bluuebunny/crossref_metadata_2025_split huggingface dataset:
The protooncogene c‐jun is transactivated by the X protein of hepatitis B virus and highly expressed in liver cancer
Authors: ROBINSON W. S. , TWU J‐S. , LAI M‐Y. , CHEN D‐S. 
Published: March 2008

AbstractA specific viral oncogenic mechanism has not been shown for hepatitis B virus (HBV), although persistent HBV infection has been strongly associated with the development of hepatocellular carcinoma (HCC). Most HCC in HBV carriers contain integrated viral sequences in host DNA and this raises the question of whether such integrations ever contribute to oncogenesis. HBV contains a gene (designated the hbx gene), which encodes a transcriptional transactivator protein capable of activating homologous and heterologous cis‐acting regulatory sequences. Among the regulatory sequences that are responsive to hbx are those of HBV and heterologous regulatory sequences in the long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV‐1) and Rous sarcoma virus, and regulatory sequences of simian virus 40 and the human β interferon gene. The diversity of regulatory sequence that appear to be activated by hbx suggests that the hbx protein acts by a general mechanism that is not DNA sequence specific and other cellular genes may be similarly transactivated. This property of hbx raises the question of whether hbx expression in infected hepatocytes may activate cellular genes that could play a role in HCC, and hbx has been shown to be expressed from integrated viral genomic DNA in some HCC. In this regard, hbx was found to activate transcription regulated by the promoter of the protooncogene c‐jun. c‐jun was found to be expressed at a very low level in normal liver tissue but at high levels in HCC of HBV‐infected patients.
Use of recombinant HCV antigen in the serodiagnosis of hepatitis C virus infection: Significant improvement in HCV antibody detection as compared with the first generation HCV C100‐3 ELISA and the synthetic peptide EIA tests
Authors: CHIEN D. Y. , CHOO Q‐L. , TABRIZI A. , KUO C. , McFARLAND J. , BERGER K. , LEE C. , SHUSTER J. R. , NGUYEN T. , MOYER D. L. , TONG M. , FURUTA S. , OMATA M. , FONG C. T. , TEGTMEIER G. , ALTER H. , SCHIFF E. , JEFFERS L. , HOUGHTON M. , KUO G. 
Published: March 2008

AbstractHepatitis C virus (HCV) infection can be detected by using immunoassay techniques that measure reactivity to viral protein antigens. In this study seven discreet proteins derived from HCV genomic coding sequences have been expressed, purified and characterized. Six proteins represent the structural regions of the core (C22‐3), the envelope (E1 and E2), and the non‐structural regions NS3 (C33C), NS3–NS4 (C100‐3) and NS5. The seventh, C25, is a chimeric fusion protein containing C33C, C100‐3 and C22‐3 regions. Using these recombinant proteins, multi‐antigen radioimmunoassays and enzyme immunoassays (EIA) were designed. The fusion protein, C25, was demonstrated to be an improved antigen for serodiagnosis of HCV antibody. Use of the C25 protein accelerated HCV antibody detection by 3–46 weeks in non‐A, non‐B hepatitis seroconversion cases and significantly increased the rate of detection in a paid donor population by 20%. The C25 assay also demonstrated excellent specificity in 2446 randomly selected low prevalence samples. The repeated reactive rate in this group of samples was 0.5%.Samples from volunteer blood donors pre‐selected for repeat reactivity with the first generation C100‐3‐based HCV antibody tests (n= 175) were tested using the C25 assay. The C25 assay detected 37.7% samples as reactive and 53.1% samples as non‐reactive. This result was in agreement with all other supplementary tests that include RIBATM, multi‐antigen assay, Abbott neutralization and peptide assay. The other 9.2% samples were classified as ‘indeterminant’ because these samples were only partially in agreement with some of the above supplementary tests.The C25 enzyme‐linked immunosorbent assay (ELISA), with its improved assay sensitivity, can identify additional HCV antibody reactive cases in both hepatocellular carcinoma and cryptogenic cirrhosis patients. The C25 and multi‐antigen EIA assays were used to investigate the vertical transmission of HCV. It was observed that these improved assays are able to detect antibodies in a vertical transmission case. The C25 ELISA was also compared with a synthetic peptide assay. The C25 assay was found to be superior to the peptide assay that performed poorly in the detection of the C33C only reactive samples.
Quantitative analysis of hepatitis C virus RNA by competitive nested polymerase chain reaction
Authors: CHAYAMA K. , TSUBOTA A. , ARASE Y. , SAITOH S. , IKEDA K. , SAKAI Y. , MATSUMOTO T. , KOBAYASHI M. , UNAKAMI M. , MORINAGA T. , KUMADA H. 
Published: March 2008

AbstractA method that allows the quantitation of hepatitis C virus (HCV) RNA is described. The RNA was extracted from serum samples and reverse transcribed. Target cDNA was then co‐amplified by nested polymerase chain reaction with a known amount of competitive template at various concentrations. Since this internal control DNA uses the same primers as those of the target and is distinguishable from the target cDNA after amplification by size, the initial concentration of the target could be estimated by comparing the intensity of the two bands of amplified DNA fragments. That is, if the starting amount of the cDNA and the competitive template are equal, the intensity of the two bands should also be equal. Using this method the amount of HCV RNA in serum samples obtained from 85 patients with chronic hepatitis type C was determined. There was as much as a 100 000‐fold difference in the levels of HCV RNA from patient to patient. A rapid decrease of HCV RNA in a patient treated with interferon is also described.
Translational regulation of hepatitis B viral gene expression
Authors: LO S. J. , SHEU S. Y. , LIN C‐G. 
Published: March 2008

AbstractAt least five species of unspliced mRNA of the hepatitis B virus (HBV), which are 3.5, 3.4, 2.4, 2.1 and 0.8 kb, have been identified. To study this amount of HBV proteins they were translationally regulated and both in vitro and in vivo experiments performed. The four in vitro synthesized RNA corresponding to the 2.1, 2.4, 3.4, and 3.5 kb mRNA, respectively, were translated in a rabbit reticulocyte lysate. In conjunction with in vivo transfection experiments, it was demonstrated that: (i) a preferential translational initiation is involved in the differential amount of surface antigens; (ii) the 2.1 kb mRNA is the template for the synthesis of the middle and major surface antigens in a ratio of about 1 : 4; (iii) the 2.4 kb mRNA, although containing sequences for coding the large, middle and major surface antigen, is primarily used for the synthesis of large surface antigens; (iv) both the core and pol proteins can be independently synthesized from the 3.4 kb mRNA (pregenome RNA) and the synthesis of pol protein is favourably carried out via a leaky scanning mechanism; (v) the 3.5 kb mRNA (pre‐C mRNA) is the template for the production of precore protein (the precursor of hepatitis B e antigen) but not for the synthesis of both core and pol proteins. Taken together, the results indicate that: (i) the translational initiation context of each HBV‐encoded protein plays a key role in determining the level of protein synthesis; (ii) the occurrence of bifunctional mRNA of pregenome RNA and 2.1 kb mRNA provides another alternative means for minimization of the viral genome size; (iii) the leaky scanning mechanism is involved in the expression of the second protein in bifunctional mRNA.
The functions of the p53 gene and gene product
Authors: QUARTIN R. S. , LEVINE A. J. 
Published: March 2008

Abstractp53 is a tumour suppressor protein involved in the regulation of the cell cycle. Mutation of the p53 gene and expression of mutant p53 protein are associated with many types of human neoplasia. Mutational hot spots at specific amino acid residues have been identified, and these hot spot mutations are differentially expressed in tumours of different tissue origins. Mutant p53 proteins exhibit properties that are functionally and biochemically altered from those of the wild‐type protein, including increased metabolic stability, loss of DNA and SV40 T antigen‐binding ability, and loss of growth suppressive functions. Further characterization of both wild‐type and mutant p53 proteins will provide insights into the mechanisms of tumour development.
Expression and stability of the hepatitis B pol protein in Escherichia coli
Authors: LIN C‐G. , YOU L‐R. , LO S. J. 
Published: March 2008

AbstractThe pGEX plasmid containing the gene of glutathione S‐transferase (GST) was employed to express various lengths of the hepatitis B virus pol protein in a form of fusion protein in Escherichia coli. Results of SDS‐PAGE and Western blot analyses indicated that: (i) expression of GST‐pol fusion proteins varied from undetectable to 30% of total protein in different clones; (ii) presence of the carboxyl terminus of the pol protein apparently lowered the expression amount of fusion proteins; (iii) some distinct pol protein bands of lower molecular weight were constantly detected in several clones. The presence of the smaller pol protein therefore raises a possibility that the pol protein contains protease cutting sites.
Different processing of bile canalicular antigen in well and poorly differentiated human hepatoma cell lines
Authors: CHIU J‐H. , HU C‐P. , LUI W‐Y. , CHANG H‐M. , CHANG C. 
Published: March 2008

AbstractHepatocytes, known as polarized epithelia, are composed of sinusoid, basolateral and bile canalicular domains. Using monoclonal antibody and human hepatoma cell lines, the canalicular domain was shown to be established in well‐differentiated lines via vesicle fusion, but not in poorly differentiated lines. To understand the metabolic processing of the bile canalicular antigen in different human hepatoma cell lines, monoclonal antibody C2D4 was produced by immunizing BALB/C mice with human hepatoms cell line HA22T/VGH and fusing sensitized mouse spleen cells with mouse myeloma cells. Using two‐dimensional polyacrylamide gel electrophoresis, the monoclonal antibody C2D4 was shown to react with the same molecule recognized by monoclonal antibody 9B2, which had been known to react with the antigen on the bile canalicular domain of human hepatocytes and hepatoma cells, both in vivo and in vitro. Analysed with pulse‐chase radioimmunoprecipitation, C2D4 precipitated the 140 kD polypeptide through a 1–4 day well‐differentiated cell line, Hep G2; whereas in addition to the 140 kD polypeptide, an 80 kD protein was recognized by C2D4 in a 2 or 3 day poorly differentiated line, SK‐HEP‐1. Together with peptide mapping and subcellular fractionation analysis, the 80 kD protein was postulated to be internally degraded in the intracellular compartment, but not on the cytoplasmic membrane. It was concluded that the human hepatoma cell lines could be a good in vitro model to study the metabolic processing of bile canalicular domains of human hepatocytes. Also, the loss of the cellular polarity in poorly differentiated human hepatoma cell lines provides a good natural variant to study the differentiation and progression of human hepatoma cells.
Variations in nucleotide sequence of the 5′ untranslated region of hepatitis C viruses
Authors: LEE C‐H. , CHENG C. , WANG J. , LUMENG L. 
Published: March 2008

AbstractThe nucleotide sequence of the 5′ untranslated region of hepatitis C viruses (HCV) has been shown to be conserved. In contrast, this study detected in the region of several HCV isolates more sequence variation than hitherto expected. The nucleotide sequences of the 5′ untranslated region of these isolates differ significantly from that of the prototype but are very similar to each other. This study considers these isolates as belonging to the same type of HCV. Among 240 HCV RNA polymerase chain reaction positive specimens that were examined, seven of them belong to this type. The results suggest that the HCV variants detected represent a different type of HCV and that they are responsible for approximately 3% of HCV infections in this part of the United States.
Hepatitis B virus antibody escape mutant from Singapore
Authors: HARRISON T. J. , VALLIAMMAI T. , HOPES E. A. , OON C. J. , ZUCKERMAN A. J. 
Published: March 2008

AbstractIn order to prevent perinatal infection, the child of a hepatitis B e antigen‐positive mother was given hepatitis B immune globulin and vaccinated against hepatitis B virus (HBV) at birth. Despite circulating antibody to hepatitis B surface antigen (anti‐HBs), the child became infected and is a carrier. Recent serum samples show the co‐existence of hepatitis B surface antigen and anti‐HBs. This study tries to determine whether failure to neutralize this virus by anti‐HBs was associated with a change in the amino acid sequence of the surface protein of HBV. The polymerase chain reaction was used to amplify the region of the hepatitis B surface open reading frame encoding the major antigenic determinants from serum samples taken from the child at 2, 5 and 6 years of age. Nucleotide sequence analysis of the products revealed a point mutation which resulted in a substitution of arginine for glycine at amino acid position (145) in the second loop of the a determinant.
Acute post‐transfusion hepatitis C in Taiwan: Evaluation of two generations of hepatitis C virus diagnostic enzyme immunoassay
Authors: LEE S‐D. , HWANG S‐J. , TSAI Y‐T. , LU R‐H. , LO K‐J. 
Published: March 2008

AbstractA total of 461 patients at the Veterans General Hospital, Taipei who had received blood transfusions since March 1981 were followed prospectively with serum biochemistry tests and viral hepatitis markers before and after the blood transfusions, periodically for at least 6 months. Sixty‐three (13.7%) patients developed post‐transfusion hepatitis (PTH). Of the patients with PTH, 71.4% were found to have antibody to hepatitis C virus (anti‐HCV) seroconversion during the 1 year follow‐up period by the first‐generation of the hepatitis C virus (HCV) enzyme immunoassay (EIA) antibody test, but the second‐generation EIA detected an increase to 88.9%. All sera positive by the first‐generation EIA were also positive by the second‐generation EIA. Their mean incubation of serum alanine aminotransferase (ALT) elevation was 6.5 weeks. The mean interval between the day of blood transfusion and the onset of active anti‐HCV seroconversion was 18.3 weeks if tested by the first‐generation EIA, but shortened to 9.5 weeks if tested by the second‐generation EIA. Of 49 acute PTH C patients who were followed up for more than 1 year, 32 (65.3%) still had abnormal serum ALT levels. The results of this study demonstrate that acute hepatitis C is a frequent and important complication in blood transfusions in Taiwan. The second‐generation HCV antibody EIA derived from HCV genes encoding both capsid and non‐structural proteins is more sensitive for detection of HCV infection than recombinant c100‐3 assay derived from the non‐structural region of the viral genome only.
A randomized controlled clinical trial of recombinant interferon α‐2b in the treatment of acute post‐transfusion hepatitis C: A preliminary report
Authors: HWANG S‐J. , LEE S‐D. , LEE Y‐H. W. , WU J‐C. , CHAN C‐Y. , HUANG Y‐S. , WANG Y‐J. , LO K‐J. 
Published: March 2008

AbstractTwenty patients with acute post‐transfusion hepatitis C were prospectively followed after blood transfusion. All had seroconversion of serum antibody to hepatitis C virus (anti‐HCV) or hepatitis C virus (HCV) RNA. They were randomly allocated to two groups. Ten patients received a subcutaneous injection of recombinant interferon (IFN) α‐2b, 3 million units (MU) thrice weekly for 3 months; this was generally 8 weeks after the first post‐transfusional elevation of serum alanine transaminase (ALT). Ten patients without specific treatment were selected as a control group. During the 3 month period, nine (90%, 95% CI = 54–99%) patients in the IFN‐treated group normalized serum ALT level, while only three (30%, 95% CI = 8–65%) in the control group normalized the serum ALT spontaneously (P < 0.01). Two (25%) of eight patients who initially showed a complete response to IFN‐treatment had serum ALT elevated again. After a 6 month follow‐up, five (63%, 95% CI = 26–90%) of eight patients in the IFN‐treated group and four (44%, 95% CI = 15–77%) of nine patients in the control group normalized serum ALT (P= 0.40). Among the nine patients who normalized serum ALT during IFN treatment, eight had undetectable serum HCV RNA and one showed a decreased level. Two patients had detectable serum HCV RNA accompanied by elevated serum ALT again after completion of the IFN treatment. After 6 months follow‐up four (50%, 95% CI = 17–83%) of eight patients lost their serum HCV RNA in the IFN‐treated group and two (22%, 95% CI = 4–60%) of nine patients spontaneously lost their HCV RNA in the control group (P= 0.25). All patients tolerated the IFN treatment well but had minor side effects such as fever, rigor, malaise, leukopenia, myalgia, headache and hair loss. In conclusion, recombinant IFN α‐2b injections in patients with acute post‐transfusion hepatitis C can successfully suppress the viral RNA and lead to normalization of serum ALT. Whether this regimen can prevent the development of chronicity needs further evaluation.
Hepatitis B vaccine trial in neonates
Authors: LO K‐J. , LEE S‐D. , TSAI Y‐T. , WU T‐C. , YU M‐Y. , WANG Y‐J. , CHAN C‐Y. 
Published: March 2008

AbstractIn an attempt to interrupt perinatal and postnatal transmission of hepatitis B virus (HBV) infection, hepatitis B vaccine trials were initiated in October 1981 in Taiwan, starting in neonates of hepatitis B e antigen (HBeAg)‐positive hepatitis B surface antigen (HBsAg) carrier mothers and extending to neonates of non‐carrier mothers. All neonates had received a four‐dose schedule of Pasteur plasma‐derived hepatitis B vaccine. Among neonates of HBeAg‐positive HBsAg carrier mothers, the protective efficacy rate of vaccination was 75% in those who received vaccine alone and 90% in those who received vaccine plus hepatitis B immunoglobulin (HBIG) at birth. Among neonates of HBeAg‐negative HBsAg carrier mothers, the protective efficacy rate was 100% whether they had received vaccine alone or vaccine plus HBIG at birth. The protective efficacy rate was also 100% in neonates of non‐carrier mothers. During 6–9 years of long‐term follow‐up, 12 (6%) responsive vaccinees of HBeAg‐positive carrier mothers, one (2%) child of HBeAg‐negative carrier mothers and one child (0.4%) of non‐carrier mothers had seroconverted to antibody to hepatitis B core antigen (anti‐HBc) positivity. ‘Natural booster’ phenomenon, defined as a spontaneous sharp rise in serum antibody to HBsAg (anti‐HBs) titres in the absence of anti‐HBc and HBsAg, was observed in 7% of vaccinees whose mothers were HBeAg‐positive, 6% of vaccinees whose mothers were HBeAg‐negative HBV carriers, and 8% in vaccinees of non‐HBV carrier mothers. None of the responsive vaccinees had seroconverted to HBsAg. Thus, in the first decade of life, the protective efficacy in neonates who responded to plasma‐derived hepatitis B vaccine was 100%.
A two year controlled trial examining the effectiveness of ursodeoxycholic acid in primary biliary cirrhosis
Authors: TURNER IAN B. , MYSZOR MARGARET , MITCHISON HARRIET C. , BENNETT MARK K. , BURT ALISTAIR D. , JAMES OLIVER F. W. 
Published: March 2008

Abstract Forty‐six patients with primary biliary cirrhosis from a single centre were studied in a randomized placebo‐controlled trial to determine the effectiveness of ursodeoxycholic acid (UDCA) over a 2 year period. The two groups were well‐matched at baseline. For each parameter, by calculating the difference between the median changes with time between the UDCA group and the placebo group, it was found that from entry, with respect to placebo, there were differences between median changes (MCD) favouring the UDCA group in bilirubin {MCD 5 μmol/L [95% confidence interval (CI) 1 to 12] at 1 year and 5 μmol/L (95% CI 1 to 9) at 2 years}, alkaline phosphatase MCD 242 iu/L (95% CI 107 to 360) at 1 year and 268 iu/L (95% CI 146 to 424) at 2 years and aspartate aminotransferase MCD 26 iu/L (95% CI 12 to 41) at 1 year and 37 iu/L (95% CI 16 to 64) at 2 years. Within the UDCA group, there was long‐term fall in alkaline phosphatase [median fall 116 iu/L (95% CI 93 to 378) at 2 years and aspartate aminotransferase [median fall 18 iu/L (95% CI 6 to 47) at 2 years; however, the major change in bilirubin was a modest rise over 2 years in the placebo group [median rise 2 μmol/L (95% CI 1 to 9)]. Changes in albumin, prothrombin ratio and immunoglobulins were generally minor and not significant.Ursodeoxycholic acid did not generally influence stage progression or histological features, although a smaller percentage of non‐cirrhotic patients were documented as having developed cirrhosis on UDCA compared to placebo (14 vs 57%) over the 2 years. There appeared to be no consistent effect on pruritus and general well‐being. The medication was well‐tolerated and safe. In conclusion, UDCA appears to have beneficial effects on some serum biochemical markers in primary biliary cirrhosis and so may have a role in retarding disease progression. It could be useful in combination with an immunosuppressive or an anti‐fibrotic agent.
Clinical characteristics and proliferating activity of intrahepatic cholangiocarcinoma
Authors: OHASHI KAZUO , NAKAJIMA YOSHIYUKI , TSUTSUMI MASAHIRO , KANEHIRO HIROMICHI , FUKUOKA TOSHIYUKI , HISANAGA MICHIYOSHI , TAKI JUNICHIRO , NAKAE DAI , KONISHI YOICHI , NAKANO HIROSHIGE 
Published: March 2008

Abstract To assist in the development of new approach to the palliation and treatment of intrahepatic cholangiocarcinomas, we classified tumours into mass‐forming (MF), peri‐ductal extension (PD), and spicula‐forming (SF) types in 14 subjects who underwent surgical treatment. Lymph node metastasis and microscopic lymphatic invasion were pronounced in the PD and SF types. Furthermore, in SF type tumours the incidence of microscopic vascular and perineural invasion was high. The proliferating cell nuclear antigen labelling index, a reflection of the proliferation rate of tumour cells, was significantly higher in PD and SF types than in the MF type. The prognosis associated with the MF type tended to be better than that of the other two types.For the MF type, liver resection with tumour free margins must be performed, whereas for the PD and SF types, aggressive treatment, that is a combination of extensive liver resection, lymph node dissection, and effective adjuvant anti‐cancer therapy should be provided to aim at life‐long cure.