A5064451261- Hepatitis B Virus Studies
- Hepatitis C virus research
- HIV/AIDS drug development and treatment
- Liver Disease Diagnosis and Treatment
- Asthma and respiratory diseases
- Biochemical and Molecular Research
- Respiratory and Cough-Related Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- HIV Research and Treatment
- Animal Virus Infections Studies
- Prostate Cancer Diagnosis and Treatment
- Prostate Cancer Treatment and Research
- Genetic Associations and Epidemiology
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Pediatric health and respiratory diseases
- Viral gastroenteritis research and epidemiology
- Insect Resistance and Genetics
- Pneumocystis jirovecii pneumonia detection and treatment
- Hormonal and reproductive studies
- Sexual function and dysfunction studies
- Cytomegalovirus and herpesvirus research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Hepatitis Viruses Studies and Epidemiology
- Quinazolinone synthesis and applications
PAREXEL International (United States)
2019-2022
Research Triangle Park Foundation
2002-2019
GlaxoSmithKline (United States)
2003-2019
Triangle
2019
GlaxoSmithKline (Netherlands)
2011
Cardiff University
2005-2006
KU Leuven
2005-2006
GlaxoSmithKline (Belgium)
2005-2006
Rega Institute for Medical Research
2005-2006
Wellcome Library
1998
Cirrhosis and hepatocellular carcinoma occur as long-term complications of chronic hepatitis B virus (HBV) infection. Antiviral therapy is potentially a successful approach for the treatment patients with HBV infection, which includes nucleoside analog, lamivudine [(-)2′-deoxy-3′-thiacytidine, 3TC]. Although resistance to has been reported in several HBV-infected patients, pattern resistance-associated mutations not fully characterized. We report DNA sequence database that 500-base pair...
YMDD variants of hepatitis B virus (HBV) emerge in some patients with chronic who receive lamivudine. were examined 794 4 controlled studies 1 year's duration. The long-term effects a subset treated up to years. detected by polymerase chain reaction (PCR) and restriction fragment-length polymorphism assays. After year, 81 (24%) 335 patients. In these patients, the median serum HBV DNA concentration at year was <20% baseline level, alanine transaminase (ALT) levels liver histologic findings...
A study in Chinese patients with chronic hepatitis B showed that treatment lamivudine for 1 year significantly improves liver histology and enhances e antigen (HBeAg) seroconversion compared placebo. Fifty–eight from this 1–year have received long–term 100 mg; the outcome of 3 years is reported here. Before treatment, all had detectable HBeAg. HBeAg (HBeAg–negative, anti–HBe-positive), virus (HBV)–DNA suppression, alanine transaminase (ALT) normalization, emergence YMDD variant HBV,...
This placebo controlled, double–blind study evaluated the efficacy and safety of lamivudine in patients with hepatitis B e antigen (HBeAg)–negative/hepatitis virus (HBV) DNA-positive chronic B. Patients were randomized to receive 100 mg orally once daily for 52 weeks (n = 60) or 26 65). who HBV DNA positive at week 24 withdrawn 26. The primary endpoint was loss serum plus normalization alanine transaminase (ALT) 24. A significantly higher proportion receiving (63%) had a complete response...
BackgroundOrthotopic liver transplantation for end-stage hepatitis-B-virus (HBV) infection is commonly complicated by recurrence of HBV. Lamivudine, a cytosine nucleoside analogue, has been shown to suppress HBV infection. We report the development resistance lamivudine in three patients who underwent disease secondary hepatitis B.MethodsTwo received recurrent after transplantation, whereas third patient began treatment 1 month before an attempt prevent transplantation. The initially...
Seventy–seven liver transplant candidates were enrolled in a multicenter study which patients treated with lamivudine (100 mg daily) without the adjunctive use of hepatitis B immune globulin. Treatment was begun while awaited transplantation and continued after transplantation. All surface antigen (HBsAg) positive, 61% had detectable e (HBeAg) HBV DNA when treatment begun. Forty–seven underwent 30 did not. Median participation 38 months (range, 2.7–48.5) transplanted 26 0.1–37)...
The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits treatment with interferon are outweighed by serious side effects risk fatal exacerbation disease activity. Lamivudine rapidly reduces virus (HBV)-DNA in serum to undetectable levels. We have treated 35 patients lamivudine 100 mg or 150 orally once daily. Pretreatment, all were positive for HBV-DNA serum. Ten had Child-Pugh class 25 C liver disease. Seven underwent transplantation within 6...
Lamivudine therapy induces improvements in chronic hepatitis B a high proportion of patients, but prolonged is limited by the development viral resistance. We analyzed clinical responses and virologic resistance 27 patients treated continuously with lamivudine for 2 to 4 years. Serum transaminases, virus (HBV) DNA both branched (bDNA) signal amplification quantitative polymerase chain reaction were monitored at 4- 8-week intervals. Virologic was confirmed presence mutations YMDD motif gene...
The template for synthesis of hepadnaviral RNAs is a covalently closed circular (ccc) DNA located in the nucleus infected hepatocyte. Hepatocytes are normally long-lived and nondividing, antiviral therapies chronically individuals face problem eliminating not only replicative forms viral found cytoplasm but also cccDNA from nucleus. Because does replicate semiconservatively, it an obvious target therapy. However, elimination might be facilitated if its half-life were short comparison to...
Few studies have examined Chinese patients with chronic hepatitis B who exhibit surface antigen (HBsAg) seroclearance. We comprehensively studied the biochemical, virological, histological, and clinical aspects of 92 HBsAg seroclearance (median follow-up, 126 months). Ninety-two HBsAg-positive controls matched for age, sex, duration follow-up were also recruited. Liver biochemistry, serum virus (HBV) DNA levels, development complications monitored. Intrahepatic total covalently closed...
In patients with chronic hepatitis B, brief lamivudine therapy suppresses B virus (HBV) DNA but results infrequently in sustained losses of replication posttreatment. We evaluated treatment response and its posttreatment durability during up to 18 months (100 mg/d) 24 who had e antigen (HBeAg) despite 1 3 prior therapy. Therapy was be stopped after HBeAg loss or seroconversion (acquisition antibody HBeAg); monitoring continued for 6 months. During therapy, which well tolerated, HBV became...
Lamivudine is a nucleoside analog with activity against human immunodeficiency virus (HIV) and hepatitis B (HBV). Patients coinfected HIV HBV may have flares when lamivudine therapy discontinued or resistance of to emerges. This retrospective, descriptive study conducted in three tertiary care medical centers describes patients type 1 who presented spectrum clinical subclinical hepatitic responses withdrawal resistance. One patient had fulminant hepatic failure second was more efficacious...
Hepatitis B viruses establish a chronic, productive, and noncytopathic infection of hepatocytes. Viral products are produced by transcription from multiple copies (5–50) covalently closed circular (ccc) viral DNA. This cccDNA does not replicate, but can be replaced DNA precursors that synthesized in the cytoplasm. The present study was carried out to determine if long-term treatment with an inhibitor synthesis would lead loss virus products, including cccDNA, liver woodchucks chronically...
Duck hepatitis B virus (DHBV) is produced in small amounts following transfection of human hepatoma or hepatoblastoma cell lines with cloned viral DNA. In a search for better hosts DHBV replication, two avian liver were investigated. One these lines, LMH, 5 to 10 times more DNA replicative intermediates and 20 infectious than did either the HuH-7 Hep G2. Utilization genetic analyses replication often dependent upon obtaining efficient complementation between cotransfected genomes. We assayed...
Circulating androgen levels are often used as indicators of physiological or pathological conditions. More than half the variance for circulating is thought to be genetically influenced. A genome-wide association study (GWAS) has identified two loci, SHBG at 17p13 and FAM9B Xp22, serum testosterone (T) levels; however, these explain only a small fraction inter-individual variability. To identify additional genetic determinants levels, GWAS baseline T dihydrotestosterone (DHT) was conducted...
Famciclovir (FCV) and lamivudine (LAM) reduce viral replication in patients with recurrent hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). Eighteen of 20 insufficient response to FCV were treated 100 mg LAM daily OLT. These had shown nonresponse (n = 5), partial 7), or breakthrough 6) during therapy. Despite passive immunoprophylaxis immunoglobulin transplantation, HBV reinfection occurred 14 15 transplanted patients. HBV-DNA levels the regions A E polymerase...
Hepatitis B viremia and emergence of hepatitis virus (HBV) YMDD variants with reduced susceptibility to lamivudine were analyzed in patient sera from a phase II study extended therapy. Within 12 weeks, all patients exhibited marked virologic response lamivudine: >99% reduction (median 5 log decrease) serum HBV DNA levels. Virus remained at >104 genomes/mL 11 decreased <104 the remaining patients. In 10 patients, detectable emerged during course treatment. Six including 3 variants,...
ABSTRACT Two novel assays, a restriction fragment length polymorphism (RFLP) assay and an based on the 5′-nuclease activity of Taq DNA polymerase, were developed for screening viral variants in lamivudine-treated patients’ sera containing <1,000 copies hepatitis B virus (HBV) genome per ml. Both assays designed to detect single-nucleotide changes within HBV polymerase gene that are associated with lamivudine resistance vitro have been used screen number variant virus. Results obtained...
We report the first application of pronucleotide (ProTide) technology to antiviral agent abacavir (Ziagen), used for treatment HIV infection. The phenylmethoxyalaninyl phosphoramidate was prepared in good yield one step. Also corresponding guanine nucleoside analogue "carbovir". profile each parent nucleosides compared that ProTides. A significant (28- 60-fold) increase anti-HIV potency noted ProTide but not carbovir. These findings were agreement with markedly higher (ca. 37-fold) levels...
We aimed to evaluate the pharmacodynamics, efficacy, safety and tolerability of JAK1 inhibitor GSK2586184 in adults with systemic lupus erythematosus (SLE). In this adaptive, randomized, double-blind, placebo-controlled study, patients received oral 50-400 mg, or placebo twice daily for 12 weeks. Primary endpoints included interferon-mediated messenger RNA transcription over time, changes Safety Estrogen Lupus National Assessment-SLE Disease Activity Index score, number/severity adverse...
A novel rare mutation, homeobox B13 ( HOXB13 ) G84E, was reported to co-segregate with prostate cancer (PCa) in hereditary PCa families and associate risk unrelated cases controls. In this study, we aim compare the G84E mutation frequency among subjects of different races/ethnicities from various geographic regions world assess its for developing PCa, Reduction by Dutasteride Prostate Cancer Events (REDUCE) trial. All 3508 had initial negative biopsy were biopsied at Year 2 4 detection PCa....
ABSTRACT Lamivudine [(−)-β- l -2′,3′-dideoxy-3′-thiacytidine] reduces woodchuck hepatitis virus (WHV) titers in the sera of chronically infected woodchucks by inhibiting viral DNA synthesis. However, after 6 to 12 months, WHV begin increase toward pretreatment levels. Three variants with mutations active site polymerase gene are present at this time (W. S. Mason et al., Virology 245:18–32, 1998). We have asked if these mutant viruses were responsible for lamivudine resistance and their...