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Biomedical subjects

D S Chen

Publications and source records attributed to D S Chen.

At least 127 records · Page 7Linked to original sources
PubMed1996

Chronic hepatitis C without anti-hepatitis C antibodies by second-generation assay. A clinicopathologic study and demonstration of the usefulness of a third-generation assay.

To study the clinicopathologic features of hepatitis C viremic patients negative for hepatitis C antibodies (anti-HCV) by current second-generation assay, we categorized 139 consecutive histologically verified patients with chronic non-A, non-B hepatitis into three groups: 121 (87%) were positive for second-generation anti-HCV (group A); 10 (7%) were negative for second-generation anti-HCV but positive for HCV RNA (group B); and 8 (6%) were negative for both antibodies and viremia (group C). Six (60%) of group B patients could be, further detected by a new third-generation assay, but none of group C patients was third-generation anti-HCV-positive. The demographic features, mean peak serum alanine aminotransferase levels, HCV genotype distribution, and histologic changes were comparable among the three groups. The study indicates that most patients with chronic hepatitis C in Taiwan could be identified by current second-generation assay, and viremic but antibody seronegative patients were clinicopathologically similar to the seropositives. Most patients of the latter group could be diagnosed by a third-generation assay, indicating the usefulness of this assay.

Chronic Disease↗
PubMed1996

Serotyping of hepatitis C virus in chronic type C hepatitis in Taiwan: correlation with genotypes.

To evaluate the usefulness of a new serologic assay to group hepatitis C virus (HCV), genotypes identified by this serotyping method were compared to those identified by a polymerase chain reaction (PCR) assay with type-specific primers in 71 Taiwanese patients with chronic type C hepatitis. The group-specific antibodies against different HCV genotypes were detected by using an enzyme-linked immunosorbent assay (ELISA) based on group-specific recombinant peptides (C14-1 and C14-2) within the NS4 region. Among 71 patients positive for current second-generation HCV antibodies, HCV RNA was detected in 55 patients by PCR with primers from the 5' untranslating region, and in 52 by genotype-specific PCR. In 49 (89%) of 55 viremic patients, the results of serotyping by ELISA showed complete agreement with those determined by PCR genotyping, and none of the patients showed a group opposite to that of HCV genotype. The positive rate of group-specific antibodies (69/71;97%) was even better than that of the PCR (55/71;78%). We conclude that this new serotyping assay is highly sensitive and specific for the determination of HCV genotypes, and will be useful in future epidemiologic studies, as well for clinical application.

Adult↗
PubMed1996

Least microtransfusion from mother to fetus in elective cesarean delivery.

OBJECTIVE: To examine the variability of maternal-fetal microtransfusion in different modes of delivery, as measured by hepatitis B surface antigen (HBsAg) and placental alkaline phosphatase. METHODS: We recruited 97 HBsAg-positive pregnant women. The mode of delivery included elective cesarean in 16, normal spontaneous vaginal delivery in 56, vacuum or forceps delivery in 12, and emergency cesarean after labor in 13. We measured HBsAg and placental alkaline phosphatase levels in 97 pairs of maternal and fetal blood samples collected at delivery. RESULTS: The mean maternal placental alkaline phosphatase levels did not differ among these four groups. The mean cord placental alkaline phosphatase level of the elective cesarean group was the lowest (P < .05). All samples of cord sera for this group were negative for HBsAg, compared with 38 of 56, eight of 12, and seven of 13 in the spontaneous vaginal, vacuum or forceps, and emergency cesarean groups, respectively (P < .05). CONCLUSION: The level of mother-to-fetus microtransfusion least in the elective cesarean group, as revealed by both the lowest cord placental alkaline phosphatase and HBsAg levels. These observations may have implications for reducing perinatal transmission of blood-borne viruses.

Alkaline Phosphatase↗
PubMed1996

Chromosome 1p aberrations are frequent in human primary hepatocellular carcinoma.

To investigate the chromosomal changes in hepatocellular carcinoma in humans, metaphase chromosomes obtained directly from short-term culture of resected human primary hepatocellular carcinoma tissues were studied in seven patients. Among the five successfully karyotyped cases, cytogenetic analysis showed highly different and complex chromosomal changes in the cancer tissue in four patients. Structural aberrations of chromosome 1 and deletion of 1p with breakpoints at p22 or p32 were the most common abnormalities, and were found in the four successfully analyzed cases. Loss of 1p may be important in hepatocarcinogenesis, and warrants further characterization by molecular genetic analysis.

Adult↗
PubMed1996

Surgical resection for recurrent hepatocellular carcinoma: prognosis and analysis of risk factors.

BACKGROUND: Hepatocellular carcinoma (HCC) is common in Asian countries, and tumor recurrence is the most common cause of treatment failure after curative resection. Repeated hepatectomy is performed only for selected patients because most patients with HCC also have liver cirrhosis and poor liver function reserve. The purposes of this study were to clarify the outcome of the patients after second hepatectomy for recurrent HCC and to evaluate the prognostic factors after second hepatectomy. METHODS: We used retrospective cohort study to examine the disease-free survival, cumulative survival, and possible prognostic factors for recurrence and death in 59 patients who underwent surgical resection for recurrent HCC at the National Taiwan University Hospital from August 1986 to December 1993. Another 64 patients with unresectable recurrent HCC were used as a historical control group. The survival curves between those patients with resectable HCC and those with unresectable HCC were compared. RESULTS: After resection for recurrent HCC, gender and multiplicity (n > 3) of tumor affect recurrence rate (p = 0.046 and 0.021, respectively), whereas gender, age, and tumor invasiveness affect survival rate significantly (p = 0.024, 0.021, and 0.046, respectively). The survival rate of patients with resectable HCC was significantly better than that of those with unresectable HCC. CONCLUSIONS: For recurrent HCC surgical resection is an effective mode of treatment in selected patients. Whether surgery is better than other modes of treatment in the treatment of resectable recurrent HCC demands further investigation.

Adult↗
PubMed1996

Ultrasound-guided cutting biopsy for the diagnosis of hepatocellular carcinoma--a study based on 420 patients.

BACKGROUND/AIMS: To evaluate ultrasound-guided cutting biopsy for hepatocellular carcinoma, we report findings from 10 years of experience. METHODS: We performed 455 ultrasound-guided cutting biopsies of hepatic tumors in 420 patients with hepatocellular carcinoma from 1981 to 1990. RESULTS: Liver tissues were adequately sampled for a histological diagnosis of hepatocellular carcinoma in the initial biopsy in 391 sessions. The remaining 64 were proved to have hepatocellular carcinoma after subsequent studies. Ultrasound-guided biopsy changed the initial diagnosis in 9 of the 420 patients: three had been diagnosed with liver abscess, and six with metastatic liver tumors. Complications of the biopsy were rare: the tumor had spread to the chest wall in nine, and internal bleeding was noted in five patients. There was no mortality and no other sequelae. CONCLUSIONS: Ultrasound-guided biopsy of hepatic tumors is important in the diagnosis of liver cancer, but this technique should be applied only when the image diagnosis and results of fine needle biopsy are equivocal to minimize possible complications. For patients with small HCCs, who are candidates for surgical resection of hepatocellular carcinoma or liver transplantation, it should not be considered as a first-step invasive procedure.

Adolescent↗
PubMed1996

Elucidation of Islamic drugs in Hui Hui Yao Fang: a linguistic and pharmaceutical approach.

Hui Hui Yao Fang, an Islamic formulary, was probably the official formulary of the Mongolian administration during the Yuan dynasty (13th-14th century) in China. In the three chapters of prescriptions that remain extant today, there are 517 Islamic drugs carrying Arabic or Persian names, each with its Chinese transliteration. Chapter 12 deals with the 'wind' diseases, containing 199 Islamic drugs. In this research, 129 items were identified, and each of which was assigned to a definite taxon; these are the most frequently cited drugs in the formulary. Identifications were corroborated by botanical, pharmacological and phonetic considerations. This exercise demonstrates the inherent affinity between Islamic and Chinese medicines. The reciprocal influence between them greatly enriched the content of these two important bodies of drug science, thus, setting a pattern for the synthesis of drug knowledge and the regulation of therapeutic substances. Recognition of different bodies of ethnomedicine is necessary in view of the fact that there is an increasing mobility of people today, who tend to bring with them their drug knowledge.

Formularies as Topic↗
PubMed1996

Analysis of rearranged T cell receptor (TCR) V beta transcripts in livers of primary biliary cirrhosis: preferential V beta usage suggests antigen-driven selection.

The presence of autoantibodies to mitochondrial pyruvate dehydrogenase complex-E2 (PDC-E2) and self-reactive T cells to PDC suggests that autoimmune mechanisms may be involved in the pathogenesis of primary biliary cirrhosis (PBC). Molecular analysis of intrahepatic TCR repertoire may provide valuable information on a T cell mechanism for PBC immunopathogenesis. We therefore analysed the TCR V beta usage in different regions of the livers removed during transplantation from two PBC patients. Using reverse transcription and polymerase chain reaction (RT-PCR), a limited heterogeneity of rearranged TCR V beta transcripts was demonstrated in different locations of the same liver. Sequence analysis of V beta-D beta-J beta (CDR3: the third complementarity determining region) showed the presence of conserved residues, no random N additions, and a common motif within CDR3. These results suggest that T cells homing to PBC liver may be antigen-driven. To elucidate further whether an immune deviation related to T helper 1 cell (Th1) or Th2 responses may exist in PBC, intrahepatic mRNA expression of IL-2, IL-4 and interferon-gamma (IFN-gamma) was examined by the RT-PCR method. IL-2 and IFN-gamma could be amplified, whereas IL-4 was virtually undetectable in the livers from the two patients with PBC. The findings suggest that polarization of intrahepatic lymphokine expression toward the Th1-dominant pattern may be significant in the immunopathogenesis of PBC.

Amino Acid Sequence↗
PubMed1996

Allelic loss on chromosomes 4q and 16q in hepatocellular carcinoma: association with elevated alpha-fetoprotein production.

BACKGROUND & AIMS: In human hepatocellular carcinoma, restriction fragment length polymorphism analysis has shown frequent allelic loss on chromosomes 4q and 16q. To better define the commonly affected region for further positional cloning of the putative tumor-suppressor genes contained in these two chromosome arms, microsatellite polymorphism analysis was conducted to analyze extensively the allelic loss on both chromosome loci. METHODS: DNA from 42 pairs of large hepatocellular carcinoma (> 5 cm) and corresponding nonneoplastic liver tissues were prepared. Allelic loss on chromosome 4q and 16q was investigated by 13 or 12 sets of microsatellite polymorphic markers. RESULTS: The frequency of allelic loss on chromosome 16q was 70%, and the common region was mapped to 16q22-23. An even higher frequency (77%) was found on chromosome 4q with the common region mapped to 4q12-23. The allelic loss of chromosome 4q was significantly associated with hepatocellular carcinoma of elevated serum alpha-fetoprotein but not with those of normal level (91% vs. 30%; Fisher's Exact Test, two-tailed P = 1.12 x 10(-4)). CONCLUSIONS: The results form the basis for further positional cloning of putative tumor-suppressor genes on chromosome 4q and 16q. Moreover, the one on chromosome 4q might shed light on the mechanism of alpha-fetoprotein expression in hepatocellular carcinoma.

Alleles↗
PubMed1996

Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C.

BACKGROUND & AIMS: Sustained response to interferon treatment for chronic hepatitis C is unsatisfactory. This study examined whether combining interferon alfa with ribavirin induces a better sustained efficacy than interferon alone in the treatment of chronic hepatitis C. METHODS: Sixty noncirrhotic patients with chronic hepatitis C were randomly assigned to three groups. Group 1 received 1200 mg oral ribavirin daily plus 3 million units of recombinant interferon alfa 2a thrice weekly for 24 weeks, group 2 received the same dose of interferon alfa 2a alone for 24 weeks, and group 3 received no treatment. The patients were then followed up for an additional 96 weeks. RESULTS: At the end of treatment, a complete response (normal serum alanine aminotransferase level and undetectable serum hepatitis C virus RNA) was achieved in 16 of the 21 patients in group 1 (76%), as compared with 6 of 19 in group 2 (32%) and none in group 3. At 96 weeks after the end of treatment, patients in group 1 sustained a higher complete response rate than patients in group 2 (43% vs. 6%). CONCLUSIONS: Combined treatment with ribavirin and interferon alfa 2a for 24 weeks is more effective than interferon alfa 2a alone for the treatment of chronic hepatitis C. The biochemical and virological responses were sustained in about one half of the treated patients for at least 2 years after cessation of the therapy.

Adult↗
PubMed1996

Identification of humoral antigenic determinants in the hepatitis C virus NS3 protein.

Immunoblot analysis on serum samples from 90 patients with chronic hepatitis C virus infection revealed four putative immunogenic regions within the NS3 protein of the virus: E (around aa 1250/ 1251), A (within aa 1250-1334), A/B (around aa 1323 and 1334), and B/C (around aa 1407 and 1412). Among them, region E was most immunodominant, and region A was recognized much less frequently by patients with cirrhosis than by those with chronic hepatitis (10% vs. 46%, chi 2 = 12.05, P < .01). The results suggest that region A might be a potential prognostic marker to differentiate chronic hepatitis from cirrhosis.

Chronic Disease↗
PubMed1996

Phylogenetic analysis of GB virus C: comparison of isolates from Africa, North America, and Taiwan.

A group of flavi-like GB viruses (GBV-A, -B, and -C) has been discovered and partially characterized. Only GBV-C is found in humans. Nucleotide sequences of the putative helicase gene of the GBV-C genome were determined in 21 Taiwanese patients and compared with isolates from Africa and North America by phylogenetic analysis. The average similarities of Taiwanese isolates to those from West Africa, East Africa, Canada, and United States were 83%, 85%, 78%, and 82%, respectively. Phylogenetic analysis of the NS3 region showed that 81% of the Taiwanese isolates were more closely related to the East African isolate. GBV-C isolates from Taiwan could be classified into at least 3 groups. These data suggest that GBV-C isolates cloned from different geographic areas have genetic heterogeneity.

Africa↗
PubMed1996

Serum hepatitis C virus titers in the progression of type C chronic liver disease. With special emphasis on patients with type 1b infection.

The correlation of serum hepatitis C virus (HCV) titers to the progression of type C chronic liver disease remains controversial. We have investigated the relationship between serum HCV titers and different histological stages of chronic liver disease, including chronic persistent hepatitis (CPH), chronic active hepatitis and/or liver cirrhosis (CAH/LC), and hepatocellular carcinoma (HCC) in 94 well-characterized Taiwanese patients. The mean age of patients in the HCC group was significantly older than those in the CPH and CAH/LC groups, whereas those in the CAH/LC group had the highest mean serum alanine aminotransferase level among the three groups. The prevalence of HCV type 1b increased with the progression of histological severity, and the mean serum titer of the HCC group was significantly higher than that of CPH group. The difference of virus titers between the HCC group and those of the other two groups became more significant when only type 1b virus-infected patients were analyzed. In conclusion, elevated serum HCV titers are more frequently observed among Taiwanese patients with advanced type C chronic liver disease, an association not related to the high prevalence of HCV type 1b infection in such patients.

Adult↗
PubMed1996

Rapid hepatic failure associated with a contracted liver mimicking cirrhosis in a case of nasopharyngeal carcinoma with liver metastasis.

A 46-year-old women had an undifferentiated nonkeratinizing nasopharyngeal carcinoma, locally controlled by radiotherapy. Initially, she had normal liver function tests and normal hepatic ultrasonography. Seven months later, she experienced a rapidly progressive hepatic failure manifested by the development of ascites, elevation of serum bilirubin level, and prolongation of prothrombin time. Imaging studies showed a contracted liver and serum biochemical tests were compatible with chronic liver disease, except for an increase of alkaline phosphatase and gamma-glutamyl transpeptidase levels. An endoscopic retrograde cholangiogram ws compatible with changes of sclerosing cholangitis. The patient died of hepatic decompensation within two months. A liver necropsy disclosed diffuse infiltration of carcinoma cells into the hepatic sinusoids and obliterative angio-invasion of the tumor cells with massive fibrotic stroma replacing almost all hepatocytes. In situ hybridization demonstrated expression of Epstein-Barr virus transcripts EBER1 in the tumor cells and proved a metastatic nasopharyngeal carcinoma. The contracted liver is likely to be explained by the tumor-associated desmoplastic change and the obliterative angio-invasion of the tumor. It is important to be aware that, although rare, such an unusual pattern of liver metastasis may mimick cirrhosis clinically and cause rapid hepatic failure in patients with nasopharyngeal carcinoma.

DNA Probes↗
PubMed1996

The helicase activity associated with hepatitis C virus nonstructural protein 3 (NS3).

To assess the RNA helicase activity of hepatitis C virus (HCV) nonstructural protein 3 (NS3), a polypeptide encompassing amino acids 1175 to 1657, which cover only the putative helicase domain, was expressed in Escherichia coli by a pET expression vector. The protein was purified to near homogeneity and assayed for RNA helicase activity in vitro with double-stranded RNA substrates prepared from a multiple cloning sequence and an HCV 5' nontranslated region (5'-NTR) or 3'-NTR. The enzyme acted successfully on substrates containing both 5' and 3' single-stranded regions (standard) or on substrates containing only the 3' single-stranded regions (3'/3') but failed to act on substrates containing only the 5' single-stranded regions (5'/5') or on substrates lacking the single-stranded regions (blunt). These results thus suggest 3' to 5' directionality for HCV RNA helicase activity. However, a 5'/5' substrate derived from the HCV 5'-NTR was also partially unwound by the enzyme, possibly because of unique properties inherent in the 5' single-stranded regions. Gel mobility shift analyses demonstrated that the HCV NS3 helicase could bind to either 5'- or 3'-tailed substrates but not to substrates lacking a single-stranded region, indicating that the polarity of the RNA strand to which the helicase bound was a more important enzymatic activity determinant. In addition to double-stranded RNA substrates, HCV NS3 helicase activity could displace both RNA and DNA oligonucleotides on a DNA template, suggesting that HCV NS3 too was disposed to DNA helicase activity. This study also demonstrated that RNA helicase activity was dramatically inhibited by the single-stranded polynucleotides. Taken altogether, our results indicate that the HCV NS3 helicase is unique among the RNA helicases characterized so far.

Animals↗
PubMed1996

Hepatitis C viral infection in thalassemic children: clinical and molecular studies.

To determine and correlate the liver function profile, hepatitis C virus (HCV) genome, anti-HCV, genotypes, quantitation, and nucleotide sequence variability in polytransfused thalassemic children, 61 such children were studied prospectively for 4 y. Twenty-six had HCV infection. The average age, number of transfusions, and alanine aminotransferase (ALT) levels of the HCV-infected group were higher than those of the 35 children without HCV infection. None was infected after the initiation of anti-HCV screening in donor blood. Liver biopsies were performed in six HCV-infected and eight HCV-noninfected thalassemic children, and portal fibrosis was found more frequently in the HCV-infected group. Quantitation of HCV RNA was done by the competitive polymerase chain reaction method, and the titer was about 1 x 10(6) to 5 x 10(8) copies/mL. The titer did not change significantly over the 4-y follow-up period and did not correlate with ALT levels. Nineteen HCV-infected patients were genotyped; 15 were Okamoto/Simmonds type II/1b, two were type III/2a, and two were type IV/2b. The hypervariable region of the HCV genome (E2/NS1) was cloned and sequenced in two serum samples from one patient collected at a 2-y interval, as the ALT levels decreased. The variation rate was estimated to be 1.2-1.7 x 10(-2)/nucleotide/y. The results showed that, in polytransfused thalassemic children, 43% (26/61) contracted HCV. We conclude that HCV infection may cause elevated ALT levels and portal fibrosis of the liver, whereas the viral titer and genotypes do not parallel ALT levels.

Adolescent↗