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Biomedical subjects

D S Chen

Publications and source records attributed to D S Chen.

At least 55 records · Page 3Linked to original sources

Hepatitis A vaccine in healthy adults: a comparison of immunogenicity and reactogenicity between two- and three-dose regimens.

Inactivated hepatitis A virus (HAV) vaccine was administered to 55 healthy seronegative adult volunteers to evaluate the immunogenicity and adverse reactions of two doses of HAV vaccination (25 units) in comparison with a three-dose regimen. The volunteers were randomly assigned to receive one of the two regimens: 26 were vaccinated with two doses at 0 and 24 weeks (Group 1), and 29 were vaccinated with three doses at 0, 2, and 24 weeks (Group 2). The vaccine was well tolerated and there was no serious adverse reaction. In both groups, the seroconversion rate was 100% at week 28. At week 52, all remained positive for anti-HAV regardless of a two- or three-dose regimen. No statistically significant difference in seroconversion rates and geometric mean titers could be demonstrated between the two groups. Thus, the two-dose regimen may be favorable to save cost and time for active immunization against hepatitis A.

Adult↗

Loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in Taiwan.

Elucidation of the basic genetic changes of human hepatocellular carcinoma is important for the understanding and treatment of this cancer. We used microsatellite polymorphism markers to study 30 cases of hepatocellular carcinoma (34 tumours) on all human chromosomes. DNA from 34 pairs of hepatocellular carcinomas and corresponding non-tumour parts was prepared. Loss of heterozygosity (LOH) and microsatellite instability on 23 chromosomes were investigated by 231 sets of microsatellite markers. More than 20% LOH was shown for loci on 16q (47.1%), 13q (32.4%), 17p (32.4%), 5q (26.5%), 11p (23.5%) and 9p (20.6%). The commonly affected regions were mapped to 16q12.1, 16q12.2, 16q24, 13q12.1-32, 17p13, 5q32, 5q34, 5q3, 11p15, 11q23-24 and 9p21. Hepatitis B virus carriers had a significantly higher frequency of LOH on chromosomes 5q, 11p and 16q. Furthermore, larger tumour size tended to have higher frequency of LOH at D16S409 locus (16q12.1). Microsatellte instability was only found in 12 of 231 markers and the frequency is very low. These data suggest that the chromosomes 16q, 13q, 17p, 5q, 11p and 9p might participate in hepatocarcinogenesis. However, microsatellite instability might play little role in the development of this cancer in Taiwan.

Adult↗

Minimal role of GB virus-C/hepatitis G virus in fulminant and subfulminant hepatitis in Taiwan.

BACKGROUND: The role of GB virus-C/hepatitis G virus (GBV-C/HGV) in fulminant hepatitis (FH) and subfulminant hepatitis (SFH) remains unclear. METHODS: Thirty-two FH or SFH patients, with adequate clinical information and serum specimens, were studied. Serum samples were tested for hepatitis markers and genomes of hepatitis A-E viruses, as well as GBV-C/HGV. RESULTS: Of the cases of FH/SFH studied, one (3%) was caused by anti-tuberculosis agents, 26 (81%) had hepatotropic virus infection, and five (16%) had no identifiable cause. Of the 26 patients with hepatotropic virus infection, five had acute hepatitis B infection (one with acute hepatitis D virus (HDV) co-infection), one had acute hepatitis C infection, 16 were hepatitis B surface antigen carriers with reactivation or superimposed by unidentified agent(s) (two had triple virus infections), three were hepatitis B carriers with HDV superinfection, and one had GBV-C/HGV infection in addition to exposure to halothane. GBV-C/HGV-RNA was detected in only three of 32 patients (9%) and all had a history of blood transfusion or co-existing causative factors. Of the 26 patients with hepatotropic virus infection, 18 were tested for antibodies against GBV-C/HGV envelope protein and seven were reactive, suggesting past infection. CONCLUSIONS: The role of GBV-C/HGV in causing FH and SFH is minimal in Taiwan and HBV infection remains the major aetiology. These findings also suggest the existence of as yet unrecognized agents, responsible for such catastrophic illnesses.

Adult↗

Comparison of two methods for quantification of hepatitis B viral DNA.

BACKGROUND: Quantitation of serum hepatitis B virus (HBV) DNA has proven useful in assisting with patient management and treatment and several commercially available assays have been developed to quantify serum HBV-DNA levels. METHODS: The performance of the cross-linking assay and the branched-DNA signal amplification (bDNA) assay for the quantitative measurement of HBV-DNA was studied in 99 hepatitis B surface antigen-positive and viraemic patients. RESULTS: Of these samples, 82 (83%) were positive for HBV-DNA by both assays and four (4%) were below the cut-off for both assays. Of the remaining 13 samples, 10 contained measurable levels of HBV-DNA by the cross-linking assay alone and three other samples contained measurable levels of HBV-DNA by the bDNA assay alone. The sensitivity gain of the cross-linking assay relative to bDNA assay in this study population was 10/92 (11%). In addition, a linear regression analysis showed that the HBV-DNA levels obtained from both assays was significantly correlated (gamma=0.974, P< 0.0001). CONCLUSIONS: These findings suggest that the recently developed cross-linking assay is more sensitive than the bDNA assay for the quantitative determination of HBV-DNA.

DNA, Viral↗

Prospects for hepatitis B virus eradication and control of hepatocellular carcinoma.

Hepatitis B virus infection is the most common cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. In areas hyperendemic for HBV infection, the related complications occur mostly during adulthood. However, nearly half of all primary infection in chronic carriers occurs in the perinatal period through maternal transmission, the other half arising from horizontal transmission mainly through intrafamilial spread or injection using unsterilized needles. A universal vaccination programme is better than immunization for at-risk groups. Hepatitis B vaccination should be integrated into the Expanded Programme on Immunization in children. Universal immunization against hepatitis B virus has proved to be effective in reducing the hepatitis B carrier rate to one-tenth of the prevalence before the vaccination programme in highly endemic areas, and the incidence of hepatocellular carcinoma in children has also been shown to be significantly reduced. Continued efforts to implement universal vaccination programmes worldwide will very likely reduce the incidence of hepatitis B virus-related diseases, particularly liver cirrhosis and hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Interferon-ribavirin for chronic hepatitis C with and without cirrhosis: analysis of individual patient data of six controlled trials. Eurohep Study Group for Viral Hepatitis.

BACKGROUND & AIMS: The aim of this study was to compare interferon (IFN)-ribavirin combination therapy with IFN monotherapy in chronic hepatitis C with particular focus on its efficacy in cirrhosis. METHODS: A multivariate analysis of individual patient data of all randomized controlled trials using an IFN-ribavirin arm, reported between 1991 and March 1998, was performed. Centers included 1 Asian and 5 European university-based referral centers for liver disease. A total of 197 patients with chronic hepatitis C received IFN-alpha (3 MU three times weekly) and ribavirin (1-1.2 g daily) for 6 months, and 147 patients received IFN-alpha (3 MU three times weekly) for 6 months. Patients were characterized according to previous IFN therapy, presence of cirrhosis, and genotype 1. Efficacy of therapy was evaluated by assessing the sustained response rate by logistic regression analysis. RESULTS: Patients without cirrhosis treated with IFN-ribavirin had a significantly higher sustained response rate than those treated with IFN, approximately 3-fold for previously untreated patients (IFN-ribavirin: genotype 1, 33%; genotype 2/3, 65%; IFN: genotype 1, 8%; genotype 2/3, 24%). In cirrhosis, sustained response rates with IFN-ribavirin (previously untreated: genotype 1, 7%; genotype 2/3, 24%) were also significantly higher than those with IFN (previously untreated: genotype 1, 1%; genotype 2/3, 5%). Clinical relevant superiority of combination therapy over IFN monotherapy was also observed for relapse; the same trend was observed for nonresponders. Tolerance for IFN-ribavirin was similar for patients with or without cirrhosis. CONCLUSIONS: Combination with ribavirin significantly enhances the sustained response rate of IFN therapy in major patient types (cirrhosis, genotype 1) with chronic hepatitis C. Thus, IFN-ribavirin combination is likely to become the antiviral therapy of choice for cirrhosis caused by hepatitis C.

Adult↗

Hepatitis B virus infection and hepatocellular carcinoma: molecular genetics and clinical perspectives.

Chronic hepatitis B progresses across a spectrum of asymptomatic carriers, active hepatitis, and liver cirrhosis. With more advanced disease stage, the risk for developing hepatocellular carcinoma (HCC) becomes higher. Recent studies suggest that this progressive risk may reflect an accumulation of multistage genetic mutations in the chromosomes of affected hepatocytes. Mutations of the known candidate genes such as p53 and beta-catenin have been found. Recent genome-wide analysis of HCC chromosomes by comparative genomic hybridization or loss of heterozygosity have identified more new loci implicated in hepatocarcinogenesis. Persistent hepatitis B is essential for inducing these mutations through immune-mediated injuries of the hepatocytes and the resulting hyperplasia. Prevention of hepatitis B by active immunization effectively interrupts persistent viral infections in children and subsequently reduces the risk of childhood HCC. Treatment for chronic hepatitis B by interferon or antiviral analogues can control hepatitis B activity, but its effect on controlling HCC remains to be seen. Insights for the hepatocarcinogenesis process should come from a multidisciplinary collaboration to explore important viral and host genes so that new approaches to diagnosis and treatment can be developed.

Animals↗

Seroepidemiologic survey for hepatitis B virus infection in Taiwan: the effect of hepatitis B mass immunization.

A hepatitis B mass immunization program was launched in Taiwan in July 1984, beginning with newborns of hepatitis B carrier mothers for the first 2 years of the program, which was then extended to all newborns. Seroepidemiology was studied in 3 cohorts at age 6 years. Each cohort consisted of 1500 children proportionally and randomly sampled from those entering elementary school in 1989, 1991, and 1993, representing those born 1 year before the program began and years 1 and 3 of the program, respectively. By RIA, the hepatitis B surface antigen positivity rates in the groups were 10.5%, 6.3%, and 1.7%, respectively; hepatitis B surface antibody positivity rates were 36.9%, 62.0%, 65.4%; and hepatitis B infection rates were 25.0%, 15.9%, 4.3%. Thus, universal immunization was more effective in reducing hepatitis B carriage than selective immunization of newborns of carrier mothers only. The program has proved effective in controlling chronic hepatitis B infection in Taiwan.

Biomarkers↗

GB virus C infection in hemodialysis patients: molecular evidence for nosocomial transmission.

Studies of the prevalence and clinical relevance of GB virus C (GBV-C) infection in 328 hemodialysis (HD) patients were done, and the possibility of nosocomial GBV-C transmission was explored by molecular epidemiology methods. For GBV-C viremic patients in a given HD unit, nucleotide sequences of the envelope region were analyzed by phylogenetic tree constructions. Of 328 HD patients, active hepatitis B virus, hepatitis C virus (HCV), and GBV-C infection were detected in 13%, 23%, and 17%, respectively. Except for a higher frequency of HCV coinfection, the demographic and clinical characteristics of patients with and without GBV-C infection were comparable. In contrast, patients with isolated HCV infection had significantly higher serum transaminase levels, longer time on HD, and more blood transfusions. Phylogenetic analysis showed several distinct clusters of closely related GBV-C isolates from one HD unit, suggesting the possibility of nosocomial transmission. These results suggest that GBV-C plays a minimal role in causing hepatitis in Taiwanese HD patients and in nosocomial transmission.

Adult↗

Bacterial infections associated with hepatic arteriography and transarterial embolization for hepatocellular carcinoma: a prospective study.

Sepsis and liver abscess are serious complications following transarterial embolization (TAE) for hepatocellular carcinoma (HCC). However, the exact incidence and the necessity of antibiotic prophylaxis remain undetermined. Between November 1996 and November 1997, we prospectively studied bacterial infections in 231 HCC patients who underwent 287 angiographic procedures without antibiotic prophylaxis, including 176 TAEs and 111 hepatic arteriographies (HAs). Four of the 111 HAs were complicated by transient asymptomatic bacteremia. Of the 176 TAEs, 2 were associated with asymptomatic bacteremia, and 7 (4%) were associated with symptomatic bacterial infection, including 3 cases of sepsis, 2 of liver abscess, and 2 of infected biloma. For patients with HCC, TAE was associated with a higher risk of developing symptomatic bacterial infections than was HA (4% vs. 0, respectively; P = .03). Previous gastrectomy was the only possible risk factor for liver abscess. Finally, early diagnosis and treatment of these infectious complications usually result in successful outcome.

Aged↗

Long term immune response of universal hepatitis B vaccination in infancy: a community-based study in Taiwan.

OBJECTIVES: To evaluate the long term immunity provided by a universal hepatitis B vaccination program in infancy and the booster effect on school age children who had no protective antibody titers to hepatitis B surface antigen. METHODS: We conducted a community-based seroepidemiologic study of 1337 healthy 7-year-old children in Taiwan one decade after the implementation of a mass hepatitis B vaccination program. A booster vaccination was suggested for noncarrier children who did not have protective titers of surface antibody. Serologic responses and infection rates were compared with those of the nonboostered children. In a nonselected group of 39 volunteer noncarrier vaccinees, quantitative serologic response was determined before, 1 month after a booster vaccination and 1 year later. RESULTS: A total of 572 children (42.8%) had low concentrations of surface antibody, and 9 were hepatitis B surface antigen carriers (0.7%). Eighty-two percent of "nonprotected" vaccinees showed immunologic memory to a booster dose and developed protective antibody titers 1 month later; 60.6% maintained protective titers 1 year later. The frequency of new hepatitis B virus infection was similar for those who received a booster and those who did not as investigated by the core antibody seroconversion during 1-year follow-up. However, the risk was low, with annual incidences of <1% in both groups, and none became chronic carriers. CONCLUSION: According to these data a universal vaccination program in infancy provides adequate protection against hepatitis B virus infection for school age children and a booster vaccination is not recommended.

Child↗

High frequency of expression of MAGE genes in human hepatocellular carcinoma.

AIMS/BACKGROUND: Activation of human MAGE genes leads to the expression of a set of tumor rejection antigens, which are recognized by cytotoxic T lymphocytes. The antigens may become the targets of immunotherapy. The expression of MAGE genes was originally found in, but is not restricted, to melanomas. The aim of this study was to investigate the expression of MAGE genes in human hepatocellular carcinomas. METHODS: The expression of MAGE-1, -2, -3, -4 genes in tumorous and corresponding non-tumorous liver tissue was studied using a reverse-transcription polymerase chain reaction. RESULTS: In the 50 hepatocellular carcinomas studied, MAGE-1, -2, -3, -4 mRNA expression was detected in 23 (46%), 17 (34%), 21 (42%) and 8 (16%), respectively. Seventy-four percent of the hepatocellular carcinomas expressed at least one of the MAGE genes. MAGE mRNAs were not detected in the corresponding non-tumor liver tissues. MAGE gene expression was not significantly correlated with clinicopathological factors. CONCLUSIONS: The MAGE genes are expressed in a high percentage of hepatocellular carcinomas; the MAGE gene products are potential targets for tumor-specific immunotherapy.

Adult↗

Characterization of the phosphorylated forms and the phosphorylated residues of hepatitis delta virus delta antigens.

Hepatitis delta virus (HDV) replication requires both the cellular RNA polymerase and one virus-encoded protein, small delta antigen (S-HDAg). S-HDAg has been shown to be a phosphoprotein, but its phosphorylation status is not yet clear. In this study, we employed three methods to address this question. A special two-dimensional gel electrophoresis, namely, nonequilibrium pH gradient electrophoresis, was used to separate the very basic S-HDAg. By carefully adjusting the pH of solubilization solution, the ampholyte composition, and the appropriate electrophoresis time periods, we were able to clearly resolve S-HDAg into two phosphorylated isoforms and one unphosphorylated form. In contrast, the viral large delta antigen (L-HDAg) can only be separated into one phosphorylated and one unphosphorylated form. By metabolic (32)P labeling, both immunoprecipitated S-HDAg and L-HDAg were found to incorporate radioactive phosphate. The extent of S-HDAg phosphorylation was increased upon 12-O-tetradecanoylphorbol-13-acetate treatment, while that of L-HDAg was not affected. Finally, phosphoamino acid analysis identified serine and threonine as the phospho residues in the labeled S-HDAg and only serine in the L-HDAg. Therefore, HDV S- and L-HDAgs differ in their phosphorylation patterns, which may account for their distinct biological functions.

Amino Acid Sequence↗

Molecular methods of measurement of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection: implications for occupational health practice.

Over the past decade, several molecular techniques for the detection of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) have been developed that have implications for occupational health practice. This review describes the techniques used for qualitative and quantitative detection of the viral genome, and briefly explains nucleic acid sequencing and analysis of phylogenetic trees. The review also discusses the current and potential uses of these techniques in investigations of transmission of bloodborne viruses by patient to worker and worker to patient, in the management of occupational exposure to blood, in research, and in the development of guidance and policy on infected healthcare workers who perform procedures prone to exposure.

DNA, Viral↗

Opportunistic hepatic infections in AIDS patients with fever of unknown origin.

The clinical features and histopathologic manifestations of hepatic opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS) in Taiwan remain unexplored. We report 28 AIDS patients (25 men, 3 women; mean age, 34 years) with fever of unknown origin who underwent 31 liver biopsies from December 1995 to May 1997. In most cases, the biochemical tests showed moderate to markedly elevated alkaline phosphatase concentrations, but normal or mildly elevated aminotransferase concentrations. The most common histopathologic finding was macrosteatosis, which was noted in 15 of the 28 patients. Another important histopathologic finding indicating the etiology of hepatic opportunistic infection was granuloma, which was found in 11 patients. Histochemical stain and culture of liver specimens yielded Mycobacterium avium complex (MAC) in eight patients, Mycobacterium tuberculosis in two patients, Histoplasma capsulatum in one patient, and cytomegalovirus in one patient with concomitant MAC infection. Therefore, a definitive diagnosis in AIDS patients with fever of unknown origin was made in 11 of the 28 cases with the assistance of liver biopsy. During follow-up, late extrahepatic involvement by the same infectious agents was found in six patients. Thus, hepatic manifestations could be a harbinger of disseminated opportunistic infections in AIDS patients.

AIDS-Related Opportunistic Infections↗

Tissue hepatocyte growth factor and proliferating cell nuclear antigen in hepatocellular carcinoma.

To better understand the roles of hepatocyte growth factor (HGF) and proliferating cell nuclear antigen (PCNA) in hepatocellular carcinoma (HCC), 37 surgically resected HCCs and corresponding nontumorous liver tissue specimens were collected and the expression of these two factors was quantified by Western blot analysis. Both HGF and PCNA expression levels were significantly higher in tumor tissue than in nontumorous liver tissue. However, their expression levels in HCC tissue and nontumorous tissue did not show any significant correlation with the recurrence of HCC. In addition, HGF and PCNA did not correlate with Edmondson's grade, invasiveness of tumor, presence of tumor capsule, or tumor size. No correlation was found between the expression levels of HGF and PCNA in HCC tissue. We conclude that, although both HGF and PCNA are present at higher levels in HCC tissue than in nontumorous liver tissue, they play little role in the clinicopathologic manifestations of this tumor. HGF appears to contribute little, if at all, to the proliferative activity of HCC cells.

Adult↗

[Compression of the deep branch of ulnar nerve at the wrist].

OBJECTIVE: To investigate the compression factor and clinical manifestation of the compression of deep branch of the ulnar nerve at the wrist. METHODS: Anatomic study was done on both sides of 10 cadavers, the deep branch of ulnar nerve, the Guyon's canal and the flexor digiti minimi brevis pedis were observed. Then from Jan. 1990 to Jan. 1997, 5 patients with compression of the deep branch of ulnar nerve at the wrist were treated clinically. Among them, there were 4 males and 1 female, aged from 37 to 48 years and the course of disease ranged from 1 to 5 months. RESULTS: The motor branch of the ulnar nerve passed under the tendinous arcade of flexor digiti minimi brevis pedis. Occasionally, the branch of ulnar artery overpassed the motor branch. Clinically, the tendinous arcade compressed the motor branch was released, and after 2 to 4 years follow-up, the clinical results were satisfactory. CONCLUSION: The main compression factor of the ulnar nerve at the wrist is the tendinous arcade of the flexor digiti minimi brevis pedis, the tendinous arcade should be released sufficiently during the operation.

Adult↗

An ELISA for RNA helicase activity: application as an assay of the NS3 helicase of hepatitis C virus.

A convenient enzyme-linked immunosorbent assay (ELISA) for RNA helicase activity was developed with principles similar to the standard assay. The helicase ELISA utilizes a non-radioactive double-stranded substrate with a biotin-labeled template (long) strand hybridized to a digoxigenin (DIG)-labeled release (short) strand. The template strand binds to the wells of streptavidin-coated microtiter plates (SA-MTP) where the helicase catalyzes the unwinding reaction. Substrate not unwound retains the DIG-labeled release strand and is detected using anti-DIG coupled to horseradish peroxidase. Chromogenic detection follows. Absorbance measurement allows determination of unwinding efficiency of reactions. To demonstrate effectiveness, the ELISA-based assay was used to study the unwinding activity of the hepatitis C virus (HCV) NS3 helicase. Using a known inhibitor of NS3 helicase activity and two mutant HCV helicases, the ability of the assay to screen potential anti-helicase drugs and putative helicases is illustrated. The helicase ELISA is more convenient than the standard helicase assay and is especially suited for the testing of large numbers of samples.

Catalytic Domain↗