIP may be a useful and economical approach for the prevention of HBV recurrence post-LT if used in combination with NA. Additional prospective controlled studies in larger populations are needed to confirm these results.

2010-01-01

196

Intestinal microbiota was assessed in cirrhotic patients with hepatitis B virus infection. Intestinal microbiota of HBV cirrhotic patients.  

PubMed

To unravel the profile of intestinal microecological parameters in Chinese patients with asymptomatic carriage of hepatitis B virus (HBV), chronic hepatitis B, decompensated HBV cirrhosis, and health controls and to establish their correlation with liver disease progression, we performed quantitative PCR and immunological techniques to investigate fecal parameters, including population of fecal predominant bacteria and the abundance of some virulence genes derived from Escherichia coli, Bacteroides fragilis, Clostridium difficile, and Clostridium perfringens in fecal crude DNA and some immunological parameters in extracts of all fecal samples. Data analysis indicated that 16S rRNA gene copy numbers for Faecalibacterium prausnitzii, Enterococcus faecalis, Enterobacteriaceae, bifidobacteria, and lactic acid bacteria (Lactobacillus, Pediococcus, Leuconostoc, and Weissella) showed marked variation in the intestine of HBV cirrhotic patients. The Bifidobacteria/Enterobacteriaceae (B/E) ratio, which may indicate microbial colonization resistance of the bowel, was decreased significantly in turn from 1.15?±?0.11 in healthy controls, 0.99?±?0.09 in asymptomatic carriers, and 0.76?±?0.08 in patients with chronic hepatitis B to 0.64?±?0.09 in patients with decompensated HBV cirrhosis (for all, P?HBV cirrhotic patients were present at higher levels than in other groups, which indicates that a complicated autoregulatory system tries to achieve a new intestinal microecological balance. PMID:21286703

Lu, Haifeng; Wu, Zhongwen; Xu, Wei; Yang, Jiezuan; Chen, Yunbo; Li, Lanjuan

2011-04-01

197

Role of the line probe assay INNO-LiPA HBV DR and ultradeep pyrosequencing in detecting resistance mutations to nucleoside/nucleotide analogues in viral samples isolated from chronic hepatitis B patients.  

PubMed

Despite the effectiveness of nucleoside/nucleotide analogues in the treatment of chronic hepatitis B (CHB), their long-term administration is associated with the emergence of resistant hepatitis B virus (HBV) mutants. In this study, mutations resulting in antiviral resistance in HBV DNA samples isolated from 23 CHB patients (nine treatment naïve and 14 treated previously) were studied using a line probe assay (INNO-LiPA HBV DR; Innogenetics) and ultradeep pyrosequencing (UDPS) methods. Whilst the INNO-LiPA HBV DR showed no resistance mutations in HBV DNA samples from treatment-naive patients, mutations mediating lamivudine resistance were detected in three samples by UDPS. Among patients who were treated previously, 19 mutations were detected in eight samples using the INNO-LiPA HBV DR and 29 mutations were detected in 12 samples using UDPS. All mutations detected by the INNO-LiPA HBV DR were also detected by UDPS. There were no mutations that could be detected by INNO-LiPA HBV DR but not by UDPS. A total of ten mutations were detected by UDPS but not by INNO-LiPA HBV DR, and the mean frequency of these mutations was 14.7?%. It was concluded that, although INNO-LiPA HBV DR is a sensitive and practical method commonly used for the detection of resistance mutations in HBV infection, UDPS may significantly increase the detection rate of genotypic resistance in HBV at an early stage. PMID:24045109

Mese, Sevim; Arikan, Muzaffer; Cakiris, Aris; Abaci, Neslihan; Gumus, Ergun; Kursun, Olcay; Onel, Derya; Ustek, Duran; Kaymakoglu, Sabahattin; Badur, Selim; Yenen, Osman Sadi; Bozkaya, Emel

2013-12-01

198

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

PubMed

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

Wang, Yang; Lu, Zhiqiang; Jiang, Haobo

2014-07-01

199

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

PubMed Central

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.

Wang, Yang; Lu, Zhiqiang; Jiang, Haobo

2014-01-01

200

Collective Protection (ColPro) Field Testing.  

National Technical Information Service (NTIS)

This Test Operations Procedure (TOP) provides the standard process for preparation, planning, conduct, and reporting for field testing of collective protection (ColPro) systems. This process is designed to evaluate the effectiveness of mobile and stationa...

2011-01-01

201

BudPro — Budget Projection Software  

Microsoft Academic Search

Agricultural producers need to develop marketing plans. A major component of a marketing plan is an estimate of the price necessary to cover all costs based on expected yields (break-even price). BudPro is designed to help agricultural produc- ers with this estimation. The BudPro for Windows software includes one program for all crops and one for stocker cattle. The software

Stan Bevers; Jackie Smith; David Rempe

202

NT-pro BNP e angina instabile  

Microsoft Academic Search

Summary Nt-pro BNP in unstable coronary artery disease. Introduction. The natriuretic peptides and, more recently, the N-terminal fragment of Brain Natriuretic Peptide (NT- proBNP) caused great interest both in monitoring cardiac insufficiency and in the risk stratification in acute coronary disease. Anyway, the knowledge of the mechanism of natriuretic peptides synthesis, release and regulation is still incomplete. Besides myocardial necrosis

M. Lotzniker; N. Covini; G. Re; S. Finazzi; C. Inserra; R. Pacifici; P. G. Zuccaro

203

Technology evaluation: PRO-542, Progenics Pharmaceuticals inc.  

PubMed

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

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

2000-12-01

204

Optimisation of Prime-Boost Immunization in Mice Using Novel Protein-Based and Recombinant Vaccinia (Tiantan)-Based HBV Vaccine  

PubMed Central

Background A therapeutic vaccine for chronic hepatitis B virus (HBV) infection that enhances virus-specific cellular immune responses is urgently needed. The “prime–boost” regimen is a widely used vaccine strategy against many persistence infections. However, few reports have addressed this strategy applying for HBV therapeutic vaccine development. Methodology/Principal Findings To develop an effective HBV therapeutic vaccine, we constructed a recombinant vaccinia virus (Tiantan) containing the S+PreS1 fusion antigen (RVJSS1) combined with the HBV particle-like subunit vaccine HBVSS1 to explore the most effective prime–boost regimen against HBV. The immune responses to different prime–boost regimens were assessed in C57BL/C mice by ELISA, ELISpot assay and Intracellular cytokine staining analysis. Among the combinations tested, an HBV protein particle vaccine priming and recombinant vaccinia virus boosting strategy accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody) titres as well as the strongest multi-antigen (PreS1, and S)-specific cellular immune response. HBSS1 protein prime/RVJSS1 boost immunization was also generated more significant level of both CD4+ and CD8+ T cell responses for Th1 cytokines (TNF-? and IFN-?). Conclusions The HBSS1 protein-vaccine prime plus RVJSS1 vector boost elicits specific antibody as well as CD4 and CD8 cells secreting Th1-like cytokines, and these immune responses may be important parameters for the future HBV therapeutic vaccines.

Deng, Yao; Wen, Bo; Wang, Wen; Xiong, Shaoqing; Ruan, Li; Tan, Wenjie

2012-01-01

205

Screening differential expression of serum proteins in AFP-negative HBV-related hepatocellular carcinoma using iTRAQ -MALDI-MS/MS.  

PubMed

Hepatocellular carcinoma(HCC) is serious condition associated with a high morbidity and mortality. Therefore is an urgent need to develop novel noninvasive techniques for early diagnosis, particularly for patients with AFP-negative [AFP(-)] HCC. In this study, iTRAQ-MALDI-MS/MS was used to identify differentially expressed proteins in AFP(-) HBV-related HCC compared with non-cancerous hepatitis B virus (HBV) and healthy controls subjects.Serum was obtained from 18 patients with AFP(-) HBV-related HCC, 18 matched patients with HBV without HCC and 18 healthy control subjects. High abundance proteins were removed from serum and the differentially expressed proteins from the three groups were screened out using iTRAQ-MALDI-MS/MS. The Gene Ontology (GO) function and the interaction networks of differentially expressed proteins were then analyzed. A total of 24 expressed differential proteins associated with AFP(-) HBV-related HCC were screened out, 15 proteins were up-regulated and 9 down-regulated. The most common molecular function of the 24 differentially expressed proteins was enzyme inhibition. Interaction network of the 24 differentially expressed proteins showed that 14 proteins (C5, KNG1, FN1, LRG1, HRG, SERPINC1, CRP, APOB, SAA1, APCS, C4BPA, CFI, CFB and GSN) were central to the functional network. The expression levels of the GSN protein were down-regulated in AFP(-) HBV-related HCC subjects compared with healthy controls and the HBV group (p<0.01), consistent with the iTRAQ results.The 14 proteins from the serum of AFP(-) HBV-related HCC appeared at the fulcrum of the functional network and were differentially expressed compare to HBV and healthy controls suggesting a possible association with HCC progression. PMID:24195504

He, X; Wang, Y; Zhang, W; Li, H; Luo, R; Zhou, Y; Liao, C Li M; Huang, H; Lv, X; Xie, Z; He, M

2014-01-01

206

CTL escape mutations of core protein are more frequent in strains of HBeAg negative patients with low levels of HBV DNA  

PubMed Central

Background Recent studies have suggested that Cytotoxic T lymphocytes (CTL) play a key role in eliminating hepatitis B virus (HBV). Objectives We aimed to investigate the role of mutations in different immune epitopes of hepatitis B core antigen (HBcAg) among Iranians with HBeAg negative chronic hepatitis B (e-CHB), and asymptomatic carriers (ASCs). Study design Amino acids 1-150 of HBcAg were characterized for HBV strains from 29 e-CHB patients and 48 ASCs from Iran. All patients were infected with HBV genotype D and had previously been investigated for the presence of pre-core and basic core promoter (BCP) mutants. Results Amino acid mutations of core protein were observed more frequently in HBV strains from ASCs than e-CHB patients (p=0.014). Asn67 mutation was mutually exclusive to the combination Ile66 and Ser69 (P<0.001). Substitutions for Ser21 and Thr12Ser were associated with lower serum levels of HBV DNA (p<0.001). None of the patients with mutations in HLA-A2 CTL epitope, 18-27, had serum HBV DNA more than 105 copies/mL (p<0.001). By multivariate analysis, high level (> 105 copies/mL) of serum HBV DNA was inversely associated with the presence of mutations in CTL epitopes of HBc (OR:0.11 , p=0.015), while it was directly associated with presence of promoter double T1762A1764 mutations together with G1757 (OR:16.87, p=0.004) Conclusion The inverse correlation between serum levels of HBV DNA and CTL escape mutations of the core protein in HBeAg seroconverted patients, supports the notion that selection of CTL escape mutations consolidates the persistence of HBV infection despite reducing viral fitness.

Sendi, Hossein; Mehrab-Mohseni, Marjan; Shahraz, Saeid; Norder, Helene; Alavian, Seyed-Moayed; Noorinayer, Babak; Zali, Mohammad R.; Pumpens, Paul; Bonkovsky, Herbert L.; Magnius, Lars O.

2009-01-01

207

A new DTPw-HBV/Hib vaccine: immune memory after primary vaccination and booster dosing in the second year of life.  

PubMed

The response to booster vaccination at 15-18 months of age and the presence of immune memory in 10-month old children, primed with a new combined diphtheria-tetanus-hepatitis B-whole cell pertussis vaccine extemporaneously mixed with Haemophilus influenzae type b-tetanus toxoid conjugate (DTPw-HBV/Hib) from new antigen sources and containing 2.5 microg polyribosyl-ribitol-phosphate (PRP) was assessed. Primary vaccination with the new DTPw-HBV/Hib vaccine was immunogenic and of comparable tolerability to commercially available Tritanrix HepB/Hiberix. Children were boosted with DTPw-HBV, DTPw-HBV/Hib or separate DTPw-HBV+Hiberix. Immune memory was assessed through administration of 10 microg PRP polysaccharide. Anti-PRP antibody GMCs increased substantially after the challenge in DTPw-HBV/Hib-primed subjects indicating the presence of immune memory. One month after the booster dose, 100% of subjects had seroprotective antibody concentrations against PRP, diphtheria and tetanus, >95% were seroprotected against hepatitis B, > or =94.0% had a pertussis booster response. Substantial increases in antibody GMCs against all antigens were observed. Swelling >20 mm was the most common Grade 3 solicited symptom reported (up to 26.0% of subjects). Fever >39.5 degrees C was uncommon (>2.5%). Eleven large swelling reactions were reported; none involved an adjacent joint. One serious adverse event occurred that was considered unrelated to vaccination. This new DTPw-HBV/Hib vaccine with new vaccine components and 2.5 microg PRP induced effective priming against Hib evidenced by a vigorous anamnestic response on exposure to PRP polysaccharide. The booster dose was immunogenic and the safety profile was acceptable. Combined DTPw-HBV and DTPw-HBV/Hib vaccines using new vaccine antigen sources will promote continued supply of combined DTPw-based vaccines to global mass vaccination campaigns. PMID:18376148

Gatchalian, Salvacion; Reyes, Marietta; Bermal, Nancy; Chandrasekaran, Vijayalakshmi; Han, Htay Htay; Bock, Hans L; Lefevre, Inge

2008-01-01

208

Towards the complete eradication of mother-to-child HIV/HBV coinfection at Saint Camille Medical Centre in Burkina Faso, Africa.  

PubMed

The coinfection of HIV and hepatitis B virus (HBV) and their vertical transmission constitute a public health problem in sub-Saharan countries of Africa. The objectives of this research are: i) identify the pregnant women that are coinfected by HIV and HBV at Saint Camille Medical Centre; ii) use three antiretroviral drugs (zidovudine, nevirapine and lamivudine) to interrupt the vertical transmission of HIV and HBV from infected mothers; and iii) use the PCR technique to diagnose children who are vertically infected by these viruses in order to offer them an early medical assistance. At Saint Camille Medical Centre, 115 pregnant women, aged from 19 to 41 years, were diagnosed as HIV-positive and, among them, 14 coinfected with HBV. They had at least 32 weeks of amenorrhoea and all of them received the HAART, which contained lamivudine. Two to six months after childbirth, the babies underwent PCR diagnosis for HIV and HBV. The results revealed that, among these mothers, 64.4% were housewives, 36.5% were illiterates, and only 1.7% had a university degree. The rate of vertical transmission of HIV and HBV was 0.0% (0/115) and 21.4% (3/14), respectively. The 3 mothers who transmitted the HBV to their children had all HBsAg, HbeAg, and HBV DNA positive. An antiretroviral therapy that in addition to zidovudine and nevirapine includes lamivudine could, as in the present study, block or reduce the vertical transmission in HIV positive pregnant women who are coinfected with HBV. PMID:20835503

Ilboudo, Denise; Simpore, Jacques; Ouermi, Djeneba; Bisseye, Cyrille; Sagna, Tani; Odolini, Silvia; Buelli, Fabio; Pietra, Virginio; Pignatelli, Salvatore; Gnoula, Charlemagne; Nikiema, Jean-Baptiste; Musumeci, Salvatore

2010-01-01

209

The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule  

PubMed Central

Background Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age. Methods 299 healthy infants were randomised to receive either DTPw-HBV/Hib2.5 [Kft] DTPw-HBV/Hib2.5 or DTPw-HBV/Hib according to the 6-10-14 week EPI schedule. Blood samples were analysed prior to the first dose of study vaccine and one month after the third vaccine dose for the analysis of immune responses. Solicited local and general symptoms such as pain, redness and swelling at the injection site and drowsiness and fever, unsolicited symptoms (defined as any additional adverse event) and serious adverse events (SAEs) were recorded up to 20 weeks of age. Results One month after the third vaccine dose, 100% of subjects receiving DTPw-HBV/Hib2.5 [Kft] or DTPw-HBV/Hib and 98.8% of subjects receiving DTPw-HBV/Hib2.5 vaccine had seroprotective levels of anti-PRP antibodies (defined as anti-PRP antibody concentration ?0.15 ?g/ml). Seroprotective antibody concentrations were attained in over 98.9% of subjects for diphtheria, tetanus and hepatitis B. The vaccine response rate to pertussis antigen was at least 97.8% in each group. Overall, the DTPw-HBV/Hib2.5 [Kft] vaccine was well tolerated in healthy infants; no SAEs were reported in any group. Conclusions The DTPw-HBV/Hib2.5 [Kft] vaccine was immunogenic and well-tolerated when administered according to the EPI schedule to Indian infants. Trial registration http://www.clinicaltrials.gov NCT00473668

2010-01-01

210

Alkoxyalkyl Esters of 9-(S)-(3-Hydroxy-2-Phosphonomethoxypropyl) Adenine Are Potent and Selective Inhibitors of Hepatitis B Virus (HBV) Replication In Vitro and in HBV Transgenic Mice In Vivo ?  

PubMed Central

Alkoxyalkyl esters of acyclic nucleoside phosphonates have previously been shown to have increased antiviral activity when they are administered orally in animal models of viral diseases, including lethal infections with vaccinia virus, cowpox virus, ectromelia virus, murine cytomegalovirus, and adenovirus. 9-(S)-(3-Hydroxy-2-phosphonomethoxypropyl)adenine [(S)-HPMPA] was previously shown to have activity against hepatitis B virus (HBV) in vitro. To assess the effect of alkoxyalkyl esterification of (S)-HPMPA, we prepared the hexadecyloxypropyl (HDP), 15-methyl-hexadecyloxypropyl (15M-HDP), and octadecyloxyethyl (ODE) esters and compared their activities with the activity of adefovir dipivoxil in vitro and in vivo. Alkoxyalkyl esters of (S)-HPMPA were 6 to 20 times more active than unmodified (S)-HPMPA on the basis of their 50% effective concentrations in 2.2.15 cells. The increased antiviral activity appeared to be due in part to the increased uptake and conversion of HDP-(S)-HPMPA to HPMPA diphosphate observed in HepG2 cells in vitro. HDP-(S)-HPMPA retained full activity against HBV mutants resistant to lamivudine (L180M, M204V), but cross-resistance to a mutant resistant to adefovir (N236T) was detected. HDP-(S)-HPMPA is orally bioavailable and provides excellent liver exposure to the drug. Oral treatment of HBV transgenic mice with HDP-(S)-HPMPA, 15M-HDP-(S)-HPMPA, and ODE-(S)-HPMPA for 14 days reduced liver HBV DNA levels by roughly 1.5 log units, a response equivalent to that of adefovir dipivoxil.

Morrey, John D.; Korba, Brent E.; Beadle, James R.; Wyles, David L.; Hostetler, Karl Y.

2009-01-01

211

Protein ProQ influences osmotic activation of compatible solute transporter ProP in Escherichia coli K-12.  

PubMed

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

Kunte, H J; Crane, R A; Culham, D E; Richmond, D; Wood, J M

1999-03-01

212

Validation of Virus NAT for HIV, HCV, HBV and HAV Using Post-Mortal Blood Samples  

PubMed Central

Summary Objective Commercial available NAT systems are usually not validated for screening of post-mortem blood samples. NAT testing might be challenging due to inhibitory substances in the cadaveric blood sample that cause false-negative test results. Validation studies have to be performed to show the performance characteristics of the NAT assays for testing cadaveric blood. Methods A set of 32 post-mortem serum and plasma samples from cornea donors and 40 control samples from blood donors, serologically and NAT negative for all investigated parameters, were spiked with defined concentrations of WHO reference material and tested for HIV-1, HCV, HBV, and HAV by NAT using DRK Baden-Württemberg-Hesse CE PCR kits. Analytical sensitivity, analytical specificity and reproducibility/precision were validated and compared with each other in both groups of samples. Results The analytical sensitivity was 100% for control and post-mortem specimens when spiked with virus standards at concentrations of 3 × level of detection (LOD). Invalid results did not occur. The analytical specificity rate for all assays was 100%. Intra-assay variation was analyzed as a function of sample material and sampling time post mortem. Values of % coefficient of variation (%CV) were comparable for serum and plasma but slightly higher for post-mortem samples especially for those samples collected more than 24 h post mortem. Conclusion Based on the presented validation, postmortem donor samples can be tested with the automated DRK Baden-Würtemberg-Hesse NAT system.

Gubbe, Knut; Scharnagl, Yvonne; Grosch, Steffi; Tonn, Torsten; Schmidt, Michael; Hourfar, Kai M.; Karl, Andreas; Seifried, Erhard; Wilkemeyer, Ina; Kalus, Ulrich

2012-01-01

213

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

NASA Astrophysics Data System (ADS)

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.

Ding, Jie; Haberlandt, Uwe

2014-05-01

214

Anti-HBV immune responses in rhesus macaques elicited by electroporation mediated DNA vaccination.  

PubMed

Electroporation has been shown to be an effective method to improve the efficiency of gene expression and the immunogenicity of DNA vaccines. In order to optimize the procedure and test for its efficacy in more clinically relevant large animal models, we examined the detailed immune responses in rhesus macaques after vaccination intramuscularly with electroporation using the plasmid encoding for HBV preS(2)-S antigen and an adjuvant plasmid encoding for hIL-2 and hIFN-gamma. Several important factors were examined, including the dose response relationships, the effect of various prime and boost regimens, and different combinations of electro-pulse parameters. The immune responses were closely followed for more than a year. The results showed that in rhesus macaques, electroporation can significantly enhance the immunogenicity of the DNA vaccines, resulting in greatly improved antibody responses as well as peptide-stimulated IFN-gamma producing T cell responses. In addition, we also reported the different antibody response behaviors resulted from different electro-pulse parameters. The detailed data would be useful to suggest possible optimization strategies for better DNA vaccine efficacy. PMID:16253404

Zhao, Yong-Gang; Peng, Baowei; Deng, Hongwei; Chen, Guangming; Yang, Fuqiang; Shao, Ming; Lu, Huili; Li, Yufeng; Peng, Jinliang; Xu, Long; Xu, Yuhong

2006-02-13

215

A Genome-Wide Association Study on Chronic HBV Infection and Its Clinical Progression in Male Han-Taiwanese  

PubMed Central

It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P?=?4.87×10?14), rs9276370 (HLA-DQA2, P?=?1.9×10?12), rs7756516 and rs7453920 (HLA-DQB2, P?=?1.48×10?11 and P?=?6.66×10?15 respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P?=?2.58×10?10). The “T-T-G-G-T” haplotype of the five SNPs further signified their association with the disease (P?=?1.48×10?12; OR?=?1.49). The “T-T” haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P?=?0.0262). The “G-C” haplotype was associated with sustained therapeutic response (P?=?0.0132; OR?=?2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.

Chang, Su-Wei; Fann, Cathy Shen-Jang; Su, Wen-Hui; Wang, Yu Chen; Weng, Chia Chan; Yu, Chia-Jung; Hsu, Chia-Lin; Hsieh, Ai-Ru; Chien, Rong-Nan; Chu, Chia-Ming; Tai, Dar-In

2014-01-01

216

Computerized physician order entry-based system to prevent HBV reactivation in patients treated with biologic agents: The PRESCRIB project.  

PubMed

Computerized physician order entry (CPOE) applications are widely used to prevent medical errors. In our center, a CPOE system has been in use since 2009 on both the inpatient and outpatient levels. A new and simple alert was introduced in the CPOE system to notify healthcare providers of the potential risk of viral reactivation when prescribing biological therapies, thereby facilitating the request for a serological profile (hepatitis B surface antigen [HBsAg], anti-HBc, and anti-HBs) in patients who have not had these tests. Between May 2012 and May 2013, a total of 1,076 patients undergoing biological treatment were included in the implementation of the CPOE in our hospital, resulting in the identification of 4 HBsAg-positive and 69 anti-HBc-positive/HBsAg-negative patients, two of them with positive viral loads. Since the implementation of this alert system, over 90% of patients who were prescribed a biological drug (BD) have undergone serological screening to detect hepatitis B virus (HBV) infection. The use of the alert system has increased the screening rate from less than 50% to 94% for HBsAg and from less than 30% to 85% for anti-HBc in patients for whom a BD is prescribed. Six patients received prophylactic antiviral therapy. No patient had HBV reactivation. Conclusion: This study demonstrates the feasibility of implementing a CPOE system that has allowed our hospital to increase the rate of HBV screening. Its use has facilitated the identification of patients at high risk for HBV reactivation and permitted physicians to prescribe prophylactic measures according to current guidelines. (Hepatology 2014;106-113). PMID:24585503

Sampedro, Blanca; Hernández-López, Cándido; Ferrandiz, José Ramón; Illaro, Aitziber; Fábrega, Emilio; Cuadrado, Antonio; Iruzubieta, Paula; Menéndez, Susana; Cabezas, Joaquín; Crespo, Javier

2014-07-01

217

HIV, HBV, and HCV Infections Among Drug-Involved, Inner-City, Street Sex Workers in Miami, Florida  

Microsoft Academic Search

This study describes the rates of HIV, HBV, and HCV seropositivity among drug-involved, female street sex workers in low-income, inner-city sections of Miami, Florida; further, their sociodemographic characteristics, drug use, and sexual risk behaviors were assessed; and predictors of infection were reported. A sample of 586 sex workers was recruited through targeted sampling methods, interviewed, and counseled and tested for

James A. Inciardi; Hilary L. Surratt; Steven P. Kurtz

2006-01-01

218

Increased detection of HBV DNA in HBsAg-positive and HBsAg-negative South African HIV/AIDS patients enrolling for highly active antiretroviral therapy at a Tertiary Hospital.  

PubMed

This retrospective study investigated the prevalence of hepatitis B virus (HBV) in 192 stored sera from human immunodeficiency virus (HIV) positive South African patients initiating antiretroviral therapy (ART), and explored the implications of HBV-HIV co-infection on laboratory diagnosis of HBV. HBV serology (HBsAg, anti-HBs and anti-HBc) and nested HBV PCR assays targeting the HBV polymerase gene were performed, with HBV DNA positive samples being quantified with Cobas Taqman HBV test 48 assay (Roche Diagnostics). The study found that 63% (121/192) of patients had past or present HBV infection, and 40.6% (78/192) had detectable HBV DNA. Also, 22.9% (44/192) of patients were HBsAg positive and HBV DNA positive, while 23% (34/148) of HBsAG negatives had occult HBV infections. Of the 78 HBV DNA positive samples, 62.8% had viral loads ranging from 10(2) to > or =10(8) IU/ml, and 37.2% had HBV viral loads <200 IU/ml. There was a statistically significant positive association between HBsAg-positivity and high viral loads, with 27% (12/44) of HBsAg positives having HBV viral loads between 10(4) and > or =10(8) IU/ml, compared to only 5.9% (2/34) of HBsAg negatives (relative risk: 4.64; 95% confidence interval: 1.11, 19.35; chi-square P-value = 0.015). The study shows that the majority of HIV/AIDS patients initiating ART have either acute or chronic HBV infections, and further confirms that HIV remains a risk factor for occult HBV infections in South African patients as previously shown. The findings strongly support HBV screening in all HIV-positive patients initiating ART in South Africa, considering that current ART regimens include drugs with anti-HBV activity (e.g., lamivudine). PMID:19152393

Lukhwareni, Azwidowi; Burnett, Rosemary J; Selabe, S Gloria; Mzileni, M Olga; Mphahlele, M Jeffrey

2009-03-01

219

Prevalence of anti-HCV antibodies in patients with chronic liver disease and its relationship to HBV and HDV infections.  

PubMed

The prevalence of anti-HCV, anti-HDV and of HBV markers has been investigated in a series of 209 consecutive patients (age 18-74 years) with chronic liver disease. Among 155 HBsAg negative patients (53 chronic hepatitis cases and 102 cirrhosis cases), anti-HCV were found in 69% of the cases. 67% of the 155 patients also carried anti-HBc, with no difference between patients positive or negative for anti-HCV. Among the 54 HBsAg positive patients, 10 (18.5%) also had anti-HCV, 22 (40.7%) were anti-HDV positive and 12 (22.2%) had serum HBV-DNA. One patient had concomitant anti-HDV and anti-HCV and another presented anti-HCV and serum HBV-DNA. 21/54 patients had liver cirrhosis on presentation and among these 17 (81%) were anti-HCV and/or anti-HDV positive. On the whole, 123/209 patients had liver cirrhosis on presentation and in 107 of them HCV infection may have played a role. PMID:2177452

Gaeta, G B; Rapicetta, M; Sardaro, C; Spadaro, A; Chionne, F; Freni, A M; Ajello, A; Costantino, A; Giusti, G

1990-01-01

220

Drug-Resistance Associated Mutations in Polymerase (P) Gene of Hepatitis B Virus Isolated From Malaysian HBV Carriers  

PubMed Central

Background: Mutations in the polymerase (P) gene of hepatitis B virus are often associated with drug resistance. The pattern of mutations varies geographically, thus giving rise to genotypes diversity. Objectives: This study was carried out to detect mutations in P gene of hepatitis B virus isolated from Malaysian HBV carriers. Materials and Methods: A total of 58 sera samples were analyzed by PCR and sequencing, of which the P gene of isolated HBV was successfully amplified and sequenced from 40 samples. Results: Genotyping of these samples revealed that the predominant genotype was genotype C (22/40, 55.0%), followed by genotype B (17/40, 42.5%), and only 1 sample showed genotype D (2.5%). A number of significant drug resistant mutations were found in five patients including S202I, N236T, M250L, L180M/V, M204I, A181T, T184G, M250V, and V173L. Of these, L180M/V and M204I were most frequently detected (80%) and associated with lamivudine in combination with emtricitabine and telbivudine drug resistance. Association with age, sex, and clinical symptoms revealed that these patients were all male, mid to elderly age and almost all hadcirrhotic liver disease. Conclusions: Detection and surveillance of the significant sites of mutations in HBV is crucial for clinicians to decide on the choice of antiviral treatment and further management of hepatitis B carriers.

Suppiah, Jeyanthi; Mohd Zain, Rozainanee; Haji Nawi, Salbiah; Bahari, Norazlah; Saat, Zainah

2014-01-01

221

Human adipose-derived mesenchymal stem cells are resistant to HBV infection during differentiation into hepatocytes in vitro.  

PubMed

The therapeutic methods for chronic hepatitis B are limited. The shortage of organ donors and hepatitis B virus (HBV) reinfection obstruct the clinical application of orthotopic liver transplantation (OLT). In the present study, adipose-derived mesenchymal stem cells (AD-MSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) were isolated from chronic hepatitis B patients and characterized for morphology, growth potency, surface phenotype and the differentiation potential. The results showed that both MSCs had adipogenic, osteogenic and neuron differentiation potential, and nearly all MSCs expressed CD105, CD44 and CD29. Compared with AD-MSCs, BM-MSCs of chronic hepatitis B patients proliferated defectively. In addition, the ability of AD-MSCs to differentiate into hepatocyte was evaluated and the susceptibility to HBV infection were assessed. AD-MSCs could differentiate into functional hepatocyte-like cells. These cells express the hepatic-specific markers and have glycogen production and albumin secretion function. AD-MSCs and hepatic differentiation AD-MSCs were not susceptible to infection by HBV in vitro. Compared with BM-MSCs, AD-MSCs may be alternative stem cells for chronic hepatitis B patients. PMID:24727377

Wang, Ying; Wang, Feng; Zhao, Hongchang; Zhang, Xiaohe; Chen, Haiying; Zhang, Kaiyu

2014-01-01

222

Genetic Editing of HBV DNA by Monodomain Human APOBEC3 Cytidine Deaminases and the Recombinant Nature of APOBEC3G  

PubMed Central

Hepatitis B virus (HBV) DNA is vulnerable to editing by human cytidine deaminases of the APOBEC3 (A3A-H) family albeit to much lower levels than HIV cDNA. We have analyzed and compared HBV editing by all seven enzymes in a quail cell line that does not produce any endogenous DNA cytidine deaminase activity. Using 3DPCR it was possible to show that all but A3DE were able to deaminate HBV DNA at levels from 10?2 to 10?5 in vitro, with A3A proving to be the most efficient editor. The amino terminal domain of A3G alone was completely devoid of deaminase activity to within the sensitivity of 3DPCR (?10?4 to 10?5). Detailed analysis of the dinucleotide editing context showed that only A3G and A3H have strong preferences, notably CpC and TpC. A phylogenic analysis of A3 exons revealed that A3G is in fact a chimera with the first two exons being derived from the A3F gene. This might allow co-expression of the two genes that are able to restrict HIV-1?vif efficiently.

Henry, Michel; Guetard, Denise; Suspene, Rodolphe; Rusniok, Christophe; Wain-Hobson, Simon; Vartanian, Jean-Pierre

2009-01-01

223

A Study on the HBV and the HCV Infections in Female Sex Workers and their Co-Infection with HIV  

PubMed Central

Background: Sexually Transmitted Infections (STIs) have been shown to enhance the transmission of the Human Immunodeficiency Virus (HIV). The Hepatitis B and the Hepatitis C viral infections are highly prevalent among the HIV-infected persons as a result of shared transmission routes. Aim: To determine the seroprevalence of the HIV, Syphilis, HBV and HCV infections and their co-infection rates among Female Sex Workers (FSWs). Settings and Design: 250 blood samples were collected from FSWs from a red light area of Mumbai by using an outreach strategy. Materials and Methods: Their sera were tested for the HIV antibodies as per the strategy II of the NACO guidelines, for syphilis by RPR, for the HCV antibodies and for HBsAg by ELISA. Results: The study group showed (105/250) 42% HIV reactivity, (15/250) 6% RPR reactivity, (20/250) 8% HBsAg positivity, (7/250) 2.8% HCV reactivity, (11/250) 4.4% HIV-RPR reactivity, (7/250) 2.8% HIV-HBV co-infection and (3/250)1.2% HIV-HCV co-infection. Statistical test which was used: The Chi square test. Conclusion: A high HIV sero-prevalence was found among the FSWs. A high HIV prevalence was found among the RPR reactive FSWs. The relationship between the HIV reactivity and the RPR reactivity was statistically significant. Co-infections with HBV and HCV were detected among the HIV reactive FSWs, but they were not statistically significant.

Praseeda S., Desai; Anuradha, Dutta; Jayanthi S., Shastri

2013-01-01

224

Human Adipose-Derived Mesenchymal Stem Cells Are Resistant to HBV Infection during Differentiation into Hepatocytes in Vitro  

PubMed Central

The therapeutic methods for chronic hepatitis B are limited. The shortage of organ donors and hepatitis B virus (HBV) reinfection obstruct the clinical application of orthotopic liver transplantation (OLT). In the present study, adipose-derived mesenchymal stem cells (AD-MSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) were isolated from chronic hepatitis B patients and characterized for morphology, growth potency, surface phenotype and the differentiation potential. The results showed that both MSCs had adipogenic, osteogenic and neuron differentiation potential, and nearly all MSCs expressed CD105, CD44 and CD29. Compared with AD-MSCs, BM-MSCs of chronic hepatitis B patients proliferated defectively. In addition, the ability of AD-MSCs to differentiate into hepatocyte was evaluated and the susceptibility to HBV infection were assessed. AD-MSCs could differentiate into functional hepatocyte-like cells. These cells express the hepatic-specific markers and have glycogen production and albumin secretion function. AD-MSCs and hepatic differentiation AD-MSCs were not susceptible to infection by HBV in vitro. Compared with BM-MSCs, AD-MSCs may be alternative stem cells for chronic hepatitis B patients.

Wang, Ying; Wang, Feng; Zhao, Hongchang; Zhang, Xiaohe; Chen, Haiying; Zhang, Kaiyu

2014-01-01

225

Several concerns about the primer design in the universal molecular beacon real-time PCR assay and its application in HBV DNA detection  

Microsoft Academic Search

A universal hepatitis B virus (HBV) DNA detection kit is appealing for the worldwide diagnosis and monitoring of the treatment\\u000a of different mutant types of hepatitis B virus. A sensitive and reproducible real-time PCR assay based on the universal molecular\\u000a beacon (U-MB) technique was developed for the detection of HBV DNA in serum. The U-MB probe used in the assay

Xiaomin Li; Yong Huang; Chen Song; Meiping Zhao; Yuanzong Li

2007-01-01

226

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

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

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

227

HBV, HCV, and TTV detection by in situ polymerase chain reaction could reveal occult infection in hepatocellular carcinoma: comparison with blood markers  

PubMed Central

Objective To report a retrospective analysis on the presence of hepatitis B virus (HBV), hepatitis C virus (HCV), and transfusion transmitted virus (TTV) sequences in formalin fixed, paraffin embedded liver biopsies from eight patients with hepatocellular carcinoma, in comparison with blood markers. Methods A direct in situ polymerase chain reaction (PCR) technique was developed for the detection and localisation of genomic signals in the liver tissue. Conventional serological and molecular methods were used for blood evaluation. Results In situ PCR showed the presence of one of the three viruses (four HCV, two HBV, and one TTV) in seven of the eight patients. In addition, a co?infection with HBV and HCV was detected in one patient. HCV and HBV sequences were located in the cytoplasm and the nucleus, respectively. When compared with blood markers, these findings were compatible with one occult HBV and two occult HCV infections. Conclusions These findings provide further evidence for occult HBV and HCV infections in cancerous tissues from patients with hepatocellular carcinomas. In situ PCR could be an additional tool for evaluating the viral aetiology of hepatocellular carcinoma alongside conventional diagnostic procedures.

Comar, M; Molin, G Dal; D'Agaro, P; Croce, S L; Tiribelli, C; Campello, C

2006-01-01

228

Mutations in pre-core and basal-core promoter regions of hepatitis B virus in chronic HBV patients from Golestan, Iran  

PubMed Central

Objective(s): It has been reported that the mutation of the pre-core (PC) and basal-core promoter (BCP) may play an important role in the development of HBV-related hepatocellular carcinoma (HCC). In this study the PC and BCP mutations were investigated in chronic HBV patients. Materials and Methods: In this study, 120 chronic HBV patients from Golestan, Northeast of Iran who were not vaccinated against HBV, were recruited from the year 2008 to 2012. HBV-DNA extraction from plasma and PCR were performed and positive PCR products were subjected to automated sequencing. Results: One hundred out of 120 (83.3%) patients were HBeAg negative. Comparison of our nucleotide sequences with reference sequence showed high rate mutation in BCP and PC region (96.66%). Frame shift mutation was found in 78 (65%) of patients in BCP region, among them 8 (6.6%) patients showed mutation in PC region. Conclusion: Our results demonstrated high rate of mutations in BCP and PC regions among HBV chronic patients in Northeast of Iran.

Moradi, Abdolvahab; Zhand, Sareh; Ghaemi, Amir; Javid, Naeme; Bazouri, Masoud; Tabarraei, Alijan

2014-01-01

229

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

PubMed Central

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 were age between 25–46, fale gender, being unmarried, being employed in prison service for longer than median duration of employment of 10 years, and history of sexually transmitted diseases. Conclusion The comparably higher prevalence of HIV, HBV, HCV and syphilis in prison inmates and officers in Ghana suggests probable occupational related transmission. The implementation of infection control practices and risk reduction programs targeted at prison inmates and officers in Ghana is urgently required to address this substantial exposure risk.

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

230

Expansion of circulating TFH cells and their associated molecules: involvement in the immune landscape in patients with chronic HBV infection  

PubMed Central

Background Blood CXCR5+CD4+ T cells are defined as circulating T follicular helper (TFH) cells, which is required for effective humoral immunity. This study aimed to investigate the role of circulating TFH cells in patients with chronic hepatitis B virus (CHB) infection. Methods The frequency and phenotype of circulating TFH cells were monitored by flow cytometry in CHB patients and in healthy controls (HC). The expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA was analyzed using real-time PCR. Serum HBsAg, HBeAg, HBeAb, HBV DNA loads, ALT and AST were determined. The potential association of the frequency of TFH cells and their surface markers with clinical parameters was assessed. Results The frequency of CXCR5+CD4+ T cells was increased in CHB patients and positively correlated with ALT and AST but not with HBV DNA loads. Moreover, an expansion of ICOS-, PD-1-, CD40L-, and IL-21R-expressing TFH cells occurred in CHB patients, but failed to correlate with ALT, AST and HBV DNA loads. Interestingly, the frequency of CXCR5+CD4+ T cells and ICOS+CXCR5+CD4+ T cells was significantly higher in HBeAg positive CHB patients than in HC. Additionally, the percentages of CXCR5+CD4+ T cells were positively correlated with AST, and ICOS-expressing CXCR5+CD4+ T cells were negatively correlated with HBV DNA loads. No significant differences in the frequency of CXCR5+CD4+ T cells were observed between inactive carrier (IC) patients and healthy controls. However, ICOS-, PD-1-, CD40L-expressing TFH cells were increased in IC patients and positively correlated with AST. Furthermore, the expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA in TFH cells was higher in CHB patients than in HC. Conclusions These data demonstrate that circulating TFH cells may participate in HBV-related immune responses. In addition to the frequency of TFH cells, the phenotype of these cells plays an important role in CHB patients.

2014-01-01

231

Assimilating H-SAF and MODIS Snow Cover Data into the Conceptual Models HBV and SRM  

NASA Astrophysics Data System (ADS)

Conceptual hydrological models are widely used for operational and scientific water resources management applications in mountain catchments. However, current model-based forecasting approaches are jeopardized by input data and model uncertainties. Data assimilation provides a suitable tool to merge information from remotely sensed observations and hydrological model predictions for improving the lead time performance of streamflow forecasts in the context of operational hydrological forecasting systems. In this study, we present a novel variational approach based on Moving Horizon Estimation (MHE). It includes a highly flexible formulation of distance metrics for penalizing the introduction of noise into the model and enforcing the agreement between simulated and observed variables. Furthermore, the MHE setup shows a high robustness regarding non-equidistant, noisy and sometimes missing data and enables the modification of model input as well as state variables. In situ snowpack measurements are sparsely distributed in mountainous regions. Therefore the data limitations in combination with snowpack heterogeneity prevent a detailed understanding of the variability of snow cover and melt. Remotely sensed images offer an opportunity to supplement ground measurements for performing runoff predictions during the snowmelt season. In this context, EUMETSAT initiated the H-SAF (Satellite Application Facility on Support to Operational Hydrology and Water Management) project for deriving novel products from satellite data and applying it to operational hydrology. This research contributes to the H-SAF product validation by applying a generic data assimilation test bed for H-SAF snow products in comparison to snow cover data of MODIS. A preliminary performance assessment of the data assimilation framework using the conceptual models HBV and SRM with satellite derived snow data is evaluated for a snow dominated test site of 10250 km2 at the headwaters of Euphrates River in Turkey.

Sensoy, Aynur; Schwanenberg, Dirk; Sorman, Arda; Akkol, Bulut; Alvarado Montero, Rodolfo; Uysal, Gokcen

2014-05-01

232

Human Tryptase Cleaves Pro-Nerve Growth Factor (Pro-NGF)  

PubMed Central

Several factors regulate nerve growth factor (NGF), which is formed from pro-NGF by intracellular and extracellular enzymatic cleavage. The close proximity between mast cells expressing the protease tryptase and NGF-producing smooth muscle-like peritubular cells in the testes of infertile patients led us to examine whether tryptase is among those factors. Human peritubular cells express functional tryptase receptors (PAR-2). Recombinant enzymatically active ?-tryptase increased NGF levels in the culture medium of primary human peritubular cells, but the peptide agonist for PAR-2 (SLIGKV) did not. Neither tryptase nor the peptide increased NGF mRNA levels. To test whether the increase in NGF is due to enzymatic activity of tryptase acting on pro-NGF, supernatants of peritubular cells and synthetic pro-NGF were treated with tryptase. Results of Western blot studies indicate enzymatic cleavage of pro-NGF by active tryptase. Heat-inactivated tryptase or SLIGKV was not effective. Mass spectrometry analysis of in vitro cleavage products from recombinant tryptase and synthetic pro-NGF revealed multiple cleavage sites within the pro-NGF sequence. The results also indicate the generation of mature NGF and smaller NGF fragments as a result of tryptase action. Thus, tryptase-secreting mast cells in the vicinity of pro-NGF/NGF-secreting cells in any human tissue are likely able to alter the ratios of pro-NGF/NGF. As NGF and pro-NGF have different affinities for their receptors, this indicates a novel way by which mast cells, via tryptase, can modify the microenvironment in human tissues with regard to neurotrophin actions.

Spinnler, Katrin; Frohlich, Thomas; Arnold, Georg J.; Kunz, Lars; Mayerhofer, Artur

2011-01-01

233

Network of hydrogen bonds in Pro-Ala-Pro and Pro-Phe-Pro diamides: A first principles study of Ala-->Phe point mutation in proline environment  

NASA Astrophysics Data System (ADS)

Intramolecular hydrogen bonding in the Pro-Ala-Pro and Pro-Phe-Pro tripeptides has been characterized using Bader's atoms in molecule (AIM) analyses of relevant electron density topologies. The properties of hydrogen bonds with corresponding ring strains were investigated. Good correlations along the decrease in electron densities at ring critical points were examined from five- to ten-membered hydrogen-bound ring sizes; seven-membered rings being the most energetically favored. AIM analysis confirms the logical conclusion that the molecule has to become very compact to form as many hydrogen bonds as possible. The relatively large hydrogen bond stabilization attributed to the pronounced network of interactions comes at the ``energetic expense'' of a relatively large internal repulsion due to the compactness of the structures. The net balanced result was a very modest increase in the zero point corrected conformation energy (?EZPEC). These findings aid in establishing hydrogen bonding rules in reductionist ``bottoms-up'' approaches to peptide and protein folding.

Wang, Hui; Csizmadia, Imre G.; Marsi, Istvan; Chasse, Gregory A.; Fang, Decai; Viskolcz, Bela

2009-07-01

234

Pro and prebiotics - the tasty guardian angels?  

Microsoft Academic Search

It is generally accepted that the bacterial community resident in the human intestinal tract has a major impact on gastrointestinal function and thereby on human health and well-being. Considerable efforts have been made to influence the intestinal microbiota by dietary means in such a way that the health of the host is beneficially affected. Pro- and prebiotics are food products

Rainer Simmering; Michael Blaut

2001-01-01

235

A Pro-Family Income Tax.  

ERIC Educational Resources Information Center

Discusses the Tax Reform Act of 1986, which doubled the personal exemption, increased the eligibility ceiling for the Earned Income Tax Credit, and reduced marginal income-tax rates. Compares the Act with the Acts of 1948 and 1969. Outlines criteria for a pro-family income tax policy. (BJV)

Carlson, Allan

1989-01-01

236

Neutrophil Gelatinase-Associated Lipocalin (NGAL), Pro-Matrix Metalloproteinase-9 (pro-MMP-9) and Their Complex Pro-MMP-9/NGAL in Leukaemias  

PubMed Central

Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro)-MMP-9 (active and latent forms) and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro)-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro)-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

Bouchet, Sandrine; Bauvois, Brigitte

2014-01-01

237

Comparison of the cytotoxic, pro-oxidant and pro-inflammatory characteristics of different oxysterols  

Microsoft Academic Search

Oxidized low-density lipoproteins play important roles in the development of atherosclerosis and contain several lipid-derived, bioactive molecules which are believed to contribute to atherogenesis. Of these, some cholesterol oxidation products, refered to as oxysterols, are suspected to favor the formation of atherosclerotic plaques involving cytotoxic, pro-oxidant and pro-inflammatory processes. Ten commonly occurring oxysterols (7?-, 7?-hydroxycholesterol, 7-ketocholesterol, 19-hydroxycholesterol, cholesterol-5?,6?-epoxide, cholesterol-5?,6?-epoxide, 22R-,

S. Lemaire-Ewing; C. Prunet; T. Montange; A. Vejux; A. Berthier; G. Bessède; L. Corcos; P. Gambert; D. Néel; G. Lizard

2005-01-01

238

Seroprevalence of HIV, HBV, HCV and syphilis infections among blood donors at Gondar University Teaching Hospital, Northwest Ethiopia: declining trends over a period of five years  

PubMed Central

Background Transfusion-transmissible infectious agents such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis are among the greatest threats to blood safety for the recipient. This study aimed to determine the seroprevalence, risk factors and trends of HIV, HBV, HCV and syphilis infections among blood donors over a period of five years at Gondar University Teaching Hospital, Northwest Ethiopia. Methods A retrospective analysis of consecutive blood donors' records covering the period between January 2003 and December 2007 was conducted. Logistic regression analysis was used to determine risk factors associated with HIV, HBV, HCV and syphilis infections. Results From the total of 6361 consecutive blood donors, 607 (9.5%) had serological evidence of infection with at least one pathogen and 50 (0.8%) had multiple infections. The overall seroprevalence of HIV, HBV, HCV and syphilis was 3.8%, 4.7%, 0.7%, and 1.3% respectively. Among those with multiple infections, the most common combinations were HIV - syphilis 19 (38%) and HIV - HBV 17 (34%). The seropositivity of HIV was significantly increased among female blood donors, first time donors, housewives, merchants, soldiers, drivers and construction workers. Significantly increased HBV seropositivity was observed among farmers, first time donors and age groups of 26 - 35 and 36 - 45 years. Similarly, the seroprevalence of syphilis was significantly increased among daily labourers and construction workers. Statistically significant association was observed between syphilis and HIV infections, and HCV and HIV infections. Moreover, significantly declining trends of HIV, HCV and syphilis seropositivity were observed over the study period. Conclusions A substantial percentage of the blood donors harbour HIV, HBV, HCV and syphilis infections. Strict selection of blood donors and comprehensive screening of donors' blood using standard methods are highly recommended to ensure the safety of blood for recipient.

2010-01-01

239

Plant expression, lyophilisation and storage of HBV medium and large surface antigens for a prototype oral vaccine formulation.  

PubMed

Current immunisation programmes against hepatitis B virus (HBV) increasingly often involve novel tri-component vaccines containing-together with the small (S-HBsAg)-also medium and large surface antigens of HBV (M- and L-HBsAg). Plants producing all HBsAg proteins can be a source of components for a potential oral 'triple' anti-HBV vaccine. The objective of the presented research was to study the potential of M/L-HBsAg expression in leaf tissue and conditions of its processing for a prototype oral vaccine. Tobacco and lettuce carrying M- or L-HBsAg genes and resistant to the herbicide glufosinate were engineered and integration of the transgenes was verified by PCR and Southern hybridizations. M- and L-HBsAg expression was confirmed by Western blot and assayed by ELISA at the level of micrograms per g of fresh weight. The antigens displayed a common S domain and characteristic domains preS2 and preS1 and were assembled into virus-like particles (VLPs). Leaf tissues containing M- and L-HBsAg were lyophilised to produce a starting material of an orally administered vaccine formula. The antigens were distinctly sensitive to freeze-drying conditions and storage temperature, in the aspect of stability of S and preS domains and formation of multimeric particles. Efficiency of lyophilisation and storage depended also on the initial antigen content in plant tissue, yet M-HBsAg appeared to be approximately 1.5-2 times more stable than L-HBsAg. The results of the study provide indications concerning the preparation of two other constituents, next to S-HBsAg, for a plant-derived prototype oral tri-component vaccine against hepatitis B. PMID:22246107

Pniewski, Tomasz; Kapusta, Józef; Boci?g, Piotr; Kostrzak, Anna; Fedorowicz-Stro?ska, Olga; Czy?, Marcin; Gdula, Micha?; Krajewski, Pawe?; Wolko, Bogdan; P?ucienniczak, Andrzej

2012-03-01

240

Tenofovir (TDF) has stronger antiviral effect than adefovir (ADV) against lamivudine (LAM) - resistant hepatitis B virus (HBV)  

Microsoft Academic Search

Objectives  We retrospectively compared the antiviral effect of tenofovir disoproxil fumarate (TDF) with that of adefovir dipivoxil (ADV)\\u000a for patients with chronic hepatitis B (CHB) who developed resistance to lamivudine (LAM).\\u000a \\u000a \\u000a \\u000a Materials and methods  One hundred nine patients (86 males), all Asian-American except 1 Caucasian male, with LAM resistance received TDF or ADV.\\u000a HBV DNA levels were measured every 3 months. The HBeAg

Hie-Won Hann; Hee Bok Chae; Stephen R. Dunn

2008-01-01

241

Abbott RealTime HBV Assay Is More Sensitive in Detection of Low Viral Load and Little Impacted by Drug Resistant Mutation in Chronic Hepatitis B Patients under Nucleot(s)ide Analogues Therapy  

PubMed Central

Background Selection of drug-resistant strains may lead to failure of HBV antiviral therapy. There is little information whether there is detection difference in drug resistant mutations between different viral load assays of HBV. Objectives This study is aimed to investigate whether there is drug-resistant strains related detection difference between Abbott RealTime HBV (RealTime) and CobasAmpliPrep/CobasTaqMan HBV assays 2.0 (TaqMan). Study Design One hundred and thirty-four CHB patients who received HBV anti-viral therapy were enrolled. HBV virological markers were tested 3 months apart regularly. Serum HBV DNA levels were determined using the TaqMan and RealTime. YMDD (rt180M and rt204V) mutation was checked in patients who experienced virologic breakthrough (VBT). Results The correlation of HBV DNA observed between the RealTime and TaqMan was good for all 571 samples (R2?=?0.797; P<0.001). However, the correlation in the 434 samples with HBV DNA level <3 log10 IU/ml was not as good as in all samples (R2?=?0.457). Overall, 21.5% of samples had a detection difference of ?1 log10 IU/ml with 91.9% of these having HBV DNA level <3 log10 IU/ml. Twenty-four patients experiencedVBT. Three of these patients had acquired the YMDD mutation and exhibited discordant viral load results between the two methods tested. In each case, persistent HBV DNA was detected by RealTime and undetectable with TaqMan. Of the patients who experienced a VBT and had acquired YMDD mutation, 4.7% had undetectable HBV DNA by TaqMan while all were detectable with RealTime. Conclusions RealTime assay is more sensitive and is little impacted by the development of drug resistant mutation.

Yeh, Ming-Lun; Huang, Chung-Feng; Huang, Ching-I; Liu, Shu-Fen; Yang, Hua-Ling; Hsieh, Ming-Yen; Huang, Jee-Fu; Dai, Chia-Yen; Chuang, Wan-Long; Yu, Ming-Lung

2014-01-01

242

[Radiation Anticarcinogenesis by Thiazolidine Pro-drug  

NASA Technical Reports Server (NTRS)

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.

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

1999-01-01

243

Hepatitis B virus: molecular genotypes and HBeAg serological status among HBV-infected patients in the southeast of Brazil  

PubMed Central

Background Knowledge of HBV genotype is very important for clinical treatment. Studies have suggested possible pathogenic and therapeutic differences among HBV genotypes. The aim of this study was to determine HBV subtypes and genotypes in HBV-infected patients in our region (southeast Brazil) and to correlate results with clinical and histopathological data. Methods One hundred and thirty-nine HBsAg-positive patients were included in the study. All patients were anti-HCV and anti-HIV negative (64% male; mean age 42 ± 14.5 years; range 7-80 years; 84% Caucasian) and were followed up at the University Hospital. A method for genotyping and subtyping HBV by partial HBsAg gene sequencing with primers common to all known genotypes was used. The viral load was measured by Amplicor Monitor assay (Roche). Results HBV genotype A was the most prevalent (55%), while genotypes C, D and F were found in 3%, 38% and 4% of HBV-infected patients, respectively. Among the patients infected by genotype A, 18.3% (14/76) were African descendents and, among the patients infected by genotype D, 11.3% (6/53) were also African descendents. In the four patients infected with genotype C, 2 were Asian descendents and 2 were Caucasians. All (7) genotype F infected patients were Caucasians. Seventy percent of our HBsAg-positive patients were HBeAg negative (62% genotypes A; 26.2% D; 7.1% C and 4.7%F). The viral load of HBV-DNA was about 5 times higher in HBeAg-positive than in HBeAg-negative patients. About 40% of these patients had alanine aminotransferase of up to 1.5 times the normal level. The mean stage of fibrosis in genotype A patients (2.8) was significantly higher than the mean stage of fibrosis in genotype D patients (2.0) (P = 0.0179). Conclusion The genotypes encountered in our HBV-infected patients were apparently a consequence of the types of immigration that occurred in our region, where European and African descendents predominate. The HBeAg-negative status predominated, possibly due to the length of time of infection. The viral load in HBeAg-positive patients was higher than in HBeAg-negative individuals. The fibrosis grade in genotype A-infected patients was more advanced than genotype D-infected patients.

2009-01-01

244

Progesterone withdrawal I: pro-convulsant effects  

Microsoft Academic Search

Pro-convulsant withdrawal properties have been reported for a variety of GABA-modulatory drugs, such as the benzodiazepines (BDZs, [S.E. File, The history of BDZ dependence: a review of animal studies, Neurosci. Biobehav. Rev. 14 (1990) 135–146; P.R. Finley, P.E. Nolan, Precipitation of BDZ withdrawal following sudden discontinuation of midazolam, DICP 23 (1989) 151–152]), barbiturates and ethanol [N. Kokka, D.E. Sapp, U.

Maria H. Moran; Sheryl S. Smith

1998-01-01

245

Pro-Life nurses uniting for service.  

PubMed

The Missouri Pro-Life Nurses claim that nurses have lost the ethical basis of their profession. Nurses need to reexamine their attitudes at a time when 1 in 5 physician-members of the American Society of Internal Medicine admits to deliberately helping a patient end his or her life, and when many physicians and nurses favor euthanasia and abortion. Former Georgia nurse Joseph Dewey Akin was sentenced in October 1992 to life imprisonment for injecting Robert Price, a quadriplegic, with a lethal dose of lidocaine. Hospice nurse Darlene Leon of California is on trial for injecting 17 of her patients with lethal doses of morphine. A nurse from Georgia was indicted on one count of aggravated assault for attempting to kill her 87-year-old patient with an injection of potassium. Georgia nurse Jenny Serbes was charged with murder in the death of her husband with a lethal injection of insulin. The fierce argument about abortion and euthanasia now raging in America is this century's civil war. 20 years ago, in an effort to combat this tide, the National Association of Pro-Life Nurses (NAPN) was started, and its 1000 members want to demonstrate positive concern for all human life. NAPN attempts to educate nurses and the health care community on the legal and medical aspects of the ethical issues facing the profession. In October 1993 the first meeting of Illinois Pro-Life Nurses was held in suburban Chicago. The nurse-patient relationship can be viewed as a contract. Implicit in this relationship is the understanding that the nurse will do no harm. If the relationship is broken, the foundation on which nursing and medicine rest is shaken. Pro-life nursing organizations are trying to steer the nursing profession back on the right course. PMID:8006780

Sutherland, K

1994-01-01

246

31 CFR 50.93 - Application of pro rata share.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Application of pro rata share. 50.93 Section 50.93 ...Liability § 50.93 Application of pro rata share. An insurer shall apply the PRLP to determine the pro rata share of each insured loss...

2010-07-01

247

Two States of the Triple Helix in the Thermal Transition of the Collagen Model Peptide (Pro-Pro-Gly)10  

Microsoft Academic Search

The collagen model peptide (Pro-Pro-Gly)10 is known to fold into a triple helix in solution. So far, the triple helix has been considered to exist as a single state. However, our previous study of (Pro-Pro-Gly)10 in solution has indicated the presence of two different states of the triple helix, a lower (HL) and a higher temperature state (HH). In the

Tsutomu Kai; Susumu Uchiyama; Yoshinori Nishi; Yuji Kobayashi; Tetsuo Tomiyama

2004-01-01

248

T cell subsets in patients with acute and chronic HBV infection, primary biliary cirrhosis and alcohol induced liver disease.  

PubMed

The proportions of inducer and cytotoxic/suppressor T cells and their concentration in peripheral blood have been determined in patients with acute and chronic type B hepatitis, hepatitis B virus (HBV) carriers with normal hepatic histology, patients with alcohol-induced liver disease (ALD), primary biliary cirrhosis (PBC) and chronic extrahepatic cholestasis. During acute type B hepatitis the inducer/suppressor ratio was decreased due to an increase in suppressor cell concentrations. When this ratio returned to normal the HBs antigen was cleared and HBs antibody was detectable. Similar abnormalities were found in patients with HBs + ve chronic hepatitis. In HBs antigen-positive patients with normal histology, normal T cell subsets were found. In some patients with primary biliary cirrhosis the ratio of inducer to suppressor cells was low due to a reduction in the concentration of inducer cells and in others high due to a reduction in suppressor cells. Administration of cyclosporin A to the latter group produced an increase in the concentration of suppressor cells and there was an improvement in liver biochemistry. In alcohol-induced hepatitis and cirrhosis the ratio of inducer/suppressor cells was normal. Whether these imbalances of the regulatory cells of the immune system in patients with chronic HBV-induced hepatitis and PBC are of primary or secondary importance is uncertain. The relationship of the depressed ratio to persistence of the hepatitis B virus is worthy of further study. PMID:6457007

Thomas, H C

1981-01-01

249

A non-radioactive diagnostic test for the detection of HBV DNA sequences in serum at the single molecule level.  

PubMed

A non-radioactive diagnostic test, using an acetylaminofluorene-labelled DNA probe, was developed to detect HBV DNA sequences in serum. In vitro enzymatic amplification was employed to increase the amount of HBV DNA sequences, and an amplification rate up to 1.5 x 10(7) was observed. When a dot-blot was performed after amplification with the Klenow fragment for 32 cycles, the detection limit was 3-30 particles. Sera from 20 blood donors and 10 HBs-Ag carriers were screened simultaneously, with the non-radioactive test performed after 28 amplification cycles, and with the classical radioactive test without amplification. An acceptable correlation was obtained between these two techniques. In Southern blot analysis of samples amplified with the thermoresistant DNA polymerase (Taq polymerase) for 40 cycles, a single DNA molecule was detected. Thermal treatment at 115 degrees C efficiently disrupted purified viral particles and allowed the detection of a single viral particle. Applied to crude serum, a kinetic study showed that this treatment was optimal after an incubation time of up to 10 min. Under these conditions, the detection limit was approximately 2 x 10(5) viral particles, after 40 amplification cycles performed with the Taq polymerase. PMID:2733699

Larzul, D; Chevrier, D; Guesdon, J L

1989-03-01

250

The silence of MUC2 mRNA induced by promoter hypermethylation associated with HBV in Hepatocellular Carcinoma  

PubMed Central

Background To evaluate the promoter methylation status of MUC2 gene and mRNA expression in patients with hepatocellular carcinoma. Methods We analyzed MUC2 methylation by MSP, and MUC2 mRNA by real-time PCR in 74 HCC. Results MUC2 mRNA were lower in HCC tissues (Mean -?Ct?=??4.70) than that in Non-HCC tissues (Mean -?Ct?=??2.98). Expression of MUC2 was elevated in only 23 (31.08%) of the 74 HCC patients. MUC2 promoter was hypermethylated in 62.2% (46/74) of HCCs, and in only 18.9% (14/74) of non-tumor samples. MUC2 mRNA were lower in HCC patients with hypermethylation (Mean -??Ct?=??2.25) than those with demethylation (Mean -??Ct?=??0.22), and there is a decreased tendency for MUC2 mRNA in HCC patients with promoter hypermethylation (p?=?0.011). There was a significantly correlation found between MUC2 mRNA and HBV and AFP in HCC. The loss of MUC2 mRNA and hypermethylation could be poor prognostic factors. After treated by 5-Aza-CdR and TSA, we found that MUC2 mRNA induced significantly in 7721, Huh7 and HepG2 cells. Conclusion The results suggested that MUC2 mRNA silenced by promoter hypermethylation is associated with high levels HBV in HCC.

2013-01-01

251

A low proportion of HBeAg among HBsAg-positive pregnant women with known HIV status could suggest low perinatal transmission of HBV in Cameroon  

PubMed Central

Background Transmission of hepatitis B virus (HBV) from HBV-positive mothers to their infants is common and usually occurs when the mother is hepatitis B e antigen (HBeAg) positive and/or has a high HBV DNA load. In this study, we determined the prevalence of hepatitis B surface antigen (HBsAg) and HBeAg among pregnant women with known HIV status. Findings A total of 650 pregnant women with a mean age of 26.2 years including 301 HIV-positives and 349 HIV-negatives were screened for HBsAg (Monolisa AgHBs Plus Biorad, France). Among the HBsAg-positives, HBeAg and anti-HBe were tested (Monolisa Ag HBe Plus Biorad, France). Overall, 51 (7.85%) were positive for HBsAg. The prevalence of HBsAg was not statistically different between HIV-positive and HIV-negative pregnant women [28/301 (9.3%) vs 23/349 (6.59%); p = 0.2]. None of the 45 HBsAg-positive samples was reactive for HBeAg. Conclusions Our study indicates a high prevalence of HBsAg with very low proportion of HBeAg in Cameroonian pregnant women. Since perinatal transmission of HBV is mostly effective when the mother is also HBeAg-positive, our data could suggest that perinatal transmissions play a minor role in HBV prevalence in Cameroon. In line with previous African studies, these findings further suggests that horizontal transmission could be the most common mechanism of HBV infections in Cameroon.

2012-01-01

252

Evaluation of HBV DNA decay kinetics in patients containing both rtM204V/I mutant and wild-type HBV subpopulations during tenofovir DF (TDF) monotherapy or combination therapy with emtricitabine (FTC)/TDF.  

PubMed

Tenofovir disoproxil fumarate (TDF) is recommended as treatment for chronic hepatitis B patients harboring lamivudine-associated resistance mutations (LAM-R, rtM204V/I?±?rtL180M). This study evaluated the clinical response of rtM204V and rtM204I subpopulations to TDF by comparing their early viral load decay kinetics to wild-type (WT) subpopulations in chronic hepatitis B patients harboring rtM204V/I prior to initiating TDF or emtricitabine (FTC)/TDF therapy. Allele-specific PCR assays capable of detecting rtM204V or rtM204I subpopulations as low as 0.5% were developed and used to assess patient samples from a Phase 3b study evaluating TDF and FTC/TDF treatment in LAM-R patients. Baseline samples (n?=?280) were quantified for rtM204V/I subpopulations and rtM204V or rtM204I subpopulations were detected in 269/273 (98.5%) baseline samples with a range of 0.7% to >95%. On-treatment analyses were conducted for seventeen patients (TDF, n?=?8; FTC/TDF, n?=?9) that harbored baseline WT and either rtM204V or rtM204I (no rtM204V/I mixtures) and HBV DNA ?1,000?copies/ml at/after week 4. The median change in HBV DNA through week 12 for WT and rtM204V/I subpopulations was similar, -2.64 and -3.30?log10 ?copies/ml, respectively, with no significant difference between TDF and FTC/TDF treatment. In conclusion, rtM204V/I subpopulations demonstrate similar early HBV DNA decline kinetics to WT subpopulations during treatment with either TDF or FTC/TDF. These results demonstrate that TDF is similarly active against both WT and rtM204V/I subpopulations in vivo. J. Med. Virol. 86:1473-1481, 2014. © 2014 Wiley Periodicals, Inc. PMID:24861361

Liu, Yang; Fung, Scott; Gane, Edward J; Dinh, Phillip; Flaherty, John F; Svarovskaia, Evguenia S; Miller, Michael D; Kitrinos, Kathryn M

2014-09-01

253

Educational Opportunities in Pro-Am Collaboration  

NASA Astrophysics Data System (ADS)

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.

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

2006-08-01

254

[Pro and contra discussion about medical education].  

PubMed

Since the end of the last century, medical education is being renewed in many countries. There is a tendency toward integration of clinical and preclinical knowledge, presentation of basic science topics as themes of organ systems in conjunction with clinical cases, emphasis on professional attitude, context-related and small-scale learning and the own responsibility of the student. As a contribution to the discussion, the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine) and the Tijdschrift voor Medisch Onderwijs (Dutch Journal of Medical Education) have decided to publish articles in a pro and contra format. PMID:16538847

Borleffs, J C C

2006-02-25

255

A comparison of SRM and HBV models for real time runoff forecasting in the Upper Euphrates Basin, Turkey  

NASA Astrophysics Data System (ADS)

Predicting snowmelt runoff in the mountainous eastern part of Turkey at a daily time step is important in water resource management as it constitutes nearly 2/3 in volume of the total yearly runoff during spring and early summer months. Keeping track of snow dynamics as well as forecasting the amount and timing of snowmelt runoff in the headwaters of the trans-boundary Euphrates River, where large dams are located, is a crucial and challenging task concerning the practical importance and great demand for real time forecasting of melt water. In mountainous regions, data limitations prevent detailed understanding of the variability of snow cover and melt. In situ snowpack measurements are sparsely distributed relative to snowpack heterogeneity therefore, to supplement ground measurement networks, remotely sensed images of snow covered area (SCA) provide useful information for runoff prediction during the snowmelt season. SCA has been used as a direct input to hydrological models such as Snowmelt Runoff Model (SRM) or as a means of assimilating hydrologic model snowpack and checking the internal validity as in the case of HBV model. Alternative ways of handling melt water modeling using satellite derived SCA is discussed, with emphasis on the contrasting treatments in two widely used hydrologic models, SRM and HBV. The greatest similarity between the two models is that each uses a temperature index method to predict melt rate whereas the greatest difference lies in the way snow cover is handled. Moderate Resolution Imaging Spectroradiometer (MODIS) daily snow cover products with 500 m spatial resolution are used to derive SCA data in this study. Since the cloud obscuring problem degrades the use of satellites with optical sensors, a special combination and filtering methodology is utilized to reduce cloud coverage of the product. Both models are used to simulate runoff for the years 2001-2010 with model efficiency above 0.86 and volume difference less than 2.5%. Finally, operational snowmelt runoff forecasting is carried out for 2011 ablation season using numerical weather prediction (Mesoscale Model 5) data as forcing input variables. Discussion of results are supervised to reflect the general debates in hydrologic modeling in terms of parameters and calibration, internal validation, the value and limitations of using satellite derived and numerical weather prediction data. Key words: snow, SRM, HBV, forecasting, Upper Euphrates Basin

Sorman, A. A.; Sensoy, A.; Yamankurt, E.; Gozel, E.

2012-04-01

256

Autophagy and the (Pro)renin Receptor  

PubMed Central

The (pro)renin receptor (PRR) is a newly reported member of the renin-angiotensin system (RAS); a hormonal cascade responsible for regulating blood pressure. Originally, identification of PRR was heralded as the next drug target of the RAS, of which such therapies would have increased benefits against target-organ damage and hypertension. However, in the years since its discovery, several conditional knockout mouse models of PRR have demonstrated an essential role for this receptor unrelated to the RAS and blood pressure. Specific deletion of PRR in podocytes or cardiomyocytes resulted in the rapid onset of organ failure and subsequently animal mortality after only a matter of weeks. In both cell types, loss of PRR resulted in the intracellular accumulation of autophagosomes and misfolded proteins, indicating a disturbance in autophagy. In light of the fact that the majority of PRR is located intracellularly, this molecular function appears to be more relevant than its ability to bind to high, non-physiological concentrations of (pro)renin. This review will focus on the role of PRR in autophagy and its importance in maintaining cellular homeostasis. Understanding the link between PRR, autophagy and how its loss results in cell death will be essential for deciphering its role in physiology and pathology.

Binger, Katrina J.; Muller, Dominik N.

2013-01-01

257

Communicating stigma: the pro-ana paradox.  

PubMed

This study explores the personal experience of pro-ana bloggers, members of an online community for people with eating disorders. Using Erving Goffman's work on stigma, this study explores the motivations, benefits, and drawbacks of blogging about a stigmatized mental illness, as taken from the bloggers' own perceptive. We conducted 33 interviews with bloggers from seven different countries via phone, Skype, and e-mail. Participants were motivated to blog because they found social support, a way to cope with a stigmatized illness, and means of self-expression. Participants described blogging as a cathartic experience and perceived the social support they received from other members of the pro-ana community as a benefit. The fear that the eating disorder will be revealed if the blog is exposed and the concern that the blog encourages disordered eating were the perceived negative consequences of maintaining such a blog. Thus, blogging about anorexia serves to both alleviate and trigger anxiety about living with this stigmatized illness. Recommendations for future research are made. PMID:22873763

Yeshua-Katz, Daphna; Martins, Nicole

2013-01-01

258

Pro-Life, Pro-Woman? Frame Extension in the American Antiabortion Movement  

Microsoft Academic Search

This article argues that some leaders within the US antiabortion movement are pursuing a frame extension in order to attract new adherents to their cause. While the dominant rhetoric of the movement today focuses on the fetus and the immorality of abortion, pro-woman rhetoric has reemerged that leverages both the language of women's rights as well as science in order

Melody Rose

2011-01-01

259

Optimization and validation of FePro cell labeling method.  

PubMed

Current method to magnetically label cells using ferumoxides (Fe)-protamine (Pro) sulfate (FePro) is based on generating FePro complexes in a serum free media that are then incubated overnight with cells for the efficient labeling. However, this labeling technique requires long (>12-16 hours) incubation time and uses relatively high dose of Pro (5-6 microg/ml) that makes large extracellular FePro complexes. These complexes can be difficult to clean with simple cell washes and may create low signal intensity on T2* weighted MRI that is not desirable. The purpose of this study was to revise the current labeling method by using low dose of Pro and adding Fe and Pro directly to the cells before generating any FePro complexes. Human tumor glioma (U251) and human monocytic leukemia cell (THP-1) lines were used as model systems for attached and suspension cell types, respectively and dose dependent (Fe 25 to 100 microg/ml and Pro 0.75 to 3 microg/ml) and time dependent (2 to 48 h) labeling experiments were performed. Labeling efficiency and cell viability of these cells were assessed. Prussian blue staining revealed that more than 95% of cells were labeled. Intracellular iron concentration in U251 cells reached approximately 30-35 pg-iron/cell at 24 h when labeled with 100 microg/ml of Fe and 3 microg/ml of Pro. However, comparable labeling was observed after 4 h across the described FePro concentrations. Similarly, THP-1 cells achieved approximately 10 pg-iron/cell at 48 h when labeled with 100 microg/ml of Fe and 3 microg/ml of Pro. Again, comparable labeling was observed after 4 h for the described FePro concentrations. FePro labeling did not significantly affect cell viability. There was almost no extracellular FePro complexes observed after simple cell washes. To validate and to determine the effectiveness of the revised technique, human T-cells, human hematopoietic stem cells (hHSC), human bone marrow stromal cells (hMSC) and mouse neuronal stem cells (mNSC C17.2) were labeled. Labeling for 4 hours using 100 microg/ml of Fe and 3 microg/ml of Pro resulted in very efficient labeling of these cells, without impairing their viability and functional capability. The new technique with short incubation time using 100 microg/ml of Fe and 3 microg/ml of Pro is effective in labeling cells for cellular MRI. PMID:19517015

Janic, Branislava; Rad, Ali M; Jordan, Elaine K; Iskander, A S M; Ali, Md M; Varma, N Ravi S; Frank, Joseph A; Arbab, Ali S

2009-01-01

260

A novel TK-NOG based humanized mouse model for the study of HBV and HCV infections.  

PubMed

The immunodeficient mice transplanted with human hepatocytes are available for the study of the human hepatitis viruses. Recently, human hepatocytes were also successfully transplanted in herpes simplex virus type-1 thymidine kinase (TK)-NOG mice. In this study, we attempted to infect hepatitis virus in humanized TK-NOG mice and urokinase-type plasminogen activator-severe combined immunodeficiency (uPA-SCID) mice. TK-NOG mice were injected intraperitoneally with 6 mg/kg of ganciclovir (GCV), and transplanted with human hepatocytes. Humanized TK-NOG mice and uPA/SCID mice were injected with hepatitis B virus (HBV)- or hepatitis C virus (HCV)-positive human serum samples. Human hepatocyte repopulation index (RI) estimated from human serum albumin levels in TK-NOG mice correlated well with pre-transplantation serum ALT levels induced by ganciclovir treatment. All humanized TK-NOG and uPA-SCID mice injected with HBV infected serum developed viremia irrespective of lower replacement index. In contrast, establishment of HCV viremia was significantly more frequent in TK-NOG mice with low human hepatocyte RI (<70%) than uPA-SCID mice with similar RI. Frequency of mice spontaneously in early stage of viral infection experiment (8weeks after injection) was similar in both TK-NOG mice and uPA-SCID mice. Effects of drug treatment with entecavir or interferon were similar in both mouse models. TK-NOG mice thus useful for study of hepatitis virus virology and evaluation of anti-viral drugs. PMID:24140055

Kosaka, Keiichi; Hiraga, Nobuhiko; Imamura, Michio; Yoshimi, Satoshi; Murakami, Eisuke; Nakahara, Takashi; Honda, Yoji; Ono, Atsushi; Kawaoka, Tomokazu; Tsuge, Masataka; Abe, Hiromi; Hayes, C Nelson; Miki, Daiki; Aikata, Hiroshi; Ochi, Hidenori; Ishida, Yuji; Tateno, Chise; Yoshizato, Katsutoshi; Sasaki, Tamito; Chayama, Kazuaki

2013-11-01

261

Incidence of Liver Damage of Uncertain Origin in HIV Patients Not Co-Infected with HCV/HBV  

PubMed Central

Background and Aims Several studies have reported that a significant number of HIV patients not co-infected with HCV/HBV develop liver damage of uncertain origin (LDUO). The objective of our study was to evaluate the incidence of and risk factors for the development of LDUO in HIV infected patients not co-infected with HCV/HBV. Methods Prospective longitudinal study that included HIV-infected patients free of previous liver damage and viral hepatitis B or C co-infections. Patients were followed up at 6-monthly intervals. Liver stiffness was measured at each visit. Abnormal liver stiffness (ALS) was defined as a liver stiffness value greater than 7.2 kPa at two consecutive measurements. For patients who developed ALS, a protocol was followed to diagnose the cause of liver damage. Those patients who could not be diagnosed with any specific cause of liver disease were diagnosed as LDUO and liver biopsy was proposed. Results 210 patients matched the inclusion criteria and were included. 198 patients completed the study. After a median (Q1–Q3) follow-up of 18 (IQR 12–26) months, 21 patients (10.6%) developed ALS. Of these, fifteen patients were diagnosed as LDUO. The incidence of LDUO was 7.64 cases/100 patient-years. Histological studies were performed on ten (66.6%) patients and all showed liver steatosis. A higher HOMA-IR value and body mass index were independently associated with the development of LDUO. Conclusion We found a high incidence of LDUO in HIV-infected patients associated with metabolic risk factors. The leading cause of LDUO in our study was non-alcoholic fatty liver disease.

Rivero-Juarez, Antonio; Camacho, Angela; Merchante, Nicolas; Perez-Camacho, Ines; Macias, Juan; Ortiz-Garcia, Carmen; Cifuentes, Celia; Torre-Cisneros, Julian; Pena, Jose; Pineda, Juan A.; Rivero, Antonio

2013-01-01

262

Study of the expression levels of Hepatocyte nuclear factor 4 alpha and 3 beta in patients with different outcome of HBV infection  

PubMed Central

Hepatocyte nuclear factors 4 alpha (HNF4?) and 3 beta (HNF3?) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV) and liver inflammation. However, the relationship of the level of HNF4? and HNF3? with the severity of HBV-infected liver diseases is unclear. In this study, liver tissue samples from different types of HBV patients were collected, and HNF4? and HNF3? expression were detected by immunohistochemistry. The expression of HNF4? was significant higher in patients with severe hepatitis B(SHB) than those with chronic hepatitis B(CHB) and liver cirrhosis(LC) (both P < 0.05), but similar between patients with CHB and LC (P > 0.05). And the expression of HNF3? was similar among patients with CHB, LC and SHB (P > 0.05 for all pairwise comparison). This suggests that the expression level of HNF4? was different in patients with different outcome of HBV infection, high expression level of HNF4? may correlate with occurrence of SHB

2012-01-01

263

Virus NAT for HIV, HBV, and HCV in Post-Mortal Blood Specimens over 48 h after Death of Infected Patients - First Results  

PubMed Central

Summary Objective According to EU regulations (EU directive 2006/17/EC), blood specimens for virologic testing in the context of post-mortal tissue donation must be taken not later than 24 h post mortem. Methods To verify validity of NAT in blood specimens collected later, viral nucleic acid concentrations were monitored in blood samples of deceased persons infected with HIV (n = 7), HBV (n = 5), and HCV (n = 17) taken upon admission and at 12 h, 24 h, 36 h and 48 h post mortem. HIV and HCV RNA were quantified using Cobas TaqMan (Roche), HBV DNA was measured by in-house PCR. Results A more than 10-fold decrease of viral load in samples taken 36 h or 48 h post mortem was seen in one HIV-infected patient only. For all other patients tested the decrease of viral load in 36-hour or 48-hour post-mortal samples was less pronounced. Specimens of 3 HIV- and 2 HBV-infected patients taken 24 h post mortem or later were even found to have increased concentrations (>10-fold), possibly due to post-mortem liberation of virus from particular cells or tissues. Conclusion Our preliminary data indicate that the time point of blood collection for HIV, HBV and HCV testing by PCR may be extended to 36 h or even 48 h post mortem and thus improve availability of tissue donations.

Meyer, Thomas; Polywka, Susanne; Wulff, Birgit; Edler, Carolin; Schroder, Ann Sophie; Wilkemeyer, Ina; Kalus, Ulrich; Pruss, Axel

2012-01-01

264

Variants Identified by Hepatocellular Carcinoma and Chronic Hepatitis B Virus Infection Susceptibility GWAS Associated with Survival in HBV-Related Hepatocellular Carcinoma  

PubMed Central

Recent genome-wide association studies (GWAS) have identified several common susceptibility loci associated with the risk of hepatocellular carcinoma (HCC) or chronic hepatitis B infection (CHB). However, the relationship between these genetic variants and survival of patients with hepatitis B virus (HBV)-related HCC is still unknown. In this study, 22 single nucleotide polymorphisms (SNPs) were genotyped among 330 HBV-related HCC patients using the MassARRAY system from Sequenom. Cox proportional hazards regression was used to examine the effects of genotype on survival time under an additive model with age, sex, smoking status and clinical stage as covariates. We identified four SNPs on 6p21 (rs1419881 T>C, rs7453920 G>A,rs3997872 G>A and rs7768538 T>C), and two SNPs on 8p12 (rs2275959 C>T and rs7821974 C>T) significantly associated with survival time of HBV-related HCC patients. Our results suggest that HCC or CHB susceptibility loci might also affect the prognosis of patients with HBV-related HCC.

Zhao, Jianjun; Li, Zhiyu; Zhou, Jianguo; Zhang, Meng; Huang, Zhen; Zhao, Hong; Cai, Jianqiang

2014-01-01

265

HBV transmission from an occult carrier with five mutations in the major hydrophilic region of HBsAg to an immunosuppressed plasma recipient.  

PubMed

We describe the case of transmission of an HBsAg-negative hepatitis B infection to an immunosuppressed patient by plasma donation from an HBsAg-negative subject, but with very low serum HBV DNA (about 50 IU/ml) and five mutations in the major hydrophilic region of HBsAg. PMID:23856167

Coppola, Nicola; Loquercio, Giovanna; Tonziello, Gilda; Azzaro, Rosa; Pisaturo, Mariantonietta; Di Costanzo, Gaetano; Starace, Mario; Pasquale, Giuseppe; Cacciapuoti, Carmela; Petruzziello, Arnolfo

2013-09-01

266

Partially Randomized, Non-Blinded Trial of DNA and MVA Therapeutic Vaccines Based on Hepatitis B Virus Surface Protein for Chronic HBV Infection  

PubMed Central

Background Chronic HBV infects 350 million people causing cancer and liver failure. We aimed to assess the safety and efficacy of plasmid DNA (pSG2.HBs) vaccine, followed by recombinant modified vaccinia virus Ankara (MVA.HBs), encoding the surface antigen of HBV as therapy for chronic HBV. A secondary goal was to characterize the immune responses. Methods Firstly 32 HBV e antigen negative (eAg–) participants were randomly assigned to one of four groups: to receive vaccines alone, lamivudine (3TC) alone, both, or neither. Later 16 eAg+ volunteers in two groups received either 3TC alone or both 3TC and vaccines. Finally, 12 eAg– and 12 eAg+ subjects were enrolled into higher-dose treatment groups. Healthy but chronically HBV-infected males between the ages of 15 – 25 who lived in the western part of The Gambia were eligible. Participants in some groups received 1 mg or 2 mg of pSG2.HBs intramuscularly twice followed by 5×107 pfu or 1.5×108 pfu of MVA.HBs intradermally at 3-weekly intervals with or without concomitant 3TC for 11–14 weeks. Intradermal rabies vaccine was administered to a negative control group. Safety was assessed clinically and biochemically. The primary measure of efficacy was a quantitative PCR assay of plasma HBV. Immunity was assessed by IFN-? ELISpot and intracellular cytokine staining. Results Mild local and systemic adverse events were observed following the vaccines. A small shiny scar was observed in some cases after MVA.HBs. There were no significant changes in AST or ALT. HBeAg was lost in one participant in the higher-dose group. As expected, the 3TC therapy reduced viraemia levels during therapy, but the prime-boost vaccine regimen did not reduce the viraemia. The immune responses were variable. The majority of IFN-? was made by antigen non-specific CD16+ cells (both CD3+ and CD3–). Conclusions The vaccines were well tolerated but did not control HBV infection. Trial Registration ISRCTN ISRCTN67270384

Cavenaugh, James S.; Awi, Dorka; Mendy, Maimuna; Hill, Adrian V. S.; Whittle, Hilton; McConkey, Samuel J.

2011-01-01

267

A336C/A336T/T337C variations in HBV core gene and spontaneous hepatitis B e antigen loss in chronic hepatitis B patients  

PubMed Central

Background A336C/A336T/T337C variations in HBV core gene were demonstrated to relate to the decreases in serum HBV DNA levels and HBV replication in chronic hepatitis B patients. Usually the drastic decrease in serum HBV DNA levels correlates with spontaneous HBeAg loss during the course of chronic HBV infection. The aim of the present study was to investigate whether there was correlation between A336C/A336T/T337C variations and spontaneous HBeAg loss Methodology/Principal Findings A modified PCR-RFLP assay and ELISA were adopted to determine A336C/A336T/T337C variations and serum HBeAg levels in chronic hepatitis B patients without any antiviral therapy, respectively, whereas G1896A variation and HBV genotype were detected using Taqman-PCR assay. RFLP pattern C, E, G, C/G mixture and a new pattern C' were found in this study. A336C/A336T/T337C variations occurred in 40/166(24.1%) chronic hepatitis B patients. Chi-square test showed that C336/T336/C337 variants was more frequent in chronic hepatitis B patients with A1896 variants than those with the wild type G1896 (?2 = 4.7, P = 0.03), and moreover, patients with C336/T336/C337 variants had a significantly lower HBeAg-positive percentage than those with the wild type A336/T337. Binary logistic regression identified genotype B (OR = 4.1, 95%CI = 1.8-9.2, P = 0.001), the presence of C336/T336/C337 variants (OR = 3.2, 95%CI = 1.2-8.5, P = 0.02) and A1896 variants (OR = 7.8, 95%CI = 3.3-18.5, P < 0.001) as independent factors associated with spontaneous HBeAg loss. Conclusion/Significance A336C/A336T/T337C were naturally occurring polymorphisms in HBV core gene, and moreover, the presence of C336/T336/C337 variants was first demonstrated to be an independent factor associating with spontaneous HBeAg loss in chronic hepatitis B patients.

2011-01-01

268

A subset of Suz12/PRC2 target genes is activated during HBV replication and liver carcinogenesis associated with hepatitis B virus X protein  

PubMed Central

Chronic hepatitis B virus (HBV) infection is a major risk factor for developing liver cancer, and the HBV X protein (pX) has been implicated as a cofactor in hepatocyte transformation. We have shown that HBV replication as well as in vitro transformation by pX are associated with induction of the mitotic polo-like kinase 1 (Plk1) and down-regulation of the chromatin remodeling components Suz12 and Znf198. Herein, we demonstrate the same inverse relationship between Plk1 and Suz12/Znf198 in liver tumors from X/c-myc bitransgenic mice and woodchuck hepatitis virus (WHV)-infected woodchucks. Employing these animal models and the HBV replicating HepAD38 cells we examined the effect of Suz12/Znf198 down-regulation on gene expression. Genes analyzed include hepatic cancer stem cell markers BAMBI, DKK1,2, DLK1, EpCAM, MYC, and proliferation genes CCNA1, CCND2, IGFII, MCM4–6, PLK1, RPA2 and TYMS. Suz12 occupancy at the promoters of BAMBI, CCND2, DKK2, DLK1, EpCAM and IGFII was demonstrated by chromatin immunoprecipitation in untransformed hepatocytes, but was markedly reduced in pX-transformed and Suz12 knockdown cells. Accordingly, we refer to these genes as “Suz12 repressed” genes in untransformed hepatocytes. The Suz12 repressed genes and proliferation genes were induced in HBV-replicating HepAD38 cells, and interestingly, they exhibited distinct expression profiles during HCC progression in X/c-myc bitransgenics. Specifically, CCND2, EpCAM and IGFII expression was elevated at the proliferative and preneoplastic stages in X/c-myc bitransgenic livers, whereas BAMBI and PLK1 were over-expressed in hepatic tumors from X/c-myc bitransgenics and WHV-infected woodchucks. Importantly, most of these genes were selectively up-regulated in HBV-induced HCCs. Conclusion The distinct expression profile of the identified Suz12 repressed genes in combination with the proliferation genes hold promise as biomarkers for progression of chronic HBV infection to HCC.

Studach, Leo L.; Menne, Stephan; Cairo, Stefano; Buendia, Marie Annick; Hullinger, Ronald L.; Lefrancois, Lydie; Merle, Philippe; Andrisani, Ourania M.

2012-01-01

269

A computational approach to identify point mutations associated with occult hepatitis B: significant mutations affect coding regions but not regulative elements of HBV  

PubMed Central

Background Occult Hepatitis B Infection (OBI) is characterized by absence of serum HBsAg and persistence of HBV-DNA in liver tissue, with low to undetectable serum HBV-DNA. The mechanisms underlying OBI remain to be clarified. To evaluate if specific point mutations of HBV genome may be associated with OBI, we applied an approach based on bioinformatics analysis of complete genome HBV sequences. In addition, the feasibility of bioinformatics prediction models to classify HBV infections into OBI and non-OBI by molecular data was evaluated. Methods 41 OBI and 162 non-OBI complete genome sequences were retrieved from GenBank, aligned and subjected to univariable analysis including statistical evaluation. Their S coding region was analyzed for Stop codon mutations too, while S amino acid variability could be evaluated for genotype D only, due to the too small number of available complete genome OBI sequences from other genotypes. Prediction models were derived by multivariable analysis using Logistic Regression, Rule Induction and Random Forest approaches, with extra-sample error estimation by Multiple ten-fold Cross-Validation (MCV). Models were compared by t-test on the Area Under the Receiver Operating Characteristic curve (AUC) distributions obtained from the MCV runs for each model against the best-performing model. Results Variations in seven nucleotide positions were significantly associated with OBI, and occurred in 11 out of 41 OBI sequences (26.8%): likely, other mutations did not reach statistical significance due to the small size of OBI dataset. All variations affected at least one HBV coding region, but none of them mapped to regulative elements. All viral proteins, with the only exception of the X, were affected. Stop codons in the S, that might account for absence of serum HBsAg, were not significantly enriched in OBI sequences. In genotype D, amino acid variability in the S was higher in OBI than non-OBI, particularly in the immunodominant region. A Random Forest prediction model showed the best performance, but all models were not satisfactory in terms of specificity, due to the small sample size of OBIs; however results are promising in the perspective of a broader dataset of complete genome OBI sequences. Conclusions Data suggest that point mutations rarely occur in regulative elements of HBV, if ever, and contribute to OBI by affecting different viral proteins, suggesting heterogeneous mechanisms may be responsible for OBI, including, at least in genotype D, an escape mutation mechanism due to imperfect immune control. It appears possible to derive prediction models based on molecular data when a larger set of complete genome OBI sequences will become available.

2011-01-01

270

The representation of protein complexes in the Protein Ontology (PRO)  

PubMed Central

Background Representing species-specific proteins and protein complexes in ontologies that are both human- and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. Description We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. Conclusion PRO is a unique database resource for species-specific protein complexes. PRO facilitates robust annotation of variations in composition and function contexts for protein complexes within and between species.

2011-01-01

271

InterPro, progress and status in 2005  

PubMed Central

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).

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

272

French Pro/Am collaborations in exoplanet  

NASA Astrophysics Data System (ADS)

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.

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

273

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)

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.

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

2013-03-01

274

The Effect of HBV Genotype C on the Development of HCC Differs Between Wild-Type Viruses and Those With BCP Double Mutations (T1762A1764)  

PubMed Central

Background: Association of hepatitis B virus (HBV) genotype C with hepatocellular carcinoma (HCC) development remains controversial. HBV basal core promoter (BCP) double mutations (T1762A1764) are very strong confounding factors of genotypes B and C in HCC development. Objectives: To investigate the association of HBV genotype C with HCC development after controlling for BCP double mutations. Materials and methods: Four hundred and two serum samples from patients with HCC, liver cirrhosis (LC) and chronic hepatitis (CH) and also from asymptomatic HBsAg carriers were analyzed. Results: Genotypes B (31.1%), C (62.8%), and I (6.1%) were detected. With the severity of liver disease the prevalence of genotype B decreased, but genotype C increased. No trend was found for genotype I. The prevalence of BCP double mutations in genotypes C and I viruses was significantly higher than genotype B. BCP double mutations are risk factors for CH, LC and HCC. Genotype C was not identified as a particular risk factor for HCC prior to the stratification analysis but after that genotype C viruses with BCP double mutations were found to be a particular risk factor for HCC (P = 0.008, OR = 17.19 [95% CI: 2.10 - 140.41]), but those with the wild-type BCP were not. In the interaction analysis, genotype C and BCP double mutations were found to have a synergistic effect on HCC development (P < 0.0001, OR = 52.56 [95% CI: 11.49-240.52]). Conclusions: The effect of HBV genotype C on the development of HCC differs between wild-type viruses and those with BCP double mutations, suggesting that not all individuals infected with genotype C HBV are at increased risk of HCC.

Chen, Qin-Yan; Harrison, Tim J; Sabin, Caroline A; Li, Guo-Jian; Huang, Gao-Ming; Yang, Jin-Ye; Wang, Xue-Yan; Li, Hai; Liu, Mo-Han; Fang, Zhong-Liao

2014-01-01

275

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

PubMed Central

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.

2013-01-01

276

ProTherm and ProNIT: thermodynamic databases for proteins and protein-nucleic acid interactions  

PubMed Central

ProTherm and ProNIT are two thermodynamic databases that contain experimentally determined thermodynamic parameters of protein stability and protein–nucleic acid interactions, respectively. The current versions of both the databases have considerably increased the total number of entries and enhanced search interface with added new fields, improved search, display and sorting options. As on September 2005, ProTherm release 5.0 contains 17?113 entries from 771 proteins, retrieved from 1497 scientific articles (?20% increase in data from the previous version). ProNIT release 2.0 contains 4900 entries from 273 research articles, representing 158 proteins. Both databases can be queried using WWW interfaces. Both quick search and advanced search are provided on this web page to facilitate easy retrieval and display of the data from these databases. ProTherm is freely available online at and ProNIT at .

Kumar, M. D. Shaji; Bava, K. Abdulla; Gromiha, M. Michael; Prabakaran, Ponraj; Kitajima, Koji; Uedaira, Hatsuho; Sarai, Akinori

2006-01-01

277

Human tryptase cleaves pro-nerve growth factor (pro-NGF): hints of local, mast cell-dependent regulation of NGF/pro-NGF action.  

PubMed

Several factors regulate nerve growth factor (NGF), which is formed from pro-NGF by intracellular and extracellular enzymatic cleavage. The close proximity between mast cells expressing the protease tryptase and NGF-producing smooth muscle-like peritubular cells in the testes of infertile patients led us to examine whether tryptase is among those factors. Human peritubular cells express functional tryptase receptors (PAR-2). Recombinant enzymatically active ?-tryptase increased NGF levels in the culture medium of primary human peritubular cells, but the peptide agonist for PAR-2 (SLIGKV) did not. Neither tryptase nor the peptide increased NGF mRNA levels. To test whether the increase in NGF is due to enzymatic activity of tryptase acting on pro-NGF, supernatants of peritubular cells and synthetic pro-NGF were treated with tryptase. Results of Western blot studies indicate enzymatic cleavage of pro-NGF by active tryptase. Heat-inactivated tryptase or SLIGKV was not effective. Mass spectrometry analysis of in vitro cleavage products from recombinant tryptase and synthetic pro-NGF revealed multiple cleavage sites within the pro-NGF sequence. The results also indicate the generation of mature NGF and smaller NGF fragments as a result of tryptase action. Thus, tryptase-secreting mast cells in the vicinity of pro-NGF/NGF-secreting cells in any human tissue are likely able to alter the ratios of pro-NGF/NGF. As NGF and pro-NGF have different affinities for their receptors, this indicates a novel way by which mast cells, via tryptase, can modify the microenvironment in human tissues with regard to neurotrophin actions. PMID:21768088

Spinnler, Katrin; Fröhlich, Thomas; Arnold, Georg J; Kunz, Lars; Mayerhofer, Artur

2011-09-01

278

ProTherm and ProNIT: thermodynamic databases for proteins and protein-nucleic acid interactions  

Microsoft Academic Search

ProTherm and ProNIT are two thermodynamic data- bases that contain experimentally determined ther- 15 modynamic parameters of protein stability and protein-nucleic acid interactions, respectively. The current versions of both the databases have consid- erably increased the total number of entries and enhanced search interface with added new fields, 20 improved search, display and sorting options. As on September 2005, ProTherm

M. D. Shaji Kumar; K. Abdulla Bava; M. Michael Gromiha; Ponraj Prabakaran; Koji Kitajima; Hatsuho Uedaira; Akinori Sarai

2006-01-01

279

Pro-inflammatory and pro-Apoptotic Properties of Human Defensin 5  

PubMed Central

Defensins are cationic antimicrobial peptides that play an important role in innate immunity by primarily acting against microbes. Their antimicrobial properties have been widely studied and are well understood. Defensins contribute to regulation of host immunity also. Their effects on cells of the host however are less well understood. Here, we report on the pro-inflammatory and apoptotic properties of Human Defensin 5, the major antimicrobial peptide of ileal Paneth cells. We find that HD-5 up-regulates expression of genes involved in cell survival and inflammation in a NF-kB-dependent fashion in epithelial cells. Further, we find that HD-5 has pro-apoptotic effects on intestinal epithelial cells as well as primary CD4+ T cells.

Lu, Wuyuan; de Leeuw, Erik

2013-01-01

280

Pro-death and pro-survival properties of ouabain in U937 lymphoma derived cells  

PubMed Central

Background Epidemiological studies revealed significantly lower mortality rates in cancer patients receiving cardiac glycosides, which turned on interest in the anticancer properties of these drugs. However, cardiac glycosides have also been shown to stimulate cell growth in several cell types. In the present investigation we analyzed the pro-death and pro-survival properties of ouabain in the human lymphoma derived cell line U937. Methods ROS, intracellular Ca++, cell cycle were evaluated by loading the cells with fluorescent probes under cytofluorimetry. Cell counts and evaluation of trypan blue-excluding cells were performed under optic microscope. Protein detection was done by specific antibodies after protein separation from cellular lysates by SDS-PAGE and transfer blot. Results High doses of ouabain cause ROS generation, elevation of [Ca++]i and death of lymphoma derived U937 cells. Lower doses of OUA activate a survival pathway in which plays a role the Na+/Ca++-exchanger (NCX), active in the Ca++ influx mode rather than in the Ca++ efflux mode. Also p38 MAPK plays a pro-survival role. However, the activation of this MAPK does not appear to depend on NCX. Conclusion This investigation shows that the cardiac glycoside OUA is cytotoxic also for the lymphoma derived cell line U937 and that can activate a survival pathway in which are involved NCX and p38 MAPK. These molecules can represent potential targets of combined therapy.

2012-01-01

281

Ethical Dilemmas of Providing Pro Bono Art Therapy  

ERIC Educational Resources Information Center

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.

Moon, Bruce L.

2011-01-01

282

Pro-resolving lipid mediators are leads for resolution physiology.  

PubMed

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

Serhan, Charles N

2014-06-01

283

A comparison of SRM and HBV models for real time runoff forecasting in the Upper Euphrates Basin, Turkey  

NASA Astrophysics Data System (ADS)

Predicting snowmelt runoff in the mountainous eastern part of Turkey at a daily timescale is important in water resource management as it constitutes nearly 2/3 in volume of the total yearly runoff during spring and early summer months. Keeping track of snow dynamics and forecasting the amount and the timing of snowmelt runoff in the headwaters of the trans-boundary Euphrates River, where large dams are located, is a crucial and challenging task concerning the practical importance and great demand for real time forecasting of meltwater. In mountainous regions, data limitations prevent detailed understanding of the variability of snow cover and melt. In situ snowpack measurements are sparsely distributed relative to snowpack heterogeneity therefore to supplement ground measurement networks, remotely derived images of snow covered area (SCA) provides useful information for runoff prediction during the snowmelt season. SCA has been used as a direct input to hydrological models such as Snowmelt Runoff Model (SRM) or as a means of updating hydrologic model snowpack simulations and checking the internal validity of snowmelt runoff model as in the case of HBV model. Alternative ways of handling meltwater modeling using satellite derived SCA is discussed, with emphasis on the contrasting treatments in two widely used models, HBV and SRM. The greatest similarity between two models is that each uses a temperature index method to predict melt rate and the greatest difference between the models is in the way snow cover is handled. Moderate Resolution Imaging Spectroradiometer (MODIS) daily snow cover products with 500 m spatial resolution are used to derive SCA data in this study. Since the cloud obscuring problem degrades the use of satellites with optical sensors, a special combination and filtering methodology is used to reduce cloud coverage of the product. Both models are used to simulate runoff for the years 2003-2010 with model efficiency above 0.85 and volume difference around 2.5% and model parameters are calibrated in these applications. Finally, an operational snowmelt runoff forecasting is carried out for 2011 ablation season using numerical weather prediction Mesoscale Model 5 (MM5) data as forcing input variables. Discussion of results are supervised to reflect the general debates in hydrological modeling in terms of parameters and calibration, internal validation, the value and limitations of using satellite derived data.

Sorman, A.; Sensoy, A.; Gozel, E.; Yamankurt, E.; Sorman, U.

2011-12-01

284

Pro-inflammatory mediation of myoblast proliferation.  

PubMed

Skeletal muscle satellite cell function is largely dictated by the surrounding environment following injury. Immune cell infiltration dominates the extracellular space in the injured area, resulting in increased cytokine concentrations. While increased pro-inflammatory cytokine expression has been previously established in the first 3 days following injury, less is known about the time course of cytokine expression and the specific mechanisms of cytokine induced myoblast function. Therefore, the expression of IL-1? and IL-6 at several time points following injury, and their effects on myoblast proliferation, were examined. In order to do this, skeletal muscle was injured using barium chloride in mice and tissue was collected 1, 5, 10, and 28 days following injury. Mechanisms of cytokine induced proliferation were determined in cell culture using both primary and C2C12 myoblasts. It was found that there is a ?20-fold increase in IL-1? (p?0.05) and IL-6 (p?=?0.06) expression 5 days following injury. IL-1? increased proliferation of both primary and C2C12 cells ?25%. IL-1? stimulation also resulted in increased NF-?B activity, likely contributing to the increased proliferation. These data demonstrate for the first time that IL-1? alone can increase the mitogenic activity of primary skeletal muscle satellite cells and offer insight into the mechanisms dictating satellite cell function following injury. PMID:24647690

Otis, Jeffrey S; Niccoli, Sarah; Hawdon, Nicole; Sarvas, Jessica L; Frye, Melinda A; Chicco, Adam J; Lees, Simon J

2014-01-01

285

Pro-angiogenic properties of orosomucoid (ORM)  

SciTech Connect

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.

Irmak, Ster [Institute of Anatomy, University Hospital Essen, Hufelandstr. 55, D-45147 Essen (Germany)] [Institute of Anatomy, University Hospital Essen, Hufelandstr. 55, D-45147 Essen (Germany); Oliveira-Ferrer, Leticia [Department of Oncology/Hematology, University Hospital Hamburg-Eppendorf, Hamburg (Germany)] [Department of Oncology/Hematology, University Hospital Hamburg-Eppendorf, Hamburg (Germany); Singer, Bernhard B. [Institute of Anatomy, University Hospital Essen, Hufelandstr. 55, D-45147 Essen (Germany)] [Institute of Anatomy, University Hospital Essen, Hufelandstr. 55, D-45147 Essen (Germany); Erguen, Sueleyman, E-mail: sueleyman.erguen@uk-essen.de [Institute of Anatomy, University Hospital Essen, Hufelandstr. 55, D-45147 Essen (Germany)] [Institute of Anatomy, University Hospital Essen, Hufelandstr. 55, D-45147 Essen (Germany); Tilki, Derya [Department of Urology, University Hospital Grosshadern, Munich (Germany)] [Department of Urology, University Hospital Grosshadern, Munich (Germany)

2009-11-01

286

ProPortal: A Database for Prochlorococcus  

DOE Data Explorer

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.

Huang, Katherine [Chisholm lab, MIT

287

Pro-Inflammatory Mediation of Myoblast Proliferation  

PubMed Central

Skeletal muscle satellite cell function is largely dictated by the surrounding environment following injury. Immune cell infiltration dominates the extracellular space in the injured area, resulting in increased cytokine concentrations. While increased pro-inflammatory cytokine expression has been previously established in the first 3 days following injury, less is known about the time course of cytokine expression and the specific mechanisms of cytokine induced myoblast function. Therefore, the expression of IL-1? and IL-6 at several time points following injury, and their effects on myoblast proliferation, were examined. In order to do this, skeletal muscle was injured using barium chloride in mice and tissue was collected 1, 5, 10, and 28 days following injury. Mechanisms of cytokine induced proliferation were determined in cell culture using both primary and C2C12 myoblasts. It was found that there is a ?20-fold increase in IL-1? (p?0.05) and IL-6 (p?=?0.06) expression 5 days following injury. IL-1? increased proliferation of both primary and C2C12 cells ?25%. IL-1? stimulation also resulted in increased NF-?B activity, likely contributing to the increased proliferation. These data demonstrate for the first time that IL-1? alone can increase the mitogenic activity of primary skeletal muscle satellite cells and offer insight into the mechanisms dictating satellite cell function following injury.

Otis, Jeffrey S.; Niccoli, Sarah; Hawdon, Nicole; Sarvas, Jessica L.; Frye, Melinda A.; Chicco, Adam J.; Lees, Simon J.

2014-01-01

288

Test Reviews: Reynolds, C., & Voress, J. K. (2007). "Test of Memory and Learning: Second Edition." Austin, TX: PRO-ED  

ERIC Educational Resources Information Center

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…

Schmitt, Ara J.; Decker, Scott L.

2009-01-01

289

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

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…

Davis, Blair J.

2010-01-01

290

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

PubMed Central

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 (?2) 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?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 years age group. There was no statistically significant association between age or other socio-demographic risk factors and HBsAg status. Numerous risk factors for HBV acquisition exists in our settings, but amongst these, only a history of a contact with hepatitis B infection was found to be significantly associated with HBsAg positivity (OR 1.63, 95% C.I 1.15-2.30). Finally, the coinfection rate of HBV/HIV was 0.74%. Conclusion The prevalence of hepatitis B among pregnant women in Cameroon is high, and the pattern tends towards high infectivity and therefore increased risk of perinatal HBV transmission. These highlight the need to step up preventive efforts against hepatitis B infection and perinatal HBV transmission in our community.

2013-01-01

291

[Impact of an anti-hepatitis B virus (HBV) immunization program in patients undergoing dialysis in Havana, Cuba].  

PubMed

The follow-up of HBV markers in selected high infection risk populations, in patients from the hemodialysis and peritoneal dialysis services was used to assess the effectiveness of a special vaccination program. Viral infection markers were studied in prevalence cross sections of the whole population of patients, and also by recording the reports of clinical cases of hepatitis B occurred during that period in those groups of patients. The prevention program consisted of the vaccination of all patients negative to the viral markers and the indication of vaccination for the new cases during the period of the kidney disease, just before the start of the treatment at the hemodialysis unit; besides all the persons susceptible to infection that had already been included in the program, regardless of the stage of the disease. The results show the benefit of the vaccination in these patients, but it is more effective in the period before the treatment with dialysis where there is a lower possibility of being exposed to the virus and the immune system is still competent. Once the program was established, after a follow up o 6 years, there have been no reports of new cases of hepatitis B and the incidence of the disease has been declining. PMID:11155765

González-Griego, M; Pentón, E; Delgado, G; Pérez-Oliva, J; Ramos, V; Izquierdo, M; García, G; Levy, N; Cinza, Z; Valdivia, I; Trujillo, J; Delahanty, A

2000-12-01

292

Pro/con a precessional geodynamo  

NASA Astrophysics Data System (ADS)

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 common belief, often expressed explicitly, that precession is incapable of energizing a geodynamo, a la Loper. We will present a critique of Loper’s 1975 paper and briefly discuss the common practice and belief that the geodynamo must be energized by thermal and/or compositional driven convection (motion). We note here that there is no observational evidence for existence of thermal or compositional convection within the liquid core or for growth of the solid core. Although there has been considerable success in adapting data in thermal/compositional models to yield near realistic solutions, that does not constitute a proof that those models apply to the Earth. There is absolute observational evidence for mantle precession, an Earth feature that is unique, along with the Earth’s magnetic field, among the terrestrial planets. We argue that great difficulty experienced in analysis and computation of precessional flow is a major explanation for its absence in current models of the geodynamo.

Vanyo, J.

2003-04-01

293

[Analysis of the results of the HIV-1, HCV and HBV viral load of the SEIMC External Quality Control Program. Year 2011].  

PubMed

Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most important markers in the follow-up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of the results obtained by microbiology laboratories. This article summarizes the results of the 2011 SEIMC External Quality Control Program for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients in the range of 2-5 log10 copies/mL; to determine repeatability, two of these standards were identical. A significant proportion of the laboratories (52.1% on average) obtained values outside the accepted range (mean ± 0,25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was very good, with up to 94.9% of laboratories reporting results within the accepted range (?<0,5 log10 copies/ mL). The HBV and HCV program consisted of two standards with different viral load contents. In most of the participating laboratories (90% in the case of HCV and 86% in that of HBV), all the results were within the accepted range (mean ± 1.96 SD log10UI/mL). Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to the marked interlaboratory variability found, use of the same method and the same laboratory for patient follow-up is advisable. PMID:23453225

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

2013-02-01

294

Postoperative interferon ? treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial  

Microsoft Academic Search

Background\\/Aims: Recurrence after resection of hepatocellular carcinoma (HCC) is a frequent event. This study evaluated the effect of postoperative interferon ? (IFN ?) treatment on recurrence and survival in patients with hepatitis B virus (HBV)-related HCC. Method: Two hundred and thirty six patients were randomized after resection into IFN ? treatment (5 mu i.m. tiw for 18 months) and control groups. Treatment was

Hui-Chuan Sun; Zhao-You Tang; Lu Wang; Lun-Xiu Qin; Zeng-Chen Ma; Qin-Hai Ye; Bo-Heng Zhang; Yong-Bin Qian; Zhi-Quan Wu; Jia Fan; Xin-Da Zhou; Jian Zhou; Shuang-Jian Qiu; Yue-Fang Shen

2006-01-01

295

HIV replication is associated with increased severity of liver biopsy changes in HIV-HBV and HIV-HCV co-infection.  

PubMed

Histological parameters were assessed in liver biopsies (n?=?48) performed in patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and/or hepatitis C virus (HCV) in order to evaluate factors which were associated with significant liver disease. Necroinflammation and fibrosis was scored by the Ishak classification system, and binary logistic regression analysis was used to assess HIV and antiretroviral-related determinants of necroinflammation and fibrosis. A total of 46 biopsies were included; 33 were from HIV-positive patients co-infected with HCV and 15 biopsies were from HIV-positive patients co-infected with HBV. One HIV-positive patient was co-infected with HBV and HCV. Median biopsy inflammatory grade for the cohort was 8.5 (IQR 6-10), the median fibrosis Stage 2 (IQR 1.8-4), and the median steatosis score was 1 (IQR 0-2). At the univariate level, HIV-related variables that were significantly associated with more severe biopsy changes were higher HIV RNA at the time of biopsy (associated with inflammatory Grade 10+; P?=?0.018) and any exposure to didanasine (ddI) or stavudine (D4T; associated with fibrosis Stage 3+; P?=?0.022). HIV RNA at the time of biopsy remained significant at the multivariate level. Patients with HIV hepatitis co-infection in this cohort had surprisingly mild changes in liver histology, and there were no statistically significant differences between biopsy results in HBV compared to HCV co-infection. The association between HIV RNA and necroinflammation supports current recommendations for earlier initiation of HAART in patients with HIV-hepatitis co-infection. PMID:22585714

Audsley, Jennifer; du Cros, Philipp; Goodman, Zachary; McLean, Catriona; Mijch, Anne; Lewin, Sharon R; Sasadeusz, Joe

2012-07-01

296

Abnormal functional connectivity within the default mode network in patients with HBV-related cirrhosis without hepatic encephalopathy revealed by resting-state functional MRI.  

PubMed

By means of "task free" resting-state functional magnetic resonance imaging (rs-fMRI), abnormal functional connectivity (FC) of the default mode network (DMN) in cirrhotic patients with hepatic encephalopathy (HE) has been reported; however, little is known about the changes of DMN in cirrhotic patients without overt or minimal HE. The aim of this study was to investigate whether there was a disruption of the FC within the DMN in patients with hepatitis B virus (HBV)-related cirrhosis without any signs of HE. Fifty one patients with HBV-related cirrhosis without HE and 61 age- and gender-matched healthy controls underwent the rs-fMRI. Seed-based region-to-region FC was used to analyze the connectivity between each pair of regions within the DMN, including posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), hippocampal formation (HF), inferior parietal cortex (IPC), and medial temporal lobe (MTL). Pearson correlation analysis was performed between the abnormal FC strength within the DMN and venous blood ammonia levels in patients. Compared with the controls, patients with HBV-related cirrhosis without HE demonstrated significantly decreased region-to-region FC between the mPFC and bilateral MTL, right HF, and left IPC, as well as between the right MTL and left IPC, right HF, and PCC. A significant negative relationship was observed between blood ammonia levels and connectivity strength between the mPFC and left IPC in patients. These results suggest that patients with HBV-related cirrhosis without HE had disrupted functional connectivty within the DMN, even before the appearance of minimal HE. PMID:24907446

Qi, Rongfeng; Zhang, Long Jiang; Xu, Qiang; Liang, Xue; Luo, Song; Zhang, Zhiqiang; Huang, Wei; Zheng, Ling; Lu, Guang Ming

2014-08-12

297

On-treatment monitoring of HBV DNA levels: predicting response and resistance to oral antiviral therapy at week 24 versus week 48  

Microsoft Academic Search

The suppression of hepatitis B viral (HBV) load correlates with favorable histologic, biochemical, and serologic responses\\u000a in clinical trials of patients with chronic hepatitis B (CHB). The ability to identify patients who will not experience durable\\u000a viral suppression in response to a specific antiviral regimen affords the opportunity for early treatment modification to\\u000a optimize outcomes and avoid the development of

Ting-Tsung Chang

2009-01-01

298

ProMoT: modular modeling for systems biology  

PubMed Central

Summary: The modeling tool ProMoT facilitates the efficient and comprehensible setup and editing of modular models coupled with customizable visual representations. Since its last major publication in 2003, ProMoT has gained new functionality in particular support of logical models, efficient editing, visual exploration, model validation and support for SBML. Availability: ProMoT is an open source project and freely available at http://www.mpi-magdeburg.mpg.de/projects/promot/. Contact: mirschel@mpi-magdeburg.mpg.de; mirschel@mpi-magdeburg.mpg.de Supplementary information: Supplementary data are available at Bioinformatics online.

Mirschel, Sebastian; Steinmetz, Katrin; Rempel, Michael; Ginkel, Martin; Gilles, Ernst Dieter

2009-01-01

299

Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients  

PubMed Central

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 ?-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.

EL-SAGHIRE, HOUSSEIN; VANDEVOORDE, CHARLOT; OST, PIET; MONSIEURS, PIETER; MICHAUX, ARLETTE; DE MEERLEER, GERT; BAATOUT, SARAH; THIERENS, HUBERT

2014-01-01

300

A hepatitis A, B, C and HIV prevalence and risk factor study in ever injecting and non-injecting drug users in Luxembourg associated with HAV and HBV immunisations  

Microsoft Academic Search

Background  In Luxembourg, viral hepatitis and HIV infection data in problem drug users (PDUs) are primarily based on self-reporting.\\u000a Our study aimed to determine the prevalence of HAV, HBV, HCV and HIV infections in ever injecting (IDUs) and non-injecting\\u000a drug users (nIDUs) including inherent risk factors analysis for IDUs. Secondary objectives were immunisation against HAV and\\u000a HBV, referral to care and

Nathalie Removille; Alain Origer; Sophie Couffignal; Michel Vaillant; Jean-Claude Schmit; Marie-Lise Lair

2011-01-01

301

Neither Diabetes Mellitus nor Overweight Is a Risk Factor for Hepatocellular Carcinoma in a Dual HBV and HCV Endemic Area: Community Cross-Sectional and Case–Control Studies  

Microsoft Academic Search

OBJECTIVES:Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are well-known risk factors for hepatocellular carcinoma, and diabetes mellitus (DM) and overweight have also been reported as risk factors for hepatocellular carcinoma (HCC). We tried to elucidate the roles of DM and overweight in HCC development in a dual HBV and HCV endemic area of southern Taiwan.METHODS:In 2004,

Hung-Da Tung; Jing-Houng Wang; Po-Lin Tseng; Chao-Hung Hung; Kwong-Ming Kee; Chien-Hung Chen; Kuo-Chin Chang; Chuan-Mo Lee; Chi-Sin Changchien; Yao-Der Chen; Sheng-Nan Lu

2010-01-01

302

ProDom and ProDom-CG: tools for protein domain analysis and whole genome comparisons  

Microsoft Academic Search

ProDom contains all protein domain families auto- matically generated from the SWISS-PROT and TrEMBL sequence databases (http:\\/\\/www.toulouse. inra.fr\\/prodom.html ). ProDom-CG results from a similar domain analysis as applied to completed genomes (http:\\/\\/www.toulouse.inra.fr\\/prodomCG.html ). Recent improvements to the ProDom database and its server include: scaling up to include sequences from TrEMBL, addition of Pfam-A entries to the set of expert validated

Florence Corpet; Florence Servant; Jérôme Gouzy; Daniel Kahn

2000-01-01

303

PRO-Detroit: A Pragmatic Approach to School Desegregation  

ERIC Educational Resources Information Center

The efforts of the Parents and Responsible Organizations for Detroit (PRO-Detroit) committee as a coordinating and umbrella group promoting peaceful compliance with court-ordered busing for desegregation are described. (MJB)

Straus, Kathleen; Schrager, Scott

1978-01-01

304

Prevalence of HBV and HCV among the multi-transfused beta thalassemic major patients in a day care centre of blood transfusion department of Mymensingh Medical College Hospital.  

PubMed

Though regular blood transfusion improves the overall survival of patients with ?-thalassemia which is one of the most common genetic diseases in the world, carries a definite risk of infection with blood-borne viruses. It is a major health problem, brings much morbidity, early mortality and a great deal of misery for a family both financially and emotionally. World Health Organization (WHO) reported that there is about 3% beta thalassemia carrier and more than two thousand thalassemic children are born every year in Bangladesh. We carried out this study to provide epidemiologic data on hepatitis B virus (HBV) & hepatitis C virus (HCV) infection among ?-thalassemic patients. Moreover, HBV & HCV infection-associated risk factors were investigated in this study. Two hundred patients with ?-thalassemia major were enrolled in this study. Using Rapid Immuno-chromatographic Test and their sera were tested for HBsAg and HCVAb. The positive HBsAg & HCVAb results were confirmed by ELISA. The study sample 200 consisted of 165 males (82.5%) and 35 females (17.5%), with a mean±SD age of 5.9±9.0 years. Four (2%) patients were HCV-Ab positive; 13(6.5%) were HBsAg positive. Univariate analysis showed that (P=0.01), older age (P=0.001), longer transfusion duration (P=0.000), HBsAg seropositivity (P=0.03), and higher serum ferritin level (P=0.002) were significantly associated with a higher prevalence of HCV. Using multivariate analysis, age (P<0.001), serum ferritin level (P< 0.001) were independent factors associated with HCV infection. Improvement of the people's knowledge about TTI risk factors, blood screening strategies and HBV vaccination have led to a dramatically decrease in prevalence of TTIs particularly HBV during the last decades in Bangladesh.However, post-transfusion transmission of HCV has still remained a major health concern in multi-transfused patients. As the prevalence of HCV infection is much higher among ?-thalassemic patients as compared with HBV infections routine screening of donated blood for HCV is highly recommended by ELISA. PMID:24858148

Chakrabarty, P; Rudra, S; Hossain, M A

2014-04-01

305

Processing of proSAAS in neuroendocrine cell lines.  

PubMed Central

ProSAAS, a recently discovered granin-like protein, potently inhibits prohormone convertase (PC)1, and might also perform additional functions. In the present study, the processing of proSAAS was compared in two neuroendocrine cell lines overexpressing this protein: the AtT-20 mouse pituitary corticotrophic line and the PC12 rat adrenal phaeochromocytoma line. The processing of proSAAS was examined by pulse-chase analysis using [(3)H]leucine, by MS, and by chromatography and radioimmunoassay. Various smaller forms of proSAAS were detected, including peptides designated as little SAAS, PEN and big LEN. Because the PC-12 cells used in the present study do not express either PC1 or PC2, the finding that these cells efficiently cleave proSAAS indicates that these cleavages do not require either enzyme. Two of the peptides identified in AtT-20 media represent novel C-terminally truncated forms of PEN. In both cell lines, the secretion of the small proSAAS-derived peptides is stimulated by secretagogues. However, long-term treatment of wild-type AtT-20 cells with two different secretagogues (8-bromo-cAMP and a phorbol ester) does not affect levels of proSAAS mRNA; this treatment significantly increases PC1 mRNA by approx. 60-80%. The lack of co-regulation of proSAAS and PC1 mRNA implies that enzyme activity can be induced without an accompanying increase in the inhibitor. In addition, the finding that the peptides are secreted via the regulated pathway is consistent with the proposal that they may function as neuropeptides.

Mzhavia, Nino; Qian, Yimei; Feng, Yun; Che, Fa-Yun; Devi, Lakshmi A; Fricker, Lloyd D

2002-01-01

306

ProCAT: a data analysis approach for protein microarrays  

PubMed Central

Protein microarrays provide a versatile method for the analysis of many protein biochemical activities. Existing DNA microarray analytical methods do not translate to protein microarrays due to differences between the technologies. Here we report a new approach, ProCAT, which corrects for background bias and spatial artifacts, identifies significant signals, filters nonspecific spots, and normalizes the resulting signal to protein abundance. ProCAT provides a powerful and flexible new approach for analyzing many types of protein microarrays.

Zhu, Xiaowei; Gerstein, Mark; Snyder, Michael

2006-01-01

307

InterPro: the integrative protein signature database.  

PubMed

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

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

308

Propulsive Small Expendable Deployer System (ProSEDS)  

NASA Technical Reports Server (NTRS)

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.

1999-01-01

309

The survival of the pro-choice movement.  

PubMed

In the US, the pro-choice movement has not only survived but grown stronger in the 25 years since the legalization of abortion provided its greatest victory. This longevity is explained through an examination of the internal organizational changes which have taken place in the movement as well as the external changes which have taken place in the political environment surrounding the movement. After providing a theoretical basis for this investigation, the history of the pro-choice movement in the US is traced in light of these elements. In the pre-1973 era, the movement lacked formal organization but was bolstered by external political factors provided by the protest cycle of the 1960s. During 1973-76, the actions of anti-abortion groups forced pro-choice groups to develop the more formalized organizational structures which helped the pro-choice movement survive its initial success and the decline of the era of protests. In the period 1976-83, the anti-abortion movement achieved passage of the Hyde Amendment banning federal funding of abortions. This victory by the opposition led to an expansion in the pro-choice movement which included the formation of many local reproductive rights organizations. Many of these organizations failed to create formalized structures and, therefore, failed to maintain their impetus to survive. However, NARAL (the National Association for Repeal of Abortion Laws) had adopted a more formalized structure and professional leadership following the Hyde legislation and developed strong, formal connections with its state affiliates while continuing to strengthen grassroots actions. The visible threats to abortion laws mounted by the anti-abortion groups added to NARAL's strength. During 1983-89, the pro-choice movement gained some key victories which threatened its survival. Continued activity on the part of the anti-abortion groups (such as release of the movie "The Silent Scream") generated enough pro-choice support, however, to weather this period. The activities of Operation Rescue also stimulated pro-choice reactions. In the period 1989-92, the Supreme Court gave pro-choice groups a victory in its Webster vs. Reproductive Health decision. Thus, NARAL's membership grew to an unprecedented 400,000 in 1990 and allowed the group to pump money into local grassroots activities. By the time the Court issued its Casey decision in 1992, neither group was willing to claim victory, although the ruling was a great victory for pro-choice forces because although the Court allowed states to impose new restrictions to abortion, it refused to overturn Roe vs. Wade. 1992 also saw the election of a pro-choice President who was able to appoint a pro-choice Justice to the Supreme Court in 1993. The ability of the pro-choice movement to survive victory (the creation of a favorable political opportunity structure) will be decided by the critical battles surrounding attempts to limit access to abortion providers as well as the accessibility of drug-induced abortion. State legislatures will remain major battlefields because of the Court-allowed restrictions. The pro-choice movement will also have to resolve conflicts over strategy such as whether to appeal to mainstream Americans or use the favorable climate to push for rights. The pro-choice movement will likely survive because the anti-abortion groups continue to pose threats and because formal organizations with professional leadership will keep the issues before the membership. PMID:12346343

Staggenborg, S

1995-01-01

310

Nod1, a CARD protein, enhances pro-interleukin-1? processing through the interaction with pro-caspase-1  

Microsoft Academic Search

The production of bioactive interleukin-1? (IL-1?), a pro-inflammatory cytokine, is mediated by activated caspase-1. One of the known molecular mechanisms underlying pro-caspase-1 processing and activation involves interaction between the caspase recruit domains (CARDs) of caspase-1 and a serine\\/threonine kinase RIP2. While the association of Nod1 with both caspase-1 and RIP2 is already known, the consequences of these interactions are poorly

Nam Jin Yoo; Won Sang Park; Su Young Kim; John C Reed; Seong Gon Son; Jung Young Lee; Sug Hyung Lee

2002-01-01

311

The InterPro BioMart: federated query and web service access to the InterPro Resource.  

PubMed

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

Jones, Philip; Binns, David; McMenamin, Conor; McAnulla, Craig; Hunter, Sarah

2011-01-01

312

Synthesis, DNA recognition and cleavage studies of novel tetrapeptide complexes, Cu(II)/Zn(II)-Ala-Pro-Ala-Pro  

NASA Astrophysics Data System (ADS)

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.

Arjmand, Farukh; Jamsheera, A.; Mohapatra, D. K.

2013-05-01

313

Propulsive Small Expendable Deployer System (ProSEDS)  

NASA Technical Reports Server (NTRS)

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.

Ballance, Judy; Johnson, Les; Rogacki, John R. (Technical Monitor)

2000-01-01

314

Propulsive Small Expendable Deployer System (ProSEDS)  

NASA Astrophysics Data System (ADS)

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 (5-km bare wire plus 10-km spectra or dyneema) from a Delta II second stage to achieve ~0.4 N 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 upperstage 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. .

Ballance, Judy; Johnson, Les

2001-02-01

315

ProServer: a simple, extensible Perl DAS server  

PubMed Central

Summary: The increasing size and complexity of biological databases has led to a growing trend to federate rather than duplicate them. In order to share data between federated databases, protocols for the exchange mechanism must be developed. One such data exchange protocol that is widely used is the Distributed Annotation System (DAS). For example, DAS has enabled small experimental groups to integrate their data into the Ensembl genome browser. We have developed ProServer, a simple, lightweight, Perl-based DAS server that does not depend on a separate HTTP server. The ProServer package is easily extensible, allowing data to be served from almost any underlying data model. Recent additions to the DAS protocol have enabled both structure and alignment (sequence and structural) data to be exchanged. ProServer allows both of these data types to be served. Availability: ProServer can be downloaded from http://www.sanger.ac.uk/proserver/ or CPAN http://search.cpan.org/~rpettett/. Details on the system requirements and installation of ProServer can be found at http://www.sanger.ac.uk/proserver/. Contact: rmp@sanger.ac.uk Supplementary Materials: DasClientExamples.pdf

Finn, Robert D.; Stalker, James W.; Jackson, David K.; Kulesha, Eugene; Clements, Jody; Pettett, Roger

2007-01-01

316

A Phase II, Randomized Study on an Investigational DTPw-HBV/Hib-MenAC Conjugate Vaccine Administered to Infants in Northern Ghana  

PubMed Central

Background Combining meningococcal vaccination with routine immunization in infancy may reduce the burden of meningococcal meningitis, especially in the meningitis belt of Africa. We have evaluated the immunogenicity, persistence of immune response, immune memory and safety of an investigational DTPw-HBV/Hib-MenAC conjugate vaccine given to infants in Northern Ghana. Methods and Findings In this phase II, double blind, randomized, controlled study, 280 infants were primed with DTPw-HBV/Hib-MenAC or DTPw-HBV/Hib vaccines at 6, 10 and 14 weeks of age. At 12 months of age, children in each group received a challenge dose of serogroup A+C polysaccharides. Antibody responses were assessed pre, and one month-post dose 3 of the priming schedule and pre and 1 month after administration of the challenge dose. One month post-dose 3, 87.8% and 88.2% of subjects in the study group had bactericidal meningococcal serogroup A (SBA-MenA) and meningococcal serogroup C (SBA-MenC) antibody titres ?1?8 respectively. Seroprotection/seropositivity rates to the 5 antigens administered in the routine EPI schedule were non-inferior in children in the study group compared to those in the control group. The percentages of subjects in the study group with persisting SBA-MenA titres ? 1?8 or SBA-MenC titres ?1?8 at the age of 12 months prior to challenge were significantly higher than in control group (47.7% vs 25.7% and 56.4% vs 5.1% respectively). The administration of 10 ?g of serogroup A polysaccharide increased the SBA-MenA GMT by 14.0-fold in the DTPW-HBV/HibMenAC-group compared to a 3.8 fold increase in the control-group. Corresponding fold-increases in SBA-MenC titres following challenge with 10 ?g of group C polysaccharide were 18.8 and 1.9 respectively. Reactogenicity following primary vaccination or the administration of the challenge dose was similar in both groups, except for swelling (Grade 3) after primary vaccination which was more frequent in children in the vaccine than in the control group (23.7%; 95%CI [19.6–28.1] of doses vs 14.1%; 95% CI [10.9–17.8] of doses). Fifty-nine SAEs (including 8 deaths), none of them related to vaccination, were reported during the entire study. Conclusions Three dose primary vaccination with DTPw-HBV/Hib-MenAC was non-inferior to DTPw-HBV/Hib for the 5 common antigens used in the routine EPI schedule and induced bactericidal antibodies against Neisseria meningitidis of serogroups A and C in the majority of infants. Serogroup A and C bactericidal antibody levels had fallen below titres associated with protection in nearly half of the infants by the age of 12 months confirming that a booster dose is required at about that age. An enhanced memory response was shown after polysaccharide challenge. This vaccine could provide protection against 7 important childhood diseases (including meningococcal A and C) and be of particular value in countries of the African meningitis belt. Trial Registration Controlled-Trials.com ISRCTN35754083

Hodgson, Abraham; Forgor, Abudulai Adams; Chandramohan, Daniel; Reed, Zarifah; Binka, Fred; Bevilacqua, Cornelia; Boutriau, Dominique; Greenwood, Brian

2008-01-01

317

Interferon signal transduction of biphenyl dimethyl dicarboxylate/amantadine and anti-HBV activity in HepG2 2.2.15.  

PubMed

Biphenyl dimethyl dicarboxylate (DDB) is a hepatoprotectant, which is used as an adjuvant agent in a treatment for chronic hepatitis. Amantadine is an antiviral agent, which is utilized primarily in the treatment of influenza, but also, occasionally in the treatment of hepatitis C. In a previous study, we reported that DDB, coupled with amantadine, would exert an anti-HBV effect, via the induction of interferon-inducible gene expression in the HepG2 2.2.15 cell line. The primary objective of the present study was to determine whether or not DDB and/or amantadine exhibit anti-HBV properties, and what mechanisms of action might be involved in such properties. In our study, we were able to determine that DDB stimulates Jak/Stat signaling, and induces the expression of interferon alpha (IFN-alpha) stimulated genes, most notably 6-16 and ISG12. In addition, the antiviral effectors induced by IFN-alpha, PKR, OAS, and MxA, were regulated in the presence of DDB at its optimal concentration (250 microg/mL), to a degree commensurate with the degree of induction associated with the IFN-alpha treated group. Finally, we determined that the replication of pregenomic RNA and HBeAg was inhibited by DDB treatment, and this inhibition was maximized when coupled with the administration of amantadine (25 microg/mL). In conclusion, the results of this study demonstrated clearly that DDB, as well as the combination of DDB/amantadine, directly inhibited IFN-alpha signaling-mediated replication of HBV in infected hepatocytes, and thus may represent a novel treatment for chronic hepatitis B, which would be characterized principally by its improved safety over other treatment strategies. PMID:16756086

Joo, Seong Soo; Won, Tae Joon; Kim, Min Jung; Hwang, Kwang Woo; Lee, Do Ik

2006-05-01

318

Blockade of B7-H1 enhances dendritic cell-mediated T cell response and antiviral immunity in HBV transgenic mice.  

PubMed

Dendritic cells (DCs) have been identified as the most effective antigen-presenting cell (APC), much attention has been directed toward the use of DCs in vaccine strategies for the treatment of cancer or chronic virus infection. B7-H1 (PD-L1) is a ligand for programmed cell death-1 (PD-1) and does not bind to other CD28 family members, it is expressed on resting and upregulated on activated B, T, myeloid, and dendritic cells (DCs). The overwhelming number of studies supports the role of B7-H1 as a negative regulator of T cell responses. RNA interference (RNAi) is a mechanism for sequence-specific posttranscriptional inhibition of gene expression via double stranded RNA molecules and it has recently been applied to mammalian cells with the use of small interfering RNAs (siRNAs). In the study, transfection of DCs with siRNA specific for B7-H1 gene resulted in the blockade of the expression of B7-H1 on DCs. The allostimulatory activity of DCs could be enhanced by silencing of B7-H1 on DCs. Blockade of B7-H1 on DCs inhibited the production of IFN-? and IL-10 but not IL-2 and IL-4 in mixed lymphocyte reaction (MLR). HBV specific peptide-pulsed DCs could break tolerance and trigger specific CTL responses, the level of HBsAg and HBV DNA in sera of HBV transgenic mice decreased, whereas blockade of B7-H1 on DCs augmented the effects. These data strongly support the concept that blockade of B7-H1 can enhance DC-mediated antiviral immune responses. PMID:22133510

Jiang, Wenzheng

2012-01-17

319

Motoneuron Programmed Cell Death in Response to proBDNF  

PubMed Central

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.

Taylor, AR; Gifondorwa, DJ; Robinson, MB; Strupe, JL; Prevette, D; Johnson, JE; Hempstead, BL; Oppenheim, RW; Milligan, CE

2011-01-01

320

Presence of pro-tobacco messages on the Web.  

PubMed

Ignored in the finalized Master Settlement Agreement (National Association of Attorneys General, 1998), the unmonitored, unregulated World Wide Web (Web) can operate as a major vehicle for delivering pro-tobacco messages, images, and products to millions of young consumers. A content analysis of 318 randomly sampled pro-tobacco Web sites revealed that tobacco has a pervasive presence on the Web, especially on e-commerce sites and sites featuring hobbies, recreation, and "fetishes." Products can be ordered online on nearly 50% of the sites, but only 23% of the sites included underage verification. Further, only 11% of these sites contain health warnings. Instead, pro-tobacco sites frequently associate smoking with "glamorous" and "alternative" lifestyles, and with images of young males and young (thin, attractive) females. Finally, many of the Web sites offered interactive site features that are potentially appealing to young Web users. Recommendations for future research and counterstrategies are discussed. PMID:12356288

Hong, Traci; Cody, Michael J

2002-01-01

321

ProCure21+ should speed scheme starts.  

PubMed

This October saw the launch of the new ProCure21+ National Framework under which, the Department of Health (DH) team behind the new scheme claims, the NHS can potentially save a further pound 200 million of public money on top of the substantial sums saved under predecessor, ProCure21, via faster, more streamlined procurement, design, planning, and construction, of publicly-funded healthcare schemes. HEJ editor Jonathan Baillie discussed, with the DH's senior responsible officer (SRO) and P21+ team leader Peter Sellars, the background to the new Framework's introduction, the success of its forerunner, and the additional benefits that ProCure21 + (which is backed by organisations incuding HM Treasury, the National Audit Office, and the Office of Government Commerce) should bring to the entire healthcare building supply chain. PMID:21141235

Baillie, Jonathan

2010-11-01

322

Tapasin modification on the intracellular epitope HBcAg18-27 enhances HBV-specific CTL immune response and inhibits hepatitis B virus replication in vivo.  

PubMed

HBV-specific cytotoxic T-lymphocyte (CTL) activity has a very important role in hepatitis B virus clearance. Present studies suggest that Tapasin, a endoplasmic reticulum (ER) chaperone, stabilizes the peptide-receptive MHC I conformation, allowing peptide exchange and increasing more peptides to be translocated into the ER. We have previously testified that cytoplasmic transduction peptide (CTP)-HBcAg18-27-Tapasin fusion protein could enter cytoplasm of dendritic cells, and enhance T cells' response to generate specific CTLs efficiently in vitro. In the present study, we evaluated specific immune responses of CTP-HBcAg18-27-Tapasin fusion protein in HLA-A2 transgenic mice (H-2K(b)) and anti-viral ability in HBV transgenic mice, and explored the mechanisms probably involved in. The studies showed that CTP-HBcAg18-27-Tapasin not only increased production of cytokine IFN-? and interleukin-2 (IL-2), compared with CTP-HBcAg18-27, HBcAg18-27-Tapasin, and PBS, but also significantly induced the higher percentages of IFN-?+CD8(+) T cells and specific CTL responses in HLA-A2 transgenic mice. Moreover, enhancement of specific CTL activity induced by the fusion protein reduced HBV DNA and hepatitis B surface antigen (HBsAg) levels and decreased the expression of HBsAg and hepatitis B core antigen (HBcAg) in liver tissue of HBV transgenic mice. In addition, CTP-HBcAg18-27-Tapasin could upregulate the expression of JAK2, Tyk2, STAT1, and STAT4 in T lymphocytes in HLA-A2 transgenic mice splenocytes. However, there was no significant difference on the expressions of JAK1, JAK3, and STAT6 between each group. In conclusion, CTP-HBcAg18-27-Tapasin fusion protein could enhance not only the percentages of CTLs but also induce robust specific CTL activity and inhibits hepatitis B virus replication in vivo, which was associated with activation of the JAK/STAT signaling pathway. PMID:24614195

Chen, Xiaohua; Tang, Yuyan; Zhang, Yi; Zhuo, Meng; Tang, Zhenghao; Yu, Yongsheng; Zang, Guoqing

2014-05-01

323

Trefoil factor family peptide 2 acts pro-proliferative and pro-apoptotic in the murine retina.  

PubMed

Although expression of trefoil factor family (TFF) peptides has been reported in the brain, nothing is known about TFF expression in the retina. The aim of this study was to test whether TFF peptides are expressed in the murine retina and have any function here. In contrast to most tissues studied, where TFF1 and TFF3 are the predominant peptides, TFF2 is the only peptide expressed in the murine retina. Immunohistochemical studies on murine retinal sections indicate that cells of the ganglion cell layer are the retinal source for murine TFF2 (Tff2). In organotypic murine retina cell cultures recombinant TFF2 exerted a strong pro-apoptotic and pro-proliferative rather than an anti-apoptotic and anti-proliferating effect described in most human cancer cell lines investigated so far. In blockage experiments we were able to demonstrate that the pro-apoptotic effect of TFF2 is caspase-dependent. Western blot analysis of TFF2 treated retinal wholemount homogenates revealed significant reductions in the phosphorylation level of ERK and STAT3 proteins compared to basal conditions, suggesting that in the developing murine retina survival mechanism are down-regulated upon TFF2 administration. Our results suggest that during retinal cell death periods, requiring a tightly regulated balance between cell survival and cell death, TFF2 acts pro-proliferative and pro-apoptotic at least in developing mouse retinae cultured in vivo. PMID:21512811

Paunel-Görgülü, Adnana N; Franke, Andreas G; Paulsen, Friedrich P; Dünker, Nicole

2011-05-01

324

Two-dimensional 13C NMR study of the substance P fragment Arg?Pro?Lys?Pro  

NASA Astrophysics Data System (ADS)

The N-terminal Substance P fragment Arg 1?Pro 2?Lys 3?Pro 4 (SP 1-4) has been studied by means of natural abundance 13C NMR. By the combined application of various two-dimensional {13C}/{1H} correlation techniques, all 13C resonances in both isomeric forms (cis and trans about the Lys 3?Pro 4 peptide bond) including the quaternary carbons could be assigned unambiguously. The experimental details are outlined and the results are discussed in terms of the peptide conformation. From the data it can be concluded that the cis-SP 1-4 is stabilized by a charge interaction between the end group of the Lys 3 side chain and the deprotonated carboxyl group at the C-terminal end of the peptide. A ring-like interaction with the Arg 1 residue can be excluded. Some 13C? 1H long-range coupling constant have also been measured.

Otter, Albin; Kotovych, George

325

Trends in risk of transfusion-transmitted viral infections (HIV, HCV, HBV) in France between 1992 and 2003 and impact of nucleic acid testing (NAT).  

PubMed

Monitoring trends in residual risk of transfusion-transmitted viral infections is important to assess improvements in blood safety and to adapt the risk reduction policies. These trends were analysed in France over 4 periods of 3 years (1992-1994, 1995-1997, 1998-2000 and 2001-2003). The 2001-2003 estimates were compared to the results of HIV-1 and HCV NAT implemented on all blood donations in July 2001. Due to improvements in donor recruitment and selection, continuing progress in screening assays, and preventive measures taken in the community to control infections, a significant decrease was observed in residual risks for HIV, HCV and HBV between 1992 and 2003. The residual risk is currently extremely low: for the 2001-2003 period, this risk was estimated at 1 in 3.15 million donations for HIV, at 1 in 10 million for HCV and at 1 in 640,000 for HBV. Of the 6.14 million donations screened with NAT between July 2001 and December 2003 in France, 2 HIV-positive and 3 HCV-positive donations were discarded thanks to NAT, representing a yield of 1 in 3.07 million for HIV and 1 in 2.05 million for HCV. These results show the limited benefit of NAT and suggest that its cost-effectiveness is poor. PMID:15735313

Pillonel, J; Laperche, S

2005-02-01

326

Detection of EBV, HBV, HCV, HIV-1, HTLV-I and -II, and SMRV in Human and Other Primate Cell Lines  

PubMed Central

The high prevalence of contaminated cell cultures suggests that viral contaminations might be distributed among cultures. We investigated more than 460 primate cell lines for Epstein-Barr (EBV), hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus type 1 (HIV-1), human T-cell leukemia/lymphoma virus I and II (HTLV-I/-II), and squirrel monkey retrovirus (SMRV) infections for risk assessment. None of the cell lines were infected with HCV, HIV-1, or HTLV-I/-II. However, one cell line displayed reverse transcriptase activity. Thirty-nine cell lines harbored EBV DNA sequences. Studies on the lytic phase of EBV revealed that five cell lines produce EBV particles and six further cell lines produced EBV upon stimulation. One cell line contained an integrated HBV genome fragment but showed no virus production. Six cell lines were SMRV-infected. Newly established cell lines should be tested for EBV infections to detect B-lymphoblastoid cell lines (B-LCL). B-LCLs established with EBV from cell line B95-8 should be tested for SMRV infections.

Uphoff, Cord C.; Denkmann, Sabine A.; Steube, Klaus G.; Drexler, Hans G.

2010-01-01

327

A Genetic Variant in the Promoter Region of miR-106b-25 Cluster Predict Clinical Outcome of HBV-Related Hepatocellular Carcinoma in Chinese  

PubMed Central

Background MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response, tumorigenesis and progression. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7. Our previous study showed that the A to G base change of rs999885 may provide an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. However, it is unknown whether rs999885 is associated with prognosis of intermediate or advanced HBV-related hepatocellular carcinoma (HCC) patients. Methods The SNP, rs999885, was genotyped by using the TaqMan allelic discrimination Assay in 414 intermediate or advanced HCC patients. Log-rank test and Cox proportional hazard models were used for survival analysis. Results The variant genotypes of rs999885 were associated with a significantly decreased risk of death for intermediate or advanced HCC [additive model: adjusted hazard ratio (HR) ?=?0.76,95% confidence intervals (CI) ?=?0.59–0.97]. Further stepwise regression analysis suggested that rs999885 was an independently protective factor for the prognosis of HCC in the final model (additive model: adjusted HR ?=?0.72, 95% CI ?=?0.56–0.91, P?=?0.007). Conclusions These findings indicate that the A to G base change of rs999885 may provide a protective effect on the prognosis of intermediate or advanced HCC in Chinese.

Pan, Yun; Liu, Yao; Liu, Jibin; Wen, Juan; Xie, Kaipeng; Shen, Hongbing; Ma, Hongxia; Miao, Yi; Hu, Zhibin

2014-01-01

328

Two versus three doses of a meningococcal C conjugate vaccine concomitantly administered with a hexavalent DTaP-IPV-HBV/Hib vaccine in healthy infants.  

PubMed

The immunogenicity and reactogenicity of a meningococcal serogroup C (MenC) conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib vaccine according to a two- or three-dose schedule in healthy infants was evaluated. At 1 month post-vaccination, 98% (two doses) and 100% (three doses) of subjects had serum bactericidal antibody using human complement assay (hSBA) titres > or =1:8; at 12 months of age > or =89% of subjects in each group remained seroprotected. Induction of immunological memory, as evaluated by administration of a meningococcal serogroup A/C polysaccharide vaccine challenge dose, was similar for both regimens and no interference was observed in the immune response to MenC or hepatitis B virus antigens. Reactogenicity was similar in each group. MenC conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib to healthy infants in the first year of life using a two-dose schedule is as safe and immunogenic as a three-dose regimen. PMID:18407386

Schmitt, Heinz-J; Steul, Katrin Simone; Borkowski, Astrid; Ceddia, Francesca; Ypma, Ellen; Knuf, Markus

2008-04-24

329

A study on the biochemical and the morphological changes in the liver in renal transplant recipients with an evidence of the HBV and the HCV infections.  

PubMed

Context: Renal transplantation is the definitive treatment in renal failure patients. Liver disease is a known problem in renal transplant recipients. They may be consequent to immunosuppression, drug toxicity, altered immune response to viruses and hemodialysis.Aims: The aim of this study was to analyze and correlate the biochemical parameters and histopathology of liver biopsy among renal transplant recipients with both HBV and HCV infection and to correlate them.Setting: The study group had thirty cases. Enrolment criteria included coinfection with HBV and HCV ; elevated liver enzymes and recipient of renal allograft. There was acontrol group of ten patients who were HBC and HCV positive but had not undergone renal transplant.Material & Methods: Liver function tests including alkaline phosphatase, SGOT, SGPT and serum bilirubin levels were donet. Percutaneous liver biopsies were carried out using Menghini's needle.. Stains done included hematoxylin and eosin (H & E), vanGieson, reticulin and Perl's stain. Histopathological grading was performed using Metavir scoring system. Immunohistochemistry (IHC) was done where required for ground glass hepatocytes. Correlation of SGOT, SGPT and Alkaline phosphatase of the study group and the controls was carried out with the grading.Statistical Analysis: Statistical tests done included paired "t" test at 5% and test of probability.Results: There was no statistically significant correlation between the controls and the transplanted patients. It was concluded that serum enzyme levels could be used to predict histological grade in the control group but not in the transplant recipients (p>0.05). PMID:23450682

Sharma, Sonia; Gupta, Anshu; Kalhan, Shivani; Dudani, Sharmila; Sharma, Pankaj; Devra, Amit

2013-01-01

330

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)

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.

Cannon, A. J.

2006-12-01

331

Are Vertical Restraints Pro? or Anticompetitive? Lessons from Interstate Circuit  

Microsoft Academic Search

At the heart of antitrust law is the prohibition on horizontal collusion. To enforce this prohibition, the law must accurately define what collusion entails. One of the most con- troversial areas in antitrust is the issue of vertical restraints. In the last 20 years, economists have come up with any number of pro- and anticompetitive rationales for such restraints. Given

2001-01-01

332

Are Vertical Restraints Pro or Anticompetitive? Lessons from Interstate Circuit  

Microsoft Academic Search

At the heart of antitrust law is the prohibition on horizontal collusion. To enforce this prohibition, the law must accurately define what collusion entails. One of the most controversial areas in antitrust is the issue of vertical restraints. In the last 20 years, economists have come up with any number of pro- and anticompetitive rationales for such restraints. Given this,

David A Butz; Andrew N Kleit

2001-01-01

333

Development of Pro-Peptide Immunotherapy for Breast Cancer.  

National Technical Information Service (NTIS)

The proposed study will test the hypothesis that solid tumors can be eliminated by immunizing the host with specific foreign peptides and by delivering these peptides to the tumors in the form of pro-peptides which are activated at the tumor sites. This i...

W. Wei

2003-01-01

334

PRO development: rigorous qualitative research as the crucial foundation  

PubMed Central

Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity.

Marquis, Patrick; Vigneux, Marc; Abetz, Linda; Arnould, Benoit; Bayliss, Martha; Crawford, Bruce; Rosa, Kathleen

2010-01-01

335

Mexican American Adolescents' Perceptions of a Pro-College Culture  

ERIC Educational Resources Information Center

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…

Castillo, Linda G.; Conoley, Collie W.; Cepeda, Lisa M.; Ivy, Karen K.; Archuleta, Debra J.

2010-01-01

336

Engineering Graphics/Pro-Engineer on the Web  

NSDL National Science Digital Library

This website, authored by Stephen W. Crown of the University of Texas-Pan American, is the 1999 recipient of Premier Award for Excellence in Engineering Education Courseware. It includes a course syllabus for an Engineering Graphics course, virtual world, lecture notes, games and quizzes, class photos, and pro-engineer tutorials.

Crown, Stephen W.

2009-07-24

337

Virtex-II Pro SEE Test Methods and Results.  

National Technical Information Service (NTIS)

The objective of this coarse Single Event Effect (SEE) test is to determine the suitability of the corrrmezcial Virtex-11 Pro family for use in spaceflight applications. To this end, this test is primarily intended to determine any Singe Event Latchup (SE...

D. Paetrick W. Powell

2005-01-01

338

Hydrated silicas modified by nonsilane pro-adhesion compounds  

Microsoft Academic Search

The surface modification of hydrated silicas, precipitated from a solution of sodium metasilicate and gaseous carbon dioxide, was carried out. The modification was conducted in three ways (modification with evaporation of the solvent, heating of the silica-modifying compound solution system in a reflux condenser, and surface modification in a vacuum evaporator), using various amounts of pro-adhesion compounds, dissolved in organic

Andrzej Krysztafkiewicz; Bozena Rager

1999-01-01

339

Pro Football 97: Sports Illustrated Presents a Preseason Preview  

NSDL National Science Digital Library

The Cable News Network and Sports Illustrated have combined their formidable news gathering, analytic, and photographic talents to provide this site as an enhancement to the CNNSI TV network. A highlight of the site is a selection of articles from Sports Illustrated's Pro Football '97 Preview.

1997-01-01

340

Virtex-II Pro SEE Test Methods and Results.  

National Technical Information Service (NTIS)

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 app...

D. Petrick W. Powell J. Howard

2004-01-01

341

Memory for Pro-Social Intentions: When Competing Motives Collide  

ERIC Educational Resources Information Center

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…

Brandimonte, Maria A.; Ferrante, Donatella; Bianco, Carmela; Villani, Maria Grazia

2010-01-01

342

Propulsive Small Expendable Deployer System (ProSEDS)  

NASA Technical Reports Server (NTRS)

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.

1999-01-01

343

Virtex-II Pro SEE Test Methods and Results  

NASA Technical Reports Server (NTRS)

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.

Petrick, David; Powell, Wesley; Howard, James W., Jr.; LaBel, Kenneth A.

2004-01-01

344

Potent antioxidant dendrimers lacking pro-oxidant activity.  

PubMed

It is well known that antioxidants have protective effects against oxidative stress. Unfortunately, in the presence of transition metals, antioxidants, including polyphenols with potent antioxidant activities, may also exhibit pro-oxidant effects, which may irreversibly damage DNA. Therefore, antioxidants with strong free radical-scavenging abilities and devoid of pro-oxidant effects would be of immense biological importance. We report two antioxidant dendrimers with a surface rich in multiple phenolic hydroxyl groups, benzylic hydrogens, and electron-donating ring substituents that contribute to their potent free radical-quenching properties. To minimize their pro-oxidant effects, the dendrimers were designed with a metal-chelating tris(2-aminoethyl)amine (TREN) core. The dendritic antioxidants were prepared by attachment of six syringaldehyde or vanillin molecules to TREN by reductive amination. They exhibited potent radical-scavenging properties: 5 times stronger than quercetin and 15 times more potent than Trolox according to the 1,1-diphenyl-2-picrylhydrazyl assay. The antioxidant dendrimers also protected low-density lipoprotein, lysozyme, and DNA against 2,2'-azobis(2-amidinopropane) dihydrochloride-induced free radical damage. More importantly, unlike quercetin and Trolox, the two TREN antioxidant dendrimers did not damage DNA via their pro-oxidant effects when incubated with physiological amounts of copper ions. The dendrimers also showed no cytotoxicity toward Chinese hamster ovary cells. PMID:20977937

Lee, Choon Young; Sharma, Ajit; Uzarski, Rebecca L; Cheong, Jae Eun; Xu, Hao; Held, Rich A; Upadhaya, Samik K; Nelson, Julie L

2011-04-15

345

Psychological Antecedents of Heterosexuals' Pro-gay Activism Behavior  

Microsoft Academic Search

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

Wayne W. Wilkinson; Brad J. Sagarin

2010-01-01

346

Cervical arthroplasty using ProDisc-C Case Report  

PubMed Central

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.

Nica, DA; Copaciu, R

2013-01-01

347

Pro-resolving lipid mediators and diabetic wound healing  

PubMed Central

Purpose of Review Defective wound healing is one of the most prominent clinical manifestations of both type 1 and type 2 diabetes. As the global rates of diabetes increase, a detailed understanding of the molecular and cellular defects that give rise to unresolved inflammation and delayed wound healing in diabetes is urgently required. Emerging evidence indicates that timely resolution of inflammation is mediated in part by endogenous pro-resolving lipid mediators, such as resolvins. Here, we review recent advances in the area of resolution and diabetes and highlight the potential of novel pro-resolving strategies for promoting wound healing in diabetes. Recent Findings Macrophage dysfunction is a critical underlying feature of altered wound healing in diabetic patients. This is associated with defective clearance of apoptotic cells, increased risk of infection and altered angiogenesis. Diabetes and obesity are associated with chronic inflammation and altered biosynthesis of bioactive lipid mediators that promote the resolution of inflammation. Stimulating resolution with pro-resolving lipid mediators improves metabolic parameters in diabetes, blunts systemic inflammation, restores defective macrophage phagocytosis and accelerates wound healing in animal models of obesity and diabetes. Summary Stimulating resolution with pro-resolving lipid mediators may represent a novel strategy for promoting wound healing in diabetes.

Hellmann, Jason; Tang, Yunan; Spite, Matthew

2014-01-01

348

PRO development: rigorous qualitative research as the crucial foundation.  

PubMed

Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity. PMID:20512662

Lasch, Kathryn Eilene; Marquis, Patrick; Vigneux, Marc; Abetz, Linda; Arnould, Benoit; Bayliss, Martha; Crawford, Bruce; Rosa, Kathleen

2010-10-01

349

Using Pro/ENGINEER's(reg sign) interface module.  

National Technical Information Service (NTIS)

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 cap...

J. Schulze

1994-01-01

350

LNG Plant Optimization Tool CryoPro: A Joint Venture.  

National Technical Information Service (NTIS)

A base-load LNG plant is planned for the 'Snohvit' field in northern Norway. A design optimization tool, CryoPro, was developed by Statoil R&D and the Division of Refrigeration Engineering, NTH-SINTEF, to be used in concept evaluations. The conditions in ...

G. Owren E. Brendeng R. S. Heiersted A. Fredheim

1992-01-01

351

Review of the ProSEDS Electrodynamic Tether Mission Development  

NASA Technical Reports Server (NTRS)

The Propulsive Small Expendable Deployer System (ProSEDS) space experiment was ready to fly as a secondary payload on a Delta-II expendable launch vehicle in late March 2003. Concerns raised in February 2003 by the International Space Station resulted in the delay of the launch of ProSEDS. Issues associated with the delayed launch date and a change in starting altitude resulted in the cancellation of the mission. ProSEDS was intended to deploy a tether (5 km bare wire plus 10 km non-conducting Dyneema) from a Delta I1 second stage to achieve adequate drag thrust that would lower the orbit of the system over days as opposed to months due to atmospheric drag. It was also designed to utilize the tether-generated current to provide limited spacecraft power. Considerable effort and testing went in to developing the ProSEDS system by a dedicated team. Through this effort, important technological issues were identified and addressed and this presentation will discuss some of the important technical issues and hurdles that had to be addressed to successfully prepare for flight. It is intended that this information will be of use for future tether mission and experiment designers.

Vaughn, Jason A.; Curtis, Leslie; Gilchrist, Brian E.; Bilen, Sven; Lorenzini, Enrico

2004-01-01

352

Alterations of natriuretic peptides amino-terminal pro B-type natriuretic peptide and amino-terminal pro C-type natriuretic peptide during the pregnancy.  

PubMed

Abstract Objective: The aim of this study was to determine the plasma levels of natriuretic peptides amino-terminal pro B-type natriuretic peptide (NT proBNP) and amino-terminal pro C-type natriuretic peptide (NT proCNP) during pregnancy and any possible changes occurring in each trimester. Methods: This was a prospective longitudinal case-control study conducted in a University Hospital antenatal outpatient clinic. Subjects were all healthy pregnant women without a history of previous cardiac disease, hypertension or preeclampsia, and each patient was assessed during every trimester, and blood samples were collected for the measurement of NT proBNP and NT proCNP levels. Results: Twenty pregnant women were followed-up during pregnancy without any complications. We obtained longitudinal levels of natriuretic peptides in each trimester. The mean NT proBNP levels were 14.95?±?16.8, 9.37?±?10.76, 52.48?±?126.65?pmol/ml and the mean NT proCNP levels were 44.64?±?41.64, 45.70?±?47.03, 47.22?±?55.09?pmol/l, respectively. No statistically significant alteration of plasma levels of natriuretic peptides was detected between trimesters. Conclusion: This is the first study evaluating the longitudinal levels of NT proCNP during the pregnancy, and demonstrates that NT proCNP remained constant, but NT proBNP levels do not significantly alter during pregnancy. PMID:24090090

Tekin, Ye?im Bayo?lu; Güven, Emine Seda Güvenda?; K?rba?, Aynur; Cobano?lu, U?ur; Colak, Sabri; Do?an, Osman Deniz; Sahin, Figen Kir

2014-07-01

353

Development of Polymer Coatings for the ProSEDS Tether  

NASA Technical Reports Server (NTRS)

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.

Vaughn, Jason A.; Kamenetsky, Rachel R.; Finckenor, Miria; Wright, Ken

2000-01-01

354

Propulsive Small Expendable Deployer System (ProSEDS)  

NASA Technical Reports Server (NTRS)

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 11 Expendable Launch Vehicle second stage. ProSEDS, which is planned on an Air Force GPS Satellite replacement mission in June 2002, will use the flight proven Small Expendable Deployer System (SEDS) to deploy a tether (5 km bare wire plus 10 km non-conducting Dyneema) from a Delta 11 second stage to achieve approx. 0.4N drag thrust. ProSEDS will utilize the tether-generated current to provide limited spacecraft power. The ProSEDS instrumentation includes Langmuir probes and Differential Ion Flux Probes, 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 removal 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.

Curtis, Leslie; Johnson, Les; Brown, Norman S. (Technical Monitor)

2002-01-01

355

Evaluation of the Abbott RealTime HBV DNA Assay and Comparison to the Cobas AmpliPrep/Cobas TaqMan 48 Assay in Monitoring Patients with Chronic Cases of Hepatitis B?  

PubMed Central

The new Abbott RealTime hepatitis B virus (HBV) assay was compared to the Cobas AmpliPrep/Cobas TaqMan assay with 128 serum samples from patients with chronic hepatitis B. There was an excellent correlation (r = 0.961) between the two assays, with the Abbott RealTime test showing at least equivalent sensitivity and a slightly wider dynamic range than the Cobas TaqMan assay. By coupling high sensitivity with a large dynamic range, the Abbott RealTime HBV assay is useful in monitoring the response to antiviral therapy.

Ciotti, Marco; Marcuccilli, Fabbio; Guenci, Tania; Prignano, Maria Grazia; Perno, Carlo Federico

2008-01-01

356

Evaluation of the Abbott RealTime HBV DNA assay and comparison to the Cobas AmpliPrep/Cobas TaqMan 48 assay in monitoring patients with chronic cases of hepatitis B.  

PubMed

The new Abbott RealTime hepatitis B virus (HBV) assay was compared to the Cobas AmpliPrep/Cobas TaqMan assay with 128 serum samples from patients with chronic hepatitis B. There was an excellent correlation (r = 0.961) between the two assays, with the Abbott RealTime test showing at least equivalent sensitivity and a slightly wider dynamic range than the Cobas TaqMan assay. By coupling high sensitivity with a large dynamic range, the Abbott RealTime HBV assay is useful in monitoring the response to antiviral therapy. PMID:18272717

Ciotti, Marco; Marcuccilli, Fabbio; Guenci, Tania; Prignano, Maria Grazia; Perno, Carlo Federico

2008-04-01

357

A hepatitis A, B, C and HIV prevalence and risk factor study in ever injecting and non-injecting drug users in Luxembourg associated with HAV and HBV immunisations  

PubMed Central

Background In Luxembourg, viral hepatitis and HIV infection data in problem drug users (PDUs) are primarily based on self-reporting. Our study aimed to determine the prevalence of HAV, HBV, HCV and HIV infections in ever injecting (IDUs) and non-injecting drug users (nIDUs) including inherent risk factors analysis for IDUs. Secondary objectives were immunisation against HAV and HBV, referral to care and treatment facilities as well as reduction in risk behaviour. Methods A nationwide, cross-sectional multi-site survey, involving 5 in-, 8 out-treatment and 2 prison centres, included both an assisted questionnaire (n = 368) and serological detection of HIV and Hepatitis A, B, C (n = 334). A response rate of 31% resulted in the participation of 310 IDUs and 58 nIDUs. Risk factors such as drug use, sexual behaviour, imprisonment, protection and health knowledge (HAV, HBV status and immunisations, HCV, HIV), piercing/tattoo and use of social and medical services were studied by means of chi2 and logistic models. Results Seroprevalence results for IDUs were 81.3% (218/268, 95%CI=[76.6; 86.0]) for HCV, 29.1% (74/254, 95%CI=[25.5;34.7 ]) for HBV (acute/chronic infection or past cured infection), 2.5% (5/202, 95%CI=[0.3; 4.6]) for HIV-1 and 57.1% (108/189, 95%CI=[50.0; 64.1]) for HAV (cured infections or past vaccinations). Seroprevalence results for nIDUs were 19.1% (9/47, 95%CI=[7.9;30.3]) for HCV, 8.9% (4/45, 95%CI=[0.6;17.2]) for HBV (acute/chronic infection or past cured infection), 4.8% (2/42, 95%CI=[-1.7;11.3]) for HIV-1 and 65.9% (27/41, 95%CI=[51.4;80.4]) for HAV. Prisoners showed the highest rates for all infections. Age, imprisonment and setting of recruitment were statistically associated with HCV seropositivity. Age, speedball career and nationality were significantly associated with HBV seropositivity. Only 56% of the participants in outpatient centres collected their serology results and 43 doses of vaccine against HAV and/or HBV were administered. Conclusions Despite the existing national risk-reduction strategies implemented since 1993, high prevalence of HCV and HBV infections in injecting drug users is observed. Our study showed that implementing risk-prevention strategies, including immunisation remains difficult with PDUs. Improvement should be looked for by the provision of field healthcare structures providing tests with immediate results, advice, immunisation or treatment if appropriate.

2011-01-01

358

The increase of serum Bcl-2 concentration in moderate head injury outcome: The role of ACTH4-10Pro8-Gly9-Pro10  

PubMed Central

Background: Traumatic brain injury (TBI) is one of the major causes of death and disability. Apoptosis after TBI contributes significantly to the final extent of tissue damage. The Bcl-2 family proteins are important apoptosis modulators which increased in injured neurons. Bcl-2 has shown an antiapoptotic effect in rats and mice. ACTH4-10Pro8-Gly9-Pro10 is a synthetic short fragment of ACTH devoid of hormonal effects and has neuromodulatory properties. ACTH4-10Pro8-Gly9-Pro10 has been shown to increase levels of Bcl-2 and BDNF in vitro as well as in vivo. It has been postulated that ACTH4-10Pro8-Gly9-Pro10 will result in improved clinical outcome and reduce hospital length of stay. The goal of this study is to compare the effect of standard therapy only with standard therapy and ACTH4-10Pro8-Gly9-Pro10, the increase of Bcl-2, and clinical outcome with reduction of hospital stay. Materials and Methods: Subjects of moderate head injury (MHI) with no indication of surgery were taken consecutively (n = 40) and separated into two groups: standard treatment only and standard treatment combined with ACTH4-10Pro8-Gly9-Pro10. Blood samples were taken on day 1 and day 5 from each subject for measurements of Bcl-2 concentration. Barthel Index and MMSE were measured, at discharge and hospital length of stay was noted. Results: Forty subjects have been involved in this study, three subjects died in the standard therapy group, and one subject in ACTH4-10Pro8-Gly9-Pro10 group. Bcl-2 serum level in standard therapy was 1.39 ± 0.75 ng/mL on day 1 and 1.48 ± 0.77 ng/mL on day 5. After treatment with ACTH4-10Pro8-Gly9-Pro10, Bcl-2 level was 1.39 ± 0.70 ng/mL on day 1 and 3.70 ± 1.02 ng/mL on day 5. The serum Bcl-2 concentration was significantly increased with ACTH4-10Pro8-Gly9-Pro10 therapy with shorter hospital length of stay (P < 0.05). Conclusion: ACTH4-10Pro8-Gly9-Pro10 increased serum Bcl-2 levels and reduced hospital length of stay significantly compared with standard therapy alone.

Indharty, Rr Suzy

2013-01-01

359

[Effect of HBV on the expression of SREBP in the hepatocyte of chronic hepatitis B patients combined with hepatic fatty change].  

PubMed

To investigate the effect of HBV on the expression of Sterol regulatory element binding proteins( SREBP ) in the hepatocyte of patients with chronic hepatitis B (CHB) combined with hepatic fatty change. 55 cases diagnosed as CHB combined with hepatic fatty change in our department were selected and liver biopsies were carried out. The patients were dividied into 3 groups, group A: HBV DNA is less than or equal to 1000 copies/ml(15 cases), group B: 1000 copies/ml less than HBV DNA less than 100000 copies/ml (18 cases) and group C: HBV DNA is more than or equal to 100000 copies/ml (22 cases). 10 patients with HBV DNA in less than or equal to 1000 copies/ml after antiviral therapy with Nucleoside analogues were seen as group C1 (before treatment) and group C2 (after treatment) respectively; 12 patients with HBV DNA is more than or equal to 100000 copies/ml after antiviral therapy were classified as group C3 (before treatment) and group C4 (after treatment). Lipid droplets in the hepatic tissue were observed with oil red staining. Real time PCR were performed to detect the expressions of SREBP-1c and SREBP-2 mRNA in the liver. The protein expressions of SREBP-1c and SREBP-2 were detected with immunohistochemistry staining. Statistic data were analysed with SPSS11.5 software. (1) Red integrated optical densities (IOD) reflected by lipid drops in group A, B and C are 1004.27+/-218.63, 1937.01+/-401.47 and 4133.79+/-389.28 respectively, the degree of oil red O in each group was different (F = 385.69, P is less than to 0.01), which is increased as HBV DNA load increasing; Red IOD in group C1, C2 and C3, C4 are 4020.84+/-326.64, 1012.02+/-244.89, 4189.18+/-329.21 and 4121.76+/-304.09 respectively. Compared with group C1, the degree of oil red O in group C2 is decreased and the difference is statistically significant (t = 22.55, P is less than to 0.01); However, the difference of the degree of oil red O between group C4 and C3 is not statistically significant. (2) Compared with group A, the expressions of SREBP-1c mRNA in group B and C are raised by 1.218+/-0.130 and 1.798+/-0.118 times respectively, among group A, B, C, the expressions of SREBP-1c mRNA are statistically significant different ( F = 297.47, P is less than to 0.01). The expressions of SREBP-2 mRNA in group B and C are decreased by 0.956+/-0.118 and 0.972+/-0.153 times as compared to group A. However, the difference of SREBP-2 mRNA expression among the 3 groups is not statistically significant ( F = 0.568, P is more than to 0.05). Compared with group C1, SREBP-1c mRNA in group C2 is decreased by 0.714+/-0.081 folds (t=11.224, P is less than to 0.01), while SREBP-2 mRNA in group C2 is raised by1.034+/-0.155 times(t=0.692, P is more than to 0.05). SREBP-1c mRNA and SREBP-2 mRNA in group C4 are raised by 1.012+/-0.206 times and decreased by 0.998+/-0.183 times as compared to group C3 without difference found (t=0.196 or 0.031, P is more than to 0.05). (3) the expressions of SREBP-1c protein in group A, B and C are 36257.21+/-5709.79, 50413.47+/-4989.28 and 71025.83+/-6047.13 respectively, and the difference is statistically significant among the 3 groups (F = 178.26, P is less than to 0.01); the expressions of SREBP-2 protein in group A, B and C are 32913.52+/-3951.21, 32625.91+/-4025.06 and 34173.44+/-5316.25 respectively, but the difference is not statistically significant among the 3 groups ( F = 0.562, P is more than to 0.05), SREBP-1c protein levels in group C1, C2, C3, C4 are 69832.16+/-4941.36, 48735.47+/-5471.41, 70871.69+/-5083.14 and 68913.32+/-5343.22 respectively, the difference of SREBP-1c protein levels between group C1 and C2 is statistically significant (t=10.260, P is less than to 0.01); while the difference between group C3 and group C4 is not statistically significant(t=1.558, P is more than to 0.05). The expressions of SREBP-2 protein in group C1, C2, C3 and C4 are 33 980.21+/-4081.80, 34011.50+/-3859.27, 33610.12+/-4761.10 and 32915.66+/-5023.61 respectively, the difference of SREBP-2 protein levels in group C1 and group C2 is not statistically sign

Jiang, Cui-Ying; Zeng, Wei-Qiong; Chen, Ya-Xi; Dai, Fu-Hong; Jiang, Ping

2011-08-01

360

Keeping Track of Interactomes Using the ProHits LIMS  

PubMed Central

Affinity purification coupled with mass spectrometry (AP-MS) is a robust technique used to identify protein-protein interactions. With recent improvements in sample preparation, and dramatic advances in MS instrumentation speed and sensitivity, this technique is becoming more widely used throughout the scientific community. To meet the needs of research groups both large and small, we have developed software solutions for tracking, scoring and analyzing AP-MS data. Here, we provide details for the installation and utilization of ProHits, a Laboratory Information Management System designed specifically for AP-MS interaction proteomics that we distribute freely to the scientific community at ProHitsMS.com, and which is under continuous development. The complete ProHits solution1 performs scheduled backup of mass spectrometry data and initiates database searches (Mascot, X!Tandem, COMET, SEQUEST and the output from the TransProteomics Pipeline are now supported). It stores search results and enables linking the mass spectrometry data to entries in the relational database module called “Analyst”, which is also available as a stand-alone application (including as an easy-to-install virtual machine implementation2). ProHits Analyst is organized in a hierarchical manner by project, bait, experiment and sample and also serves as an electronic notebook. When a sample is created, mass spectrometry search results can be uploaded. Search results can be explored using a series of viewers, filtered based on mass spectrometry quality, frequency of detection or background lists, viewed in Cytoscape-Web or exported to text or as a PSI XML format for deposition in interaction databases. Importantly, however, search results can be further analyzed using the SAINT statistical tool which is seamlessly integrated within ProHits to derive interaction confidence scores(3-5). With the integration with a number of open source tools and public repositories, ProHits facilitates transparent analysis and reporting of AP-MS data. 1PMID:209445832PMID:229487303PMID:204890234PMID:211319685PMID:22948729

Liu, Guomin; Zhang, Jianping; Choi, Hyungwon; Raught, Brian; Nesvizhskii, Alexey I.; Tyers, Mike; Gingras, Anne-Claude

2013-01-01

361

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

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 ?2-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.

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

362

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

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 attached to PC2, the pro-region of pro-PC3 had no effect on the optimum pH for maturation (pH 5.5-6.0), but it did accelerate the rate of maturation (t12 2 h). These results demonstrate that Asp310 and the pro-region of pro-PC2 contribute to the acidic pH optimum and low rate of maturation of this zymogen relative to its closely related homologue PC3.

Scougall, K; Taylor, N A; Jermany, J L; Docherty, K; Shennan, K I

1998-01-01

363

ProB: an automated analysis toolset for the B method  

Microsoft Academic Search

We present ProB, a validation toolset for the B method. ProB's automated animation facilities allow users to gain condence in their specications. ProB also contains a model checker and a renement checker, both of which can be used to detect various errors in B specications. We describe the underlying methodology of ProB, and present the important as- pects of the

Michael Leuschel; Michael J. Butler

2008-01-01

364

InterPro-an integrated documentation resource for protein families, domains and functional sites  

Microsoft Academic Search

Motivation: InterPro is a new integrated documentation resource for protein families, domains and functional sites, developed initially as a means of rationalising the complementary efforts of the PROSITE, PRINTS, Pfam and ProDom database projects. Results: Merged annotations from PRINTS, PROSITE and Pfam form the InterPro core. Each combined Inter- Pro entry includes functional descriptions and literature references, and links are

Rolf Apweiler; Terri K. Attwood; Amos Bairoch; Alex Bateman; Ewan Birney; Margaret Biswas; Philipp Bucher; Lorenzo Cerutti; Florence Corpet; Michael D. R. Croning; Richard Durbin; Laurent Falquet; Wolfgang Fleischmann; Jérôme Gouzy; Henning Hermjakob; Nicolas Hulo; Inge Jonassen; Daniel Kahn; Alexander Kanapin; Youla Karavidopoulou; Rodrigo Lopez; Beate Marx; Nicola J. Mulder; Thomas M. Oinn; Marco Pagni; Florence Servant; Christian J. A. Sigrist; Evgeni M. Zdobnov

2000-01-01

365

On the mechanism of fasting-associated elevations in hypothalamic cyclo(His-Pro) content  

Microsoft Academic Search

Potential mechanism(s) underlying the fasting-associated rise in hypothalamic cyclo(His-Pro) content was explored by examining the effects of 24-hour fasting on: (i) cyclo(His-Pro) synthesis from TRH, (ii) cyclo(His-Pro) metabolism, and (iii) cyclo (His-Pro) secretion by hypothalamic tissue in vitro. The data presented here show that none of these three variables were altered due to fasting. Two additional potential changes that could

Chandan Prasad; Tokuji Iriuchijima; Ruth M. Edwards; John F. Wilber; Masatomo Mori; Deborah J. Rogers

1986-01-01

366

Cerebral Lateralization of Pro- and Anti-Social Tendencies  

PubMed Central

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.

2014-01-01

367

Bacterial inhibition of eukaryotic pro-inflammatory pathways  

Microsoft Academic Search

Eukaryotic cells perceive and respond to microbes, both pathogenic and commensal, by activation of signaling cascades such\\u000a as the NF-K B pathway. Induction of such pathways leads to the upregulation of a program of gene expression that mediates pro-inflammatory\\u000a and anti-apoptotic effector proteins. This host response is usually effective in clearing or controlling an infection. For\\u000a pathogens (and potentially, symbionts)

Andrew S. Neish

2004-01-01

368

Cervical arthroplasty using ProDisc-C case report.  

PubMed

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

Nica, D A; Copaciu, R

2013-03-15

369

HardCopy Pro 3.2.2  

NSDL National Science Digital Library

The HardCopy Pro program is a great way to capture screens of interest that might be of later use in a professional or recreational setting. Visitors can use the program to capture rectangular screen areas, and then manipulate the images via a cropping tool. Additionally, they can use the application to save the images in a variety of file formats. This version is free for 30 days, and it is compatible with computers running Windows XP and newer.

2010-06-22

370

ProFusion*: Intelligent Fusion from Multiple, Distributed Search Engines  

Microsoft Academic Search

The explosive growth of the World Wide Web, and the resulting information overload, has led to a mini-explosion in World Wide Web search engines. This mini-explosion, in turn, led to the development of ProFusion, a meta search engine. Educators, like other users, do not have the time to evaluate multiple search engines to knowledgeably select the best for their uses.

Susan Gauch; Guijun Wang; Mario Gomez

1996-01-01

371

Cerebral lateralization of pro- and anti-social tendencies.  

PubMed

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

Hecht, David

2014-03-01

372

Control of the Immune Response by Pro-Angiogenic Factors  

PubMed Central

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.

Voron, Thibault; Marcheteau, Elie; Pernot, Simon; Colussi, Orianne; Tartour, Eric; Taieb, Julien; Terme, Magali

2014-01-01

373

Inhibition of murine AIDS by pro-glutathione (GSH) molecules.  

PubMed

Antioxidant molecules can be used both to replenish the depletion of reduced glutathione (GSH) occurring during HIV infection, and to inhibit HIV replication. The purpose of this work was to assess the efficacy of two pro-GSH molecules able to cross the cell membrane more easily than GSH. We used an experimental animal model consisting of C57BL/6 mice infected with the LP-BM5 viral complex; the treatments were based on the intramuscular administration of I-152, a pro-drug of N-acetylcysteine and S-acetyl-beta-mercaptoethylamine, and S-acetylglutathione, an acetylated GSH derivative. The results show that I-152, at a concentration of 10.7 times lower than GSH, caused a reduction in lymph node and spleen weights of about 55% when compared to infected animals and an inhibition of about 66% in spleen and lymph node virus content. S-acetylglutathione, at half the concentration of GSH, caused a reduction in lymph node weight of about 17% and in spleen and lymph node virus content of about 70% and 30%, respectively. These results show that the administration of pro-GSH molecules may favorably substitute for the use of GSH as such. PMID:18164447

Fraternale, A; Paoletti, M F; Casabianca, A; Orlandi, C; Schiavano, G F; Chiarantini, L; Clayette, P; Oiry, J; Vogel, J-U; Cinatl, J; Magnani, M

2008-02-01

374

Tenocytes, pro-inflammatory cytokines and leukocytes: a relationship?  

PubMed Central

Summary Leukocyte derived pro-inflammatory mediators could be involved in tendon healing and scar formation. Hence, the effect of autologous leukocytes (PBMCs, peripheral blood mononuclear cells and neutrophils) on primary rabbit Achilles tenocytes gene expression was tested in insert assisted co-cultures. Subsequently, tenocytes gene expression of extra-cellular matrix (ECM) components (type I collagen, decorin, fibronectin), the cell-ECM receptor ?1-integrin, the angiogenic factor myodulin, ECM degrading matrix-metalloproteinase (MMP)1 and pro-inflammatory cytokines (interleukin [IL]-1?, tumour necrosis factor [TNF?] and IL-6) was analysed. The only significant effect of leukocytes on tenocytes ECM genes expression was a suppression of type I collagen by neutrophils combined with TNF? stimulation. The same effect could be observed analysing the ?1-integrin and myodulin gene expression. However, PBMCs up-regulated significantly cytokine and MMP1 gene expression in tenocytes. These in vitro results suggest that mononuclear cells could present an exogenic stimulus for the induction of pro-inflammatory and catabolic mediators in tendon.

Al-Sadi, Onays; Schulze-Tanzil, Gundula; Kohl, Benjamin; Lohan, Anke; Lemke, Marion; Ertel, Wolfgang; John, Thilo

2011-01-01

375

BH3 mimetics activate multiple pro-autophagic pathways.  

PubMed

The BH3 mimetic ABT737 induces autophagy by competitively disrupting the inhibitory interaction between the BH3 domain of Beclin 1 and the anti-apoptotic prot