摘要:

AbstractIn this paper, the recent development in the study of the epidemiology of hepatocellular carcinoma (HCC) and the diagnosis of adenomatous hyperplastic nodules as a putative preneoplastic lesion are discussed. Other clinical features of HCC will not be included here.

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1993.tb01666.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 develo

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1993.tb01682.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1993.tb01671.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 thehbxgene), which encodes a transcriptional transactivator protein capable of activating homologous and heterologouscis‐acting regulatory sequences. Among the regulatory sequences that are responsive tohbxare 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 byhbxsuggests that thehbxprotein acts by a general mechanism that is not DNA sequence specific and other cellular genes may be similarly transactivated. This property ofhbxraises the question of whetherhbxexpression in infected hepatocytes may activate cellular genes that could play a role in HCC, andhbxhas been shown to be expressed from integrated viral genomic DNA in some HCC. In this regard,hbxwas found to activate transcription regulated by the promoter of the protooncogene c‐jun.c‐junwas found to be expressed at a very low level in normal liver tissue but at high levels in HCC of HBV‐infecte

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1993.tb01674.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractHepatocellular carcinomas have been known to exhibit a poor response to chemotherapeutic agents. However, the mechanism for drug resistance is unknown. Recent studies have demonstrated that expression of a group of membrane proteins known as P‐glycoproteins (P‐gp) or multidrug transporters encoded by multidrug‐resistance (MDR) or P‐glycoprotein gene family is correlated with a poor clinical prognosis for particular non‐responsive neoplasms. The possible involvement ofMDRgene expression with the intrinsic poor response to chemotherapeutic agents is

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1993.tb01675.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractHepatitis B virus infection is preventable by vaccine and the correlate of immunity is the induction of antibody. The 2.5 μg antigen per dose of H‐B‐VAX II given in appropriate regimens is adequate to immunize normal newborn infants and children up to 11 years of age. A 5 μg dose may be needed to protect newborn infants born to mothers who are carriers of hepatitis B infection and should be used when the carrier status is either positive or is unknown. The immune response in newborn infants is usually of lower titre than in infants who are 2–3 months of age or older. The level of protection afforded in otherwise healthy individuals by plasma‐derived vaccine is high and lasts for longer than 7 years, even though the level of circulating antibody may have declined to a less than detectable amount. A similar pattern of antibody decline follows administration of recombinant vaccine. The mechanism for sustained protection is in long‐term immunological memory with rapid recall of antibody production on exposure to the virus in nature. Administration of hepatitis B vaccine will be simplified by combination with DPT and poliomyelitis vaccines in single‐dose formulations that are under current development.An experimentally killed hepatitis A virus vaccine prepared by formaldehyde inactivation of attenuated live virus purified from infected MRC‐5 cell cultures induces rapid and high level antibody response when the vaccine is given in as little as 100 ng of antigen per dose and in two‐ or three‐dose regimens. The vaccine is highly protective when assayed in challenge studies in animals and the levels of antibodies achieved are far in excess of those provided by immune globulin when used for passive protection in humans. Field investigations to demonstrate protective efficacy against natural challenge in human beings have been in progress and protective efficacy h

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1993.tb01676.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

AbstractThe Government‐sponsored hepatitis B vaccination programme in Hong Kong was initiated in 1982. The programme initially provided hepatitis B vaccine and hepatitis B immunoglobulin (HBIG) to newborns of carrier mothers only. During the past 8 years, the programme has expanded to include medical and health personnel, medical and dental students and dialysis patients. Universal vaccination of all newborns was implemented in 1988, with a 98% acceptance rate. In the near future the programme will extend to cover children born before 1988 and other polytransfused subjects. In addition, the medical community has been active in public education and in the encouragement of vaccination of other high risk groups. It is hoped that by the beginning of the twenty‐first century, most of the susceptible subjects in Hong Kong will have been vaccina

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1993.tb01677.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1993.tb01678.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 detect

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1993.tb01679.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 descri

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1993.tb01680.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY