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Biomedical subjects

D S Chen

Publications and source records attributed to D S Chen.

At least 19 recordsLinked to original sources
PubMed2001

Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination.

BACKGROUND: Hepatitis B virus (HBV) infection is hyperendemic in Taiwan. Before universal HBV immunization was started in Taiwan in 1984, the carrier rate for hepatitis B surface antigen (HBsAg) was 15% to 20% in the general population. OBJECTIVE: To quantify the population impact of a mass vaccination program for HBV 15 years after its implementation. DESIGN: Descriptive analysis of serologic markers of HBV in healthy children and adolescents. SETTING: Chung-Cheng District, Taipei City, Taiwan, in 1999. PARTICIPANTS: 1357 persons younger than 15 years of age, who were born after the implementation of universal HBV vaccination, and 559 persons 15 to 20 years of age, who were born before the program began. MEASUREMENTS: Repeated serologic surveys similar to those done before and 5 and 10 years after the national vaccination program was implemented. All participants were tested for serum HBsAg, its antibody (anti-HBs), and hepatitis B core antibody (anti-HBc). RESULTS: During the 15 years since the vaccination program was implemented, the prevalence of HBsAg among persons younger than 15 years of age decreased from 9.8% in 1984 to 0.7% in 1999; among persons 15 to 20 years of age, the 1999 prevalence of HBsAg was 7% (P < 0.001). Hepatitis B core antibody seropositivity, which represents HBV infection, was found in 2.9% of persons younger than 15 years of age and in 20.6% of persons 15 to 20 years of age (P < 0.001); in the same age groups, the rate of anti-HBs seropositivity was 75.8% and 70.7%, respectively (P = 0.02). CONCLUSIONS: Universal vaccination significantly decreased the HBV carrier rate and infection rate among children and adolescents born since the program began. By decreasing the carrier pool, continuation of the national HBV immunization program should prevent HBV infection in the children of Taiwan, and, subsequently, adults as well.

Female↗
PubMed2001

Efficacy of a mass hepatitis B immunization program after switching to recombinant hepatitis B vaccine: a population-based study in Taiwan.

To study the efficacy of immunization against hepatitis B after plasma-derived vaccine was replaced by recombinant vaccine, 2-year-old Taiwanese children were recruited by stratification random sampling and tested for hepatitis B markers. They were grouped according to maternal infectivity and children's immunization status. Of 2010 children, 2.5% had hepatitis B surface antigen (HBsAg), 94.1% had its antibody (anti-HBs), 6.8% had core antibody, and 3.3% were seronegative. Children of highly infectious mothers immunized with hepatitis B immunoglobulin and vaccine on schedule had a lower HBsAg-positive rate and a higher anti-HBs-positive rate than those with vaccine only and off-schedule. The efficacy of the Taiwanese mass hepatitis B immunization was maintained after switching to recombinant hepatitis B vaccine.

Child, Preschool↗
PubMed2001

Expressions of cancer-testis antigens in human hepatocellular carcinomas.

Though regular sonographic examination can early detect small hepatocellular carcinoma, the therapeutic results remains unsatisfactory. Antigen-specific immunotherapy is an alternative approach for controlling tumors. The prerequisite for antigen-specific cancer immunotherapy is the identification of appropriate tumor antigens. Recently, a new category of tumor-specific shared antigens, called cancer-testis antigens, has been identified. The cancer-testis antigens have been found in a variety of cancers. However, the expression of cancer-testis antigens in human hepatocellular carcinomas is unknown. The aim of this current study is to investigate the expression of cancer-testis antigens in human hepatocellular carcinomas. Reverse-transcription polymerase chain reaction (RT-PCR) was used to investigate the expression of the SSX-1,-2,-4,-5, SCP-1, NY-ESO-1 genes in tumorous and corresponding non-tumorous liver tissues. In the 30 hepatocellular carcinomas studied, SSX-1,-2,-4,-5, SCP-1, and NY-ESO-1 mRNA expressions were detected in 24 (80%), 14 (46.7%), 22 (73.3%), 10 (33.3%), 2 (6.7%), and 11 (36.7%), respectively. Expressions of these genes were detected in few non-tumor liver tissues. The cancer-testis antigens are expressed in a high percentage of hepatocellular carcinomas. These cancer-testis antigen gene products are potential targets for antigen-specific immunotherapy of hepatocellular carcinoma.

Adult↗
PubMed2001

Post-partum acute exacerbation of chronic hepatitis in a hepatitis C-carrier mother.

Hepatitis C virus infection is a global health problem; however, the interaction between pregnancy and chronic hepatitis C remains controversial. A Taiwanese woman with chronic hepatitis C had an uncomplicated pregnancy and gave birth to a female baby through spontaneous vaginal delivery. The serum levels of alanine aminotransferase and hepatitis C virus (HCV) RNA were measured before pregnancy, in the first and third trimesters, 1 and 3 months after delivery, respectively. During her pregnancy, the serum aminotransferase levels became normalized, while the serum HCV-RNA levels declined significantly and consecutively with the lowest viral load in the third trimester. One month after delivery, she had an abrupt elevation of serum HCV-RNA level, paralleling a hepatitis flare with serum aminotransferase level more than 20-fold the upper normal limit. The serum HCV-RNA levels declined thereafter, and serum aminotransferase levels became normalized 3 months postdelivery. She was infected with HCV genotype 1a throughout the entire follow-up period, and other causes of hepatitis flare were excluded. In conclusion, post-partum acute exacerbation of chronic hepatitis may occur in HCV-carrier mothers, and an abrupt elevation of serum HCV-RNA level may be associated with the acute exacerbation.

Acute Disease↗
PubMed2001

Lamivudine treatment for hepatitis B reactivation in HBsAg carriers after organ transplantation: a 4-year experience.

BACKGROUND: Reactivation of hepatitis B after organ transplantation in hepatitis B surface antigen (HBsAg) carriers may be fatal. In this study, we reported our experience of lamivudine treatment in HBsAg carriers who had post-transplant reactivation of hepatitis B. METHODS: The patients were 15 men and one woman. Nine received kidney transplants, six received heart transplants, and one received a lung transplant. They developed a reactivation of hepatitis B 1-101 months (median, 14 months) after transplantation. They received lamivudine 100 mg daily on a compassionate-use basis, and had regular follow ups. The median pretreatment total serum bilirubin level was 3.0 mg/dL, and the alanine aminotransferase level was 357 U/L. Four of the 16 patients were positive for HBeAg. The serum hepatitis B virus (HBV) DNA levels were > 3000 pg/mL in 13 (81%) patients. Three were coinfected with hepatitis C virus. RESULTS: The overall survival rate was 75%. All four fatal cases had a pretreatment total serum bilirubin level of > or = 3 mg/dL. Serum HBV-DNA soon became undetectable in 12 survivors. Of the 12 survivors, after a median treatment period of 101 weeks, a lamivudine-resistant strain with variation in the YMDD motif of the HBV polymerase gene developed in three (25%). None had significant adverse reactions to lamivudine treatment. CONCLUSIONS: These results indicated that lamivudine is effective in the treatment of post-transplant hepatitis B reactivation, including patients with dual chronic hepatitis B and C. Early recognition of HBV reactivation and prompt lamivudine treatment are important to prevent mortality.

Adult↗
PubMed2001

Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma.

BACKGROUND & AIMS: Cirrhotic nodules have long been assumed to be the precancerous lesions of hepatocellular carcinoma (HCC). We thus investigated the allelic imbalance (AI) in cirrhotic nodules to define the genetic aberrations in early hepatocarcinogenesis. METHODS: One hundred eighty cirrhotic nodules from 7 female patients with HCC were collected by microdissection. Their clonality nature was assessed by examining the X chromosome methylation pattern. AI in monoclonal cirrhotic nodules and the corresponding HCCs were analyzed with microsatellite polymorphic markers. RESULTS: One hundred one out of 180 nodules (56.1%) were monoclonal and the average fractional AI (FAI) was 21%, lower than the 40% in HCC. Their overall AI patterns differed significantly from that in HCC (P < 0.001) with FAI on 2q, 4q, 8p, and Xq higher than the mean value. Comparison of FAI in nodules (stratified by increasing total AI events) further revealed a progressive increase of FAI on 4q, 8p, and Xq. In contrast, FAI on 1p, 13q, 16q, and 17p were low in nodules but rose above the mean only in HCC. CONCLUSIONS: About half of the cirrhotic nodules are monoclonal and already have chromosome aberrations. AI on 4q, 8p, and Xq may be the earlier mutations, whereas AI on 1p, 13q, 16q, and 17p occurs late in hepatocarcinogenesis.

Adult↗
PubMed2001

Hepatitis B virus variants in patients receiving lamivudine treatment with breakthrough hepatitis evaluated by serial viral loads and full-length viral sequences.

Both viral loads and genome variations have been implicated in the pathogenesis of acute exacerbation of chronic hepatitis B. Hepatitis B exacerbation in patients receiving lamivudine treatment represented a unique setting to clarify their importance. Three organ recipients with posttransplantation hepatitis B exacerbation and 3 patients with chronic hepatitis B were studied. All received lamivudine treatment and their alanine aminotransferase (ALT) levels and hepatitis B virus (HBV) loads were regularly followed. Full-length genomic sequences before and during lamivudine treatment were determined in patients who had breakthrough of serum HBV DNA or elevation of serum ALT. Breakthrough of serum HBV DNA occurred after 6 to 15 months of lamivudine treatment in all. A rapid increase of viral load accompanying the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) variant was followed by hepatitis B exacerbation in each patient. The mean number of nucleotide and amino acid substitutions per genome pair was equivalent in immunosuppressed or immunocompetent patients (6.3 vs. 6.3 for nucleotide, P >.05; 6.0 vs. 6.7 for amino acid, P >.05). Changes of nucleotide and amino acid beyond the YMDD motif were distributed along the whole HBV genome but none occurred within the known B-cell epitopes and human leukocyte antigen class I- or II-restricted T-cell epitopes. Our results suggest that a resurgence of viral load rather than changes of the known immunogenic viral epitopes is more closely associated with the development of hepatitis B exacerbation after the emergence of YMDD variants in patients receiving lamivudine treatment.

Adult↗
PubMed2001

Acute exacerbations of chronic hepatitis B are rarely associated with superinfection of hepatitis B virus.

There are 7 genotypes of hepatitis B virus (HBV). Whether superinfection of HBV carriers with different HBV genotypes occurs remains unknown. We therefore determined the HBV genotype and association between superinfection and acute exacerbation of disease in a cohort of 244 patients with chronic HBV infection who had elevated serum aminotransferase levels for at least 1 year. Within this group, 103 patients experienced acute exacerbation with an annual incidence of 13%, and 20 of the 103 patients had IgM antibody to hepatitis B core antigen (IgM anti-HBc). These 20 patients had a higher prevalence of genotype C infection (65%) than the remaining 83 anti-core IgM-negative patients (40%) who also had acute exacerbations (P <.05). Detailed analysis of HBV genotypes and sequences of the variable pre-S gene were determined in serial samples from 20 patients with IgM anti-HBc-positive acute exacerbations (group A), 20 patients with IgM anti-HBc-negative acute exacerbations (group B), and 20 patients without exacerbations (group C). Two (10%) of the group A patients had virologic evidence of HBV superinfection during acute exacerbation, one superinfected with heterotypic virus and the other with homotypic virus. The newly introduced virus disappeared after the exacerbation and the original virus resumed thereafter. The calculated prevalence of HBV superinfection in the hepatitis B carriers and those with acute exacerbations was 0.8% (2 of 244) and 1.9% (2 of 103), respectively. In conclusion, superinfection of HBV on hepatitis B carriers indeed occurs and may cause acute exacerbations, albeit at a low frequency even in hyperendemic areas of HBV infection.

Adolescent↗
PubMed2001

Universal hepatitis B vaccination and the decreased mortality from fulminant hepatitis in infants in Taiwan.

OBJECTIVES: To assess the annual mortality rate associated with fulminant hepatitis in infants before and after the mass immunization program that was launched in Taiwan in July 1984. STUDY DESIGN: From the National Mortality Registry System, the data on the mortality from fulminant hepatitis in infants from 1975 to 1998 were retrieved. Poisson regression analysis was used to assess the difference in average mortality from fulminant hepatitis in infants before (1975-1984) and after (1985-1998) the implementation of the mass hepatitis B vaccination program. RESULTS: The ratio of yearly mortality from 1975 to 1998 was 1.10 (P <.001), representing a progressive decrease in the number of the cases. The average mortality associated with fulminant hepatitis in infants from 1975 to 1984 and from 1985 to 1998 was 5.36 and 1.71 per 100,000 infants, respectively. The ratio of the average mortality in the period from 1985 to 1998 to that in the period from 1975 to 1984 was 0.32 (P <.001). CONCLUSIONS: These data indicate that since the institution of a program of mass hepatitis B vaccination in Taiwan, the mortality associated with fulminant hepatitis in infants has declined significantly.

Hepatitis B Surface Antigens↗
PubMed2001

Amebic liver abscess and human immunodeficiency virus infection: a report of three cases.

Invasive amebiasis rarely occurs in homosexual men and human immunodeficiency virus (HIV)-infected individuals and has not been regarded as a beacon for concomitant HIV infection. We encountered a bisexual man with a protracted course of amebic liver abscess and amebic colitis. In the presence of fever, generalized lymphadenopathy, and elevated serum aminotransferase levels, HIV infection was suspected and then confirmed by a de novo seroconversion of HIV antibody. Subsequently, we noted two consecutive patients with amebic liver abscess, also later found to be infected with HIV. The ameba obtained from these three cases was identified as Entamoeba histolytica by amplification of 16S ribosomal RNA by polymerase chain reaction and direct sequencing. This observation suggests that amebic liver abscess and colitis can be presentations for HIV infection in the Far East. Thus, the local patients with invasive amebiasis, especially those with a protracted course or with risk factors of HIV infection, should be tested for HIV.

AIDS-Related Opportunistic Infections↗
PubMed2001

Functional measurement of hepatitis C virus core-specific CD8(+) T-cell responses in the livers or peripheral blood of patients by using autologous peripheral blood mononuclear cells as targets or stimulators.

As is widely recognized, CD8(+) cytotoxic T lymphocytes (CTLs) play a crucial role in hepatitis C virus (HCV) infection, both in pathogenesis of liver injury and in clearing the virus. CTL studies with HCV-infected patients have been difficult because of the relatively low frequency of CTL precursors in the peripheral blood and because the targeted epitopes vary depending on the human leukocyte antigen (HLA) types of the individuals. This study attempts to overcome these problems by assessing the feasibility of using autologous peripheral blood mononuclear cells (PBMCs) expressing viral antigens as stimulators or targets in order to monitor the CTL responses. Primary PBMCs were transduced using a retroviral vector pseudotyped with a vesicular stomatitis virus G glycoprotein expressing the HCV core gene. Additionally, the vector-transduced PBMCs were used as targets of CTL assays to measure the HCV core-specific CTL activities from the liver-infiltrating lymphocytes of six different HLA-type patients with chronic HCV infection. The core-expressing PBMCs also served as stimulators, allowing us to measure core-specific CD8(+) T-cell responses by intracellular gamma interferon staining of the peripheral blood of hepatitis C patients who had received treatment with alpha interferon plus ribavirin. This approach provides an efficient means of measuring antigen-specific CTL responses without HLA constraints.

Autoantigens↗
PubMed2001

Structure-based mutational analysis of the hepatitis C virus NS3 helicase.

The carboxyl terminus of the hepatitis C virus (HCV) nonstructural protein 3 (NS3) possesses ATP-dependent RNA helicase activity. Based on the conserved sequence motifs and the crystal structures of the helicase domain, 17 mutants of the HCV NS3 helicase were generated. The ATP hydrolysis, RNA binding, and RNA unwinding activities of the mutant proteins were examined in vitro to determine the functional role of the mutated residues. The data revealed that Lys-210 in the Walker A motif and Asp-290, Glu-291, and His-293 in the Walker B motif were crucial to ATPase activity and that Thr-322 and Thr-324 in motif III and Arg-461 in motif VI significantly influenced ATPase activity. When the pairing between His-293 and Gln-460, referred to as gatekeepers, was replaced with the Asp-293/His-460 pair, which makes the NS3 helicase more like the DEAD helicase subgroup, ATPase activity was not restored. It thus indicated that the whole microenvironment surrounding the gatekeepers, rather than the residues per se, was important to the enzymatic activities. Arg-461 and Trp-501 are important residues for RNA binding, while Val-432 may only play a coadjutant role. The data demonstrated that RNA helicase activity was possibly abolished by the loss of ATPase activity or by reduced RNA binding activity. Nevertheless, a low threshold level of ATPase activity was found sufficient for helicase activity. Results in this study provide a valuable reference for efforts under way to develop anti-HCV therapeutic drugs targeting NS3.

Adenosine Triphosphatases↗
PubMed2001

The conserved serine 177 in the delta antigen of hepatitis delta virus is one putative phosphorylation site and is required for efficient viral RNA replication.

Hepatitis delta virus (HDV) small delta antigen (S-HDAg) plays a critical role in virus replication. We previously demonstrated that the S-HDAg phosphorylation occurs on both serine and threonine residues. However, their biological significance and the exact phosphorylation sites of S-HDAg are still unknown. In this study, phosphorylated S-HDAg was detected only in the intracellular compartment, not in viral particles. In addition, the number of phosphorylated isoforms of S-HDAg significantly increased with the extent of viral replication in transfection system. Site-directed mutagenesis showed that alanine replacement of serine 177, which is conserved among all the known HDV strains, resulted in reduced phosphorylation of S-HDAg, while the mutation of the other two conserved serine residues (2 and 123) had little effect. The S177A mutant dramatically decreased its capability in assisting HDV RNA replication, with a preferential and profound impairment of the antigenomic RNA replication. Furthermore, the viral RNA editing, a step relying upon antigenomic RNA replication, was also abolished by this mutation. These results suggested that phosphorylation of S-HDAg, with serine 177 as a presumable site, plays a critical role in viral RNA replication, especially in augmenting the replication of antigenomic RNA.

Amino Acid Sequence↗
PubMed2001

[Anatomical study and clinical application of long head of triceps muscle for reconstruction of shoulder abduction].

OBJECTIVE: To study the morphological character of long head of triceps muscle for clinical application in reconstruction of shoulder abduction. METHODS: Forty-four upper extremities of fixed human adult cadavers were carefully dissected. The origins and the pedicles of blood vessels and nerves of long head of triceps muscle, as well as the maximum available size of the muscles, were measured. Six cases of clinical application of long head of triceps muscle for reconstruction of shoulder abduction were followed up for 3 to 11 months. RESULTS: The origins in the dorsal side of long head of triceps muscle were muscular and the ventral side were tendinous, which was 7.6 to 13.3 cm in length and 1.6 to 3.4 cm in width. The distance from the origin to the neurovascular pedicle was 5.7 to 11.4 cm. The radial nerve, which innervated the muscles, could be dissected for 2.9 to 11.8 cm in length. The blood supplies to the triceps muscle were from humeral artery (43.2%), 1.0 to 6.0 cm in length and 1.6 to 2.4 mm in diameter, and from humeral profundus artery (45.5%), 1.5 to 4.4 cm in length and 0.9 to 2.4 mm in diameter, if the vessel was separated to the humeral artery, the length was 1.5 to 6.3 cm. The neurovascular pedicles were multiple branched. In the 6 cases of clinical application of the triceps muscles, the operated shoulder could abduct from 5 degrees preoperatively (0 degree to 10 degrees) to 77.3 degrees (50 degrees to 90 degrees) postoperatively. CONCLUSION: In accordance to the anatomical character of the triceps muscles, the long head of triceps muscle is a suitable choice for reconstruction of shoulder abduction with optimistic outcomes.

Adolescent↗
PubMed2001

Molecular cloning and expression of woodchuck granulocyte-macrophage colony stimulating factor.

Granulocyte-macrophage colony stimulating factor (GM-CSF) has immunoregulatory and antiviral effects, and may thus be promising for the treatment of chronic hepatitis B. Using woodchuck hepatitis virus (WHV)-infected woodchuck as an animal model to test the efficacy and safety of GM-CSF on the therapy of chronic hepatitis B, woodchuck GM-CSF will be required due to the apparent species-specific activity of GM-CSF. The cDNA of woodchuck GM-CSF was cloned using reverse transcription-polymerase chain reaction (RT-PCR) with primers deriving from highly conserved regions of GM-CSF genes from other species. The deduced amino acids, including the signal peptide, is 138 in length and its identities to human, murine, canine and bovine GM-CSFs are 63, 49, 63, and 63% respectively. The genomic DNA of woodchuck GM-CSF was also cloned by PCR. Its organization is highly homologous to that of human and murine GM-CSF genes, consisting of four exons and three introns. Cloned woodchuck GM-CSF was expressed transiently in 293T cells. The recombinant protein expressed was found to stimulate the growth and differentiation of woodchuck bone marrow cells, indicating the protein expressed by the cloned gene is functional. These results pave the way for future studies on the potential role of GM-CSF for the treatment of chronic hepatitis B by using this animal model.

Amino Acid Sequence↗
PubMed2001

Prolonged interferon treatment after combination interferon and ribavirin therapy in patients with chronic hepatitis C: a clinical trial of interferon relapsers and non-responders.

BACKGROUND AND PURPOSE: For the retreatment of chronic hepatitis C patients relapsing after, or non-responsive to, previous interferon therapy, the efficacy of combination therapy with interferon alfa plus ribavirin is superior to interferon alone. The aim of this study was to determine whether prolonged interferon alfa treatment after 24-week combination therapy can further increase the efficacy of combination therapy. METHODS: Nineteen interferon relapsers and 17 interferon non-responders were randomly assigned to receive either interferon alfa 5 million units (MU) thrice weekly plus oral ribavirin 1,200 mg daily for 24 weeks (regimen A) or interferon alfa 5 MU thrice weekly plus oral ribavirin 1,200 mg daily for 24 weeks followed by interferon alfa 3 MU thrice weekly for another 24 weeks (regimen B). Efficacy was assessed by normalization of serum aminotransferase concentrations and disappearance of serum hepatitis C virus (HCV) RNA at the end of treatment and at 24 weeks after stopping treatment. RESULTS: Overall, 67% of relapsers receiving regimen A and 80% of those receiving regimen B had sustained virologic responses 24 weeks after stopping treatment. In contrast, 45% of non-responders receiving regimen A and 63% of those receiving regimen B had sustained responses. The sustained response was more common in relapsers with non-1b HCV genotypes. The sustained response rate to combination therapy was 50% or more in patients with genotype 1b infection. CONCLUSIONS: Prolonged interferon treatment after combination therapy has a comparable efficacy to combination therapy alone for the retreatment of chronic hepatitis C patients relapsing after, or non-responsive to, previous interferon therapy.

Adult↗
PubMed2000

Hepatitis B vaccination and hepatocellular carcinoma rates in boys and girls.

CONTEXT: Hepatocellular carcinoma (HCC) has a male predominance and is closely related to hepatitis B virus (HBV) infection. Hepatitis B virus vaccination was launched in 1984 in Taiwan for neonates of mothers carrying hepatitis B e antigen, resulting in a decreased incidence of HCC in children. The effect on boys vs girls is not known. OBJECTIVE: To evaluate the association between a HBV vaccination program with incidence of childhood HCC by sex. DESIGN AND SETTING: Analysis of data collected from Taiwan's National Cancer Registry System and the Taiwan Childhood Hepatoma Study Group between 1981 and 1996. PARTICIPANTS: Children aged 6 to 14 years who were diagnosed as having HCC (201 boys and 70 girls). MAIN OUTCOME MEASURE: Incidence of HCC in boys and girls before and after implementation of the vaccination program. RESULTS: The boy-girl incidence ratio decreased steadily from 4.5 in 1981-1984 (before the program's introduction) to 1.9 in 1990-1996 (6-12 years after the vaccination program was launched). The incidence of HCC in boys born after 1984 was significantly reduced in comparison with those born before 1978 (relative risk [RR], 0.72; P =.002). No significant decrease in HCC incidence was observed in girls born in the same periods (RR, 0.77; P =.20). The incidence of HCC in boys remained stable with increasing age, while an increase of HCC incidence with age in girls was observed. These age and sex effects remained the same regardless of birth before or after the vaccination program. CONCLUSION: Our results suggest that boys may benefit more from HBV vaccination than girls in the prevention of HCC.

Adolescent↗