Browsing by Author "Lee, Samuel S."
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Item Open Access Cardiac Beta-adrenergic receptor function & plasma membrane physical properties in cirrhotic cardiomyopathy(1995) Ma, Zenghua; Lee, Samuel S.Item Open Access Cardiac Beta-adrenergic receptor function and plasma membrane physical properties in cirrhotic cardiomyopathy(1995) Ma, Zenghua; Lee, Samuel S.Item Open Access Compartmental Hepatitis B Virus (HBV) Evolution, Replication and Infectivity in vivo and ex vivo(2017) Gao, Shan; Coffin, Carla S; Lee, Samuel S.; Duan, Zhongping; Van Marle, Guido; van der Meer, FrankHepatitis B Virus (HBV) is classically considered a hepatotropic virus, however, the presence of different HBV genomic molecules in lymphoid cells and tissues support its lymphotropic nature. Our previous studies showed that HBV evolved in a compartment- and disease phase-specific fashion. However, the effect of nucleos/tide analogue (NA) therapy on HBV evolution and replication in different compartments (i.e., liver, plasma and peripheral blood mononuclear cell (PBMC)) is unknown, as well as the replicative competence and infectious capacity of PBMC-derived HBV. We hypothesize that HBV replicating in lymphoid cells is infectious, and the HBV evolves in PBMC and/or plasma in chronic hepatitis B (CHB) patients under the influence of NA therapy or host immune pressure (i.e., fulminant hepatitis B). The study on HBV replication and genetic evolution in PBMC, liver and plasma of CHB patients under NA therapy revealed the HBV evolution varied between three compartments both before and after treatment. NA had little effect on HBV cccDNA level and persistence of mRNA in PBMC. The study on HBV genetic features in CHB carriers with acute-on-chronic liver failure (ACLF) revealed the frequent immune escape mutations with clusters of surface gene variants possibly associated with development of fulminant hepatitis B. Mitogen stimulation in PBMC of CHB patients revealed presence of replicating HBV, which can be upregulated in PBMC and exhibited infectious capacity to HepaRG cells in vitro. In summary, our data suggests potent NAs have little effect on HBV cccDNA in liver and PBMC, which highlights the need for continued suppressive antiviral therapy. The HBV evolution varied between different compartments in CHB patients under NA therapy. Distinct variants in HBV surface gene were found to be associated with HBV fulminant hepatitis. Moreover, HBV residing in lymphoid cells is increased after mitogen stimulation of PBMC and infectious to a hepatocyte cell line. The study furthers our understanding of HBV lymphotropism, role on viral persistence and the pathogenesis of chronic hepatitis B.Item Open Access Hepatitis B Virus (HBV) Variants in Untreated and Tenofovir Treated Chronic Hepatitis B (CHB) Patients during Pregnancy and Post-Partum Follow-Up(PLoS One, 2015-10-16) Virine, Boris; Osiowy, Carla; Gao, Shan; Wang, Tong; Castillo, Eliana; Martin, Steven R.; Lee, Samuel S.; Simmonds, Kimberley; van Marle, Guido; Coffin, CarlaBACKGROUND: Chronic hepatitis B (CHB) is a dynamic disease that may be affected by immune changes in pregnancy. Guidelines suggest consideration of nucleos/tide analogs (NA), i.e., tenofovir, (TDF) in highly viremic mothers to reduce vertical transmission risk. HBV variability affects CHB outcome, but little is known about HBV genetic changes in pregnancy due to immune or NA selection. OBJECTIVES: To evaluate HBV diversity in NA treated or untreated pregnant vs. post-partum CHB carriers. STUDY DESIGN: In plasma collected from 21 mothers (7 matching pre/post-partum), HBV serological tests, genotype and viral load were assayed. The HBV pre-surface (S) /S overlapping polymerase (P) (N = 20), pre-core (C) /C (N = 11) and/or full genome PCR amplicons (N = 3) underwent clonal sequence analysis. RESULTS: The median age was 31 y, 71% Asian, 68% genotype B or C, 33% HBV eAg+, 5 received TDF (median HBV DNA 8.5 log IU/ml). In untreated mothers, median antepartum vs. post-partum ALT was 21 vs. 24 U/L and HBV DNA was 2.7 vs. 2.4 log(10) IU/ml. ALT and/or HBV DNA flares occurred during pregnant and/or post-partum period in 47% (10/21). Clonal sequencing antepartum showed the presence of minor "a determinant" and/or vaccine escape mutants (VEM) but drug resistant variants were infrequent. Analysis of pregnant vs. post-partum samples showed different HBV variants and viral diversity. CONCLUSIONS: Differences in immune and/or by NA selective pressures during pregnancy may affect HBV evolution during pregnancy. The presence of minor VEM warrant infant follow-up.Item Open Access Immediate early gene expression in the central nervous system in portal hypertension: functional and immunohistochemical studies(2002) Song, Daisheng; Lee, Samuel S.Item Open Access Muscarinic receptor function and characteristics in cirrhotic cardiomyopathy(1996) Jaue, Debbie N.; Lee, Samuel S.Item Open Access Role of adhesion molecules in chronic liver allograft rejection(1997) Wong, John; Lee, Samuel S.Item Open Access Role of endocannabinoid system in development of cardiac dysfunction in cirrhosis(2009) Gaskari, Seyed Ali; Lee, Samuel S.Item Open Access Role of titin and collagen in the diastolic dysfunction of cirrhotic cardiomyopathy(2008) Glenn, Tamara; Lee, Samuel S.Item Open Access Vasoactive effects of bile salts in cirrhosis(1994) Pak, Jung-Min; Lee, Samuel S.