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Biomedical subjects

D S Chen

Publications and source records attributed to D S Chen.

At least 109 records · Page 6Linked to original sources
PubMed1997

Positive and negative strand of hepatitis C virus RNA sequences in peripheral blood mononuclear cells in patients with chronic hepatitis C: no correlation with viral genotypes 1b, 2a, and 2b.

Hepatitis C virus (HCV) has many genotypes which are closely associated with the severity of chronic hepatitis and the response to antiviral therapy. Although HCV is essentially hepatotropic, several lines of evidence suggest that this virus can infect peripheral blood mononuclear cells (PBMC) in most patients with chronic HCV infection. However, the methods used previously to detect negative-strand HCV RNA have been questioned, and the PBMC tropism of different HCV genotypes remains unknown. A stringent method was used to investigate the prevalence of positive- and negative-strand HCV RNA in the PBMC of 106 patients with chronic hepatitis C and to analyze the influence of HCV genotype on the tropism of PBMC. HCV type 1b was the predominant strain in the patients. Positive-strand RNA in PBMC was detected in 83 (78%) and 40% had negative-strand RNA. The demographic and clinical features were comparable among different patients grouped by the replication status of HCV in the plasma and PBMC samples. In addition, there was no significant difference of PBMC tropism between type 1b and non-1b HCV. In summary, HCV does indeed infect actively the PBMC of chronic hepatitis C patients and such infection is not correlated to the pathogenesis of liver cell damage. Moreover, the genotype is not associated specifically with PBMC tropism of HCV.

Adult↗
PubMed1997

GB virus-C/hepatitis G virus infection in prostitutes: possible role of sexual transmission.

The modes of transmission of GB virus-C/hepatitis G virus (GBV-C/HGV) other than by blood transfusion are largely unknown. The prevalence of GBV-C/HGV viremia and the associated risk factors in 145 female prostitutes were examined. The seroprevalence of hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), and GBV-C/HGV RNA were 14%, 18%, and 11%, respectively. The demographic characteristics were similar between subjects with and without HBsAg. In contrast, those with HCV or GBV-C/HGV infection had practised longer as prostitutes and received blood transfusion more frequently. Moreover, the prevalence of GBV-C/HGV RNA and anti-HCV tended to increase in parallel with the duration of prostitution. These results suggest that like HCV, sexual transmission of GBV-C/HGV occurs and the risk increased with prolonged duration of exposure. The transmission efficiency between GBV-C/HGV and HCV appears to be similar.

Adult↗
PubMed1997

Characterization of Ca(2+)- and voltage-dependent nonselective cation channels in human HepG2 cells.

Nonselective cation channels have been identified and linked to important cell functions in rat hepatocytes. In this study, we characterized inward rectifying nonselective cation channels in detail by the patch clamp technique in human HepG2 cells. Channel properties were studied with high resistance borosilicate pipettes in cell-attached and inside-out configurations. With Ringer's solution and KCl as pipette solutions, the conductances were 19.7 +/- 2.1 and 22.2 +/- 0.0 picosiemens (pS), and reversal potentials were 30.9 +/- 3.5 and 31.3 +/- 4.6 mV, respectively. The channel was permeable to Ba2+, and the sequence of permeability ratios was Na+ > K+ > Cs+ > Ba2+. In the cell-attached configuration, the channel had a higher opening probability at depolarizing potential than at hyperpolarizing. In the inside-out patches with symmetric Ringer's solution, the current voltage curve was linear with conductance of 19.8 +/- 0.9 pS. Reversal potential shifted from -0.2 +/- 1.0 mV to 23.2 +/- 1.0 mV when the bath solution was replaced by dilute Ringer's solution. In the inside-out configuration, the gating was Ca(2+)-dependent, and the opening probability increased with increasing intracellular calcium concentration ([Ca2+]i). An outward rectifying channel appeared when [Ca2+]i was less than 1 mumol/L. The nonselective channel was reversibly blocked by 10 mumol/L internal flufenamic acid. We conclude that Ca(2+)- and voltage-dependent nonselective cation channels are present in human HepG2 cells. The channels might be involved in the regulation of Ca2+ influx and are associated with activation of other ion channels.

Animals↗
PubMed1997

Immunoglobulin M antibody response to hepatitis C virus core protein in patients with chronic hepatitis C.

We retrospectively assessed the frequency and clinicopathologic and virologic significance of production of immunoglobulin M (IgM) antibody to hepatitis C virus (HCV) core protein in patients with chronic hepatitis C. Sera from 60 patients with chronic hepatitis C were tested for IgM anti-HCVcore (anti-HCc). Twenty of these patients received ribavirin plus interferon-alpha for 24 weeks, and were classified as sustained, transient, or nonresponders on the basis of alanine aminotransferase levels and the presence of HCV RNA at the end of treatment and 24 weeks later. IgM anti-HCc was detected in 21 patients. There was no correlation between the presence of IgM anti-HCc and clinical features such as sex, age, mode of transmission, serum levels of alanine aminotransferase, HCV genotype, serum HCV titer, or histologic findings. Among the patients who received ribavirin plus interferon-alpha, the mean IgM anti-HCc level before therapy was comparable between sustained (n = 10), transient (n = 8), and nonresponders (n = 2). A statistically significant decrease in IgM anti-HCc response during antiviral therapy was observed in the 18 responders who became negative for serum HCV RNA at the end of therapy. These data suggest that IgM anti-HCc is of limited clinical usefulness as a marker of chronic HCV infection. Serial testing for IgM anti-HCc may provide a marker of antiviral response.

Adult↗
PubMed1997

Clinical and microbiological features of liver abscess after transarterial embolization for hepatocellular carcinoma.

OBJECTIVES: To present the clinical and microbiological features of liver abscess after transarterial embolization (TAE) for hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed records of 452 TAE procedures in 289 patients with HCC over a 2-yr period. RESULTS: Four men and one woman with a mean age of 68.4 yr were diagnosed with liver abscess 1-8 wk (mean 4.6 wk) after the embolization. The incidence was 1.1% (5/452). Common symptoms included fever, chills, and right upper quadrant pain. Serum aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase levels and leukocyte count were frequently elevated. All the abscesses appeared as areas of hypodensity on CT scan and hypoechogenicity on ultrasonogram. The areas contained gas in the embolized tumor, which led to the suspicion and finally the diagnosis of abscess. In contrast to predominance of gram-negative aerobes in sporadic pyogenic liver abscesses, the causative microorganism was predominantly gram positive (60%). All patients were treated with parenteral antibiotics plus percutaneous aspiration, drainage, or operation, but one patient died from the abscess. CONCLUSIONS: For patients receiving TAE for HCC, few specific clinical or radiological features could readily differentiate patients complicated with liver abscess from those without. This may delay a timely diagnosis and lead to significant morbidity. Hence, in patients with risk factors, including old age, previous biliary tract disease, large tumor size (>5 cm), and gas forming in the embolized tumor, aspiration of the suspected focal hepatic lesion should be performed as soon as possible.

Abdominal Pain↗
PubMed1997

Interspousal transmission of GB virus-C/hepatitis G virus: a comparison with hepatitis C virus.

Although infection with GB virus-C/hepatitis G virus (GBV-C/HGV) by blood transfusion is well documented, little is known about the other routes of transmission. The prevalence of GBV-C/HGV infection in spouses of index patients and the related risk factors were studied. Hepatitis C virus (HCV) and GBV-C/HGV infections were studied in spouses of 100 patients with hepatitis C, of whom 12 were found to be also positive for GBV-C/HGV RNA. For couples both with GBV-C/ HGV viremia, nucleotide sequences of the divergent envelope region were analyzed by phylogenetic tree constructions. For HCV infection, anti-HCV was found in 14 (14%) of the 100 spouses. Five spouses (42%) of the 12 patients with dual infection of GBV-C/HGV and HCV had evidence of GBV-C/HGV infection, three had viral RNA, and two had antibodies to a recombinant HGV envelope protein E2. Nucleotide sequence comparison and phylogenetic tree analysis of the genome in the GBV-C/HGV infected couple revealed the isolates to be closely related. These results suggest that spouses of patients with GBV-C/HGV infection are at a higher risk of acquiring GBV-C/HGV as compared with HCV, and they should be educated to avoid GBV-C/HGV infection from their spouses, in case GBV-C/HGV is shown to be pathogenic.

Adenovirus E2 Proteins↗
PubMed1997

Detection of hepatic neoplasms by computed tomographic arterial portography in cirrhotic patients.

Computed tomography (CT) during arterial portography (CTAP) is useful in detecting hepatic tumors but cirrhotic change may interfere with portal flow and the prediction of resectability. We evaluated the usefulness of CTAP in detecting hepatic tumors, especially hepatocellular carcinoma (HCC), in patients with or without cirrhotic change. Ninety-six patients with pathologically proven hepatic tumors were assessed, of whom 90 had hepatocellular carcinoma. The tumors had been previously detected by abdominal ultrasound and CT scans, after which the patients were referred for angiography and CTAP. The CTAP findings were compared with ultrasonographic, conventional CT, angiographic, and subsequent surgical and pathologic findings regarding size, number, and location of the hepatic lesions. CTAP detected 134 of 143 pathologically proven lesions. The overall sensitivity of CTAP in the 96 patients was 94%, with a false-positive rate of 22%. The detection rate of CTAP for tumors less than 2 cm in diameter was high (92%). The sensitivity and false-positive rate for CTAP in 60 cirrhotic patients were 94% and 23%, respectively, CTAP is a sensitive imaging modality for detection of hepatic neoplasms even in patients with cirrhosis, but its false-positive rate is high.

Adult↗
PubMed1996

Seroepidemiology of hepatitis B virus infection in children: Ten years of mass vaccination in Taiwan.

OBJECTIVE: To study the seroepidemiology of hepatitis B virus (HBV) infection in children 10 years after a mass hepatitis B vaccination program was begun in Taiwan. DESIGN: Cross-sectional seroprevalence survey. SETTING: Cheng-Chung/Chung-Cheng District, Taipei, Taiwan, 1994. SUBJECTS AND METHODS: Serum samples from 1515 healthy children younger than 12 years were tested for HBV markers. The results were compared with a baseline seroepidemiologic study conducted just before the vaccination program was launched in 1984 and with a subsequent study in 1989 in the same area. MAIN RESULTS: Eighty-seven percent of the children had received at least 3 doses of HBV vaccine. The overall prevalence rate of hepatitis B surface antigenemia decreased from 9.8% in 1984 to 1.3% in 1994. A statistically significant decrease was observed in every age group from 1 to 10 years. The overall prevalence rate of hepatitis B core antibody was 26% in 1984, 15% in 1989, and 4.0% in 1994. This suggests that the risk of horizontal HBV infection has decreased over time, not only because of the protective effect of the vaccine but also because the infection source has diminished. A high prevalence rate of hepatitis B surface antibody (79%) was noted in 1994 as anticipated. CONCLUSIONS: The Taiwanese mass vaccination program has protected most children younger than 10 years from becoming carriers, reducing both perinatal and horizontal HBV transmission. Mass HBV vaccination has proved to be a successful method to control HBV infection in this hyperendemic area.

Child↗
PubMed1996

A prospective study of transfusion-transmitted GB virus C infection: similar frequency but different clinical presentation compared with hepatitis C virus.

To study the incidence and outcome of GB virus C (GBV-C) infection in blood recipients. Serum samples collected in a prospective study were examined for GBV-C RNA by a nested polymerase chain reaction assay. Among the 400 adults who underwent cardiac surgery, 40 were positive for GBV-C RNA, including six whose pretransfusion sera were already positive and seven coinfected with hepatitis C virus (HCV) during transfusion. The risk of transmission was estimated to be approximately 0.46% per donor. GBV-C viremia was detectable 1 week after transfusion and could persist for 8 years. However, no evident symptoms or signs were noted in the 25 patients infected by GBV-C alone, and the average peak serum alanine aminotransferase activity was 31 IU/L only (range, 12 to 123), with persistently normal levels in 20 patients. In the seven patients coinfected with HCV, the clinical courses of posttransfusion hepatitis were similar to those infected by HCV alone. In eight patients with posttransfusion non-A approximately E hepatitis, only one was positive for GBV-C RNA. Sixty samples were chosen to test hepatitis G virus (HGV) sequences, 26 of the 30 GBV-C positives were positive for HGV RNA in contrast to none of the 30 GBV-C negative samples. In conclusion, GBV-C can be transmitted by transfusion in approximately 9% of patients who underwent cardiac surgery. Nevertheless, this virus does not seem to cause classic hepatitis in most instances.

Acute Disease↗
PubMed1996

N-linked glycosylation of hepatitis B surface antigens is involved but not essential in the assembly of hepatitis delta virus.

Hepatitis delta virus (HDV) is a defective virus requiring the hepatitis B virus (HBV) to provide hepatitis B surface antigens as the envelope protein. The hepatitis B surface antigens are posttranslationally modified by N-linked glycosylation, and its significance in HDV assembly was investigated with a cotransfection system using human hepatoma cell line Huh-7. After the N-linked glycosylation of HBsAg was blocked by tunicamycin treatment, the packaging of HDV in the culture system could be suppressed to a level as low as 5-10% of the untreated control. The extent of inhibition correlated with the increased concentrations of tunicamycin. In contrast, the loss of HBsAg glycosylation did not affect the efficiency of assembly of HBV particles. When the N-linked glycosylation site of small HBsAg at amino acid 146 was mutated from asparagine to glutamine, the mutant HBsAg packaged only a modest amount of HDV particles. The quantity and kinetics of formation of HDV particles in culture system were reduced by the depletion of HBsAg glycosylation. Therefore HDV, similar to influenza and vesicular stomatitis viruses, depends on glycosylation of the envelope proteins as a signal for envelope protein maturation and for virion formation.

Amino Acid Sequence↗
PubMed1996

Alcoholism, hepatitis B and C viral infections, and impaired liver function among Taiwanese aboriginal groups.

Viral hepatitis and alcoholism prevail in four major Taiwanese aboriginal groups. To study the relative importance of the acquisition of hepatitis B virus or hepatitis C virus infection and alcoholism to the presence of impaired liver function in these groups, the authors conducted a semistructured clinical interview for alcoholism and test for seromarkers for viral hepatitis among 993 cohort members enrolled in 1990-1992 in an ongoing prospective study (Taiwan Aboriginal Study Project). The subjects' blood specimens were tested for serum alanine aminotransferase/aspartate aminotransferase levels and for the presence of hepatitis B surface antigen and anti-hepatitis C virus antibody. The prevalence of a combination of an alanine aminotransferase level of > 35 IU/liter and an aspartate aminotransferase level of > 40 IU/liter, implying impaired liver function or advanced liver disease, was 4.3% overall. Univariate and multiple logistic regression analysis showed that, rather than chronic hepatitis B virus infection, hepatitis C virus infection and alcoholism were the two dominant risk factors that signalled the risk of liver damage among these Taiwanese aborigines. In addition, these two contributing factors were able to act synergistically to cause impaired liver function.

Alcoholism↗
PubMed1996

Chronic oral etoposide and tamoxifen in the treatment of far-advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a chemoresistant tumor that frequently expresses a high level of p 170 glycoprotein of the multidrug-resistance (MDR) gene. Preliminary data suggested that VP-16 showed modest activity in HCC. Recently, schedule-dependent cytotoxicity of VP-16 has been demonstrated. In this study, we tested the therapeutic efficacy of chronic oral VP-16 plus tamoxifen, a potential MDR-reversing agent, in patients with far-advanced HCC. METHODS: A prospective single-arm study was conducted in the National Taiwan University Hospital. To be eligible, patients must have had unresectable and non-embolizable HCC, objectively measurable tumors, adequate hemogram with absolute granulocyte count greater than or equal to 2,000/mm3, and platelet count greater than or equal to 1x10 (5)/mm3, total serum bilirubin less than or equal to 3.0 mg/dl, age less than or equal to 75 years, and a Karnofsky performance status of greater then or equal to 50%. The treatment included VP-16 (Bristol-Myers-Squibb, Princeton, NJ), 50 mg/m2/day, orally, Days 1 to 21, and tamoxifen (Pharmachemie B.V. Haarlem, Netherlands), 40 mg/day, orally, Days 1 to 21; repeated every 5 weeks. RESULTS: Between December 1990 and December 1993, a total of 33 patients were enrolled in the study. There were 28 men and 5 women, with a median age of 51 years. They received an average of 3.2 (range: 1-10) courses of chemotherapy. ECOG (Eastern Cooperative Oncology Group) Grade 3 and Grade 4 leucopenia developed in 6 patients (18.2%) and 4 (12.1%) patients, respectively. Grade 3 and 4 thrombocytopenia developed in 2 patients (6.1%). Treatment-related death occurred in one patient due to sepsis. Mild gastrointestinal toxicities were common with Grade 1 and 2 nausea. Grade 1 and 2 vomiting, Grade 1 and 2 diarrhea, and Grade 1 and 2 stomatitis, developed in 13 (39.4%), 7 (21.2%), 12 (36.4%), and 16 (48.5%) patients, respectively. Grade 3 and 4 gastrointestinal toxicities were rare. Deep vein thrombosis occurred in one patient (3.0%). Eight patients (24.2%, 95% confidence interval 11%-42%) had achieved a partial remission, with a median time-to-progression of 6 months (2-11). Median survivals of the responders and non-responders were 8.0 and 3.0 months, respectively (P < 0.05). The median Karnofsky performance status of the responders improved from 70% to 80%. CONCLUSIONS: Chronic oral VP-16 and tamoxifen has modest activity and acceptable toxicity in far-advanced HCC, and is a useful palliative treatment in about a quarter of such patients.

Administration, Oral↗
PubMed1996

Absence of extensive genetic heterogeneity of hepatitis C virus in antibody-negative chronic hepatitis C.

Hepatitis C virus (HCV) carriers usually have antibodies to HCV; however, there are viremic individuals without these antibodies. To investigate whether variations of the viral genome are responsible for this discrepancy, the nucleotide and deduced amino acid sequences of HCV capsid and nonstructural regions obtained from 15 viremic patients were examined. These 15 patients were infected with type 1b HCV, and 10 did not have antibody to HCV assayed with second-generation tests. The nucleotide homology of the 5 seropositive and 10 seronegative patients with the HCV prototype sequence were 91.6% and 91.9%, respectively, in the capsid region. There was no apparent difference in the deduced amino acid sequences between the two groups of patients studied (94% vs. 95%). The nucleotide and amino acid sequences of a part of the nonstructural region 3 also showed similar results. These findings suggest that absence of antibodies against both capsid and nonstructural peptides in HCV carriers is not caused by genetic heterogeneity of the viral epitopes.

Adult↗
PubMed1996

Superinfection by homotypic virus in hepatitis C virus carriers: studies on patients with post-transfusion hepatitis.

Although heterotypic superinfection and mixed infections of hepatitis C virus (HCV) may be possible for hepatitis flares in chronic hepatitis C, the possibility of homotypic HCV superinfection in HCV carriers with post-transfusion hepatitis has not been explored. Six HCV carriers with post-transfusion non-A, non-B hepatitis found in a prospective study of post-transfusion hepatitis were included. Serum samples before transfusion and during hepatitis were selected to determine genotypes of HCV and nucleotide sequences of the hypervariable region (HVR). The genotypes identified before and after transfusion were concordant in all. There were four with type 1b and one each with type 2a and type 2b. Amplified nucleotide sequences of the HVR before transfusion and during hepatitis were compared in four patients, and a > 95% homology was observed in three, suggesting persistence of original viruses. In contrast, only a 51% homogeneity was seen in a given patient, suggesting a homotypic HCV superinfection. Phylogenetic tree analysis validated further these findings. This study implies that HCV carriers can be reinfected by homotypic HCV, and this may contribute to hepatitis flares in chronic hepatitis C. These findings also confirm a weak or inadequate protective immunity in HCV infection and justify protection from reinfection of HCV of patients with chronic hepatitis C.

Adult↗
PubMed1996

A program for eradication of hepatitis B from Taiwan by a 10-year, four-dose vaccination program.

Approximately 15 percent of the Taiwanese population are chronic carriers of hepatitis B virus (HBV), among the highest rates in Asia. In July 1984, the Taiwanese government initiated a nationwide HBV-vaccination program. The program began with educational efforts and voluntary prenatal screening for HBsAg. Infants of HBsAg-carrier mothers received a four-dose regimen of hepatitis B vaccine. Those born to highly infectious mothers also received a dose of hepatitis-B immune globulin within 24 hours after birth. Seroepidemiologic studies were conducted using a random sample of infants. Serum samples were collected at 18, 24, 36, and 48 months and analyzed via radioimmunoassay for HBsAg, anti-HBs, and anti-HBc. Infants of highly infectious mothers had HBsAg positivity rates of 14.2 percent (vaccine plus HBIG) and 19.7 percent (vaccine only) when on schedule, and 17.0 percent when off schedule. Infants of moderately infectious mothers had an HBsAg positivity rate of 3.0 percent when on schedule and 6.4 percent when off schedule. These low positivity rates persisted throughout the 48-month follow-up period. This represents a dramatic improvement upon the 40 to 96 percent vertical transmission rate seen before the program implementation. This program demonstrates that mass immunoprophylaxis for HBV is feasible, and provides practical strategies for other Asian countries.

Adolescent↗