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Biomedical subjects

D S Chen

Publications and source records attributed to D S Chen.

At least 73 records · Page 4Linked to original sources
PubMed1998

Involvement of the 5' proximal coding sequences of hepatitis C virus with internal initiation of viral translation.

The 5' nontranslated region (NTR) of hepatitis C virus (HCV) consists of 341 nucleotides (nt). This region comprises the majority of the internal ribosome entry site (IRES) which controls the efficiency of viral translation. Previous studies of the 3' boundary of the HCV IRES yielded conflicting data regarding the involvement of viral coding sequences in IRES activity. We therefore studied the functional significance of the 5' proximal coding sequences of the HCV core gene on IRES activity. We constructed monocistronic and bicistronic DNAs that contained either a chloramphenicol acetyl transferase (CAT) gene or a luciferase (Luc) gene as the reporter. Results from both in vitro and in vivo experiments indicated that the optimal IRES ranged within nt 1-371. Further mutational analyses of sequences surrounding the initiation codon revealed that primary sequences downstream of the AUG initiator rather than the secondary structure are important in regulating optimal IRES function. We are also able to demonstrate that a non-AUG codon could be used to initiate the synthesis of a reporter protein, albeit with lower efficiency. These findings bear important implications for the HCV IRES secondary structures.

5' Untranslated Regions↗
PubMed1998

Inhibition of the membrane translocation and activation of protein kinase C, and potentiation of doxorubicin-induced apoptosis of hepatocellular carcinoma cells by tamoxifen.

Hepatocellular carcinoma (HCC) is characterized by high drug resistance to currently available chemotherapeutic agents. In a prospective clinical study, we have demonstrated that high-dose tamoxifen significantly enhanced the therapeutic efficacy of doxorubicin in patients with far-advanced HCC. In a search for a possible mechanism, we found that tamoxifen at a clinically achievable concentration (2.5 microM) significantly enhanced doxorubicin-induced cytotoxicity and apoptosis of Hep-3B cells, a multidrug resistance (MDR)-1 expressing HCC cell line. This synergistic cytotoxic effect of tamoxifen, at this concentration, however, was not mediated by MDR inhibition. Instead, as evidenced by both western blot and immunofluorescence studies, tamoxifen inhibited the cytoplasmic-membrane translocation of protein kinase C (PKC)-alpha. 12-O-Tetradecanoylphorbol-13-acetate (TPA) restored the membrane translocation of PKC-alpha and abrogated the synergistic cytotoxicity of tamoxifen. We also showed that tamoxifen, at this concentration, did not directly affect the enzyme activity of PKC. Further, membrane translocation of other membrane-bound proteins, such as Ras protein, was similarly inhibited by tamoxifen, but could not be restored by the addition of TPA. Together, these data suggested that tamoxifen may act on the cytoplasmic membrane, and thereby inhibit PKC-alpha translocation to the membrane where it is activated. We hypothesize that high-dose tamoxifen may be an effective modulator of doxorubicin in the treatment of HCC, and suggest that biochemical modulation of PKC as a measure to improve systemic chemotherapy for HCC deserves further investigation.

Animals↗
PubMed1998

Somatosensory evoked potentials in subclinical portosystemic encephalopathy: a comparison with psychometric tests.

We prospectively studied the role of somatosensory evoked potentials (SEPs) and psychometric tests in the assessment of subclinical portosystemic encephalopathy (PSE) in 61 cirrhotic patients with grade 0 PSE and 20 controls. Six additional uneducated controls underwent only psychometric tests. Median nerve-evoked cortical responses were recorded for N20-N65 interpeak latencies (IPLs). Psychometric tests were conducted within 4 hours of SEP testing. Seven (26.9%) controls and 30 (49.2%) cirrhotic patients had abnormal psychometric test results (writing sample tests, 20; five-point star tests, 17; number-connection tests, 19; and following-a-track tests, 18); seven controls and 25 cirrhotic patients had 6 or fewer years of education; 7 controls and 28 cirrhotics were older than 50 years of age. Cirrhotic patients (47.6 +/- 8.3 milliseconds) had higher N20-N65 IPLs than controls (40.2 +/- 3.0 milliseconds; P < .001). Twenty-nine (47.5%) cirrhotic patients had abnormal N20-N65 IPLs. Of the 26 cirrhotic patients with more than 6 years of education, 15 (57.7%) had abnormal N20-N65 IPLs and 5 (19.2%) had abnormal psychometric test results (P = .005). Our data show that N20-N65 IPLs of SEPs are helpful in the assessment of subclinical PSE; 47.5% of cirrhotic patients had subclinical PSE. Poorly educated and older subjects tended to have abnormal psychometric test results. SEPs were not affected by education and age and were more sensitive than psychometric tests in the assessment of subclinical PSE in better-educated cirrhotic patients.

Adult↗
PubMed1998

Hepatocyte growth factor stimulates the growth and activates mitogen-activated protein kinase in human hepatoma cells.

Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and various epithelial cells. Unexpectedly, it has been reported to inhibit the growth of hepatoma cells in vitro. To clarify this phenomenon, we examined the effects of recombinant baculovirus-expressed HGF on the growth of 6 human hepatoma cell lines. The growth of Hep3B and HepG2 cells was markedly stimulated to 1.8- and 1.7-fold, respectively, PLC/PRF/5 to 1.4-fold, and SK-Hep-1 to 1.2-fold in a dose-dependent manner under HGF concentrations below 20 ng/ml. Neither HuH-7 nor HCC36 were affected. None of these cells were inhibited. All these cells expressed c-Met, the membrane receptor for HGF, and their c-Met would be activated to be phosphorylated upon addition of HGF. They also contained the ERK2 subgroup of mitogen-activated protein kinases (MAPKs). When HGF was added, their ERK2 would also be phosphorylated. The extent of ERK2 phosphorylation was partially correlated to their growth response to HGF. In conclusion, HGF could stimulate the growth of certain human hepatoma cells, probably through activation of c-Met and MAPKs.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Icteric type hepatocellular carcinoma: revisited 20 years later.

Icteric type hepatocellular carcinoma is rare, and a poor prognosis has been demonstrated in the past. We performed this study to re-evaluate prognosis since the availability of modern diagnostic modalities. Of 3921 patients with hepatocellular carcinoma in our hospital, 9 patients who presented with tumor fragments in common bile duct and had a patent portal vein were submitted for analysis. Cholangiocarcinoma was suspected in 7 patients before the study was completed, and icteric type hepatocellular carcinoma was diagnosed in all 9 patients after serial studies that included serum alpha-fetoprotein levels, computed tomography, angiography, and histology. The prognosis was better in the 4 resectable patients (survival time 16, 31, 33, and 63 months, respectively), and was extremely poor for the 5 patients who received palliative treatment only (mean survival time, 4.5 months). Because of the apparently discrepant outcomes, this specific type of hepatocellular carcinoma should be kept in mind in areas where hepatocellular carcinomas are prevalent, and the suspected cases should be thoroughly investigated, because prognosis may be improved when resection is done at an earlier stage.

Aged↗
PubMed1998

Effects of GB virus-C/hepatitis G virus on hepatitis B and C viremia in multiple hepatitis virus infections.

We found that patients with dual HBV and GBV-C/HGV infection had comparable serum HBV DNA positivity and mean virus concentration compared with age-matched HBV carriers, and those with triple infection had a significantly lower HBV DNA positivity. Serum HCV RNA positivity and mean virus titer were similar between HCV carriers with or without GBV-C/HGV co-infection, and those with GBV-C/HGV co-infection seemed to have a lower serum ALT level. These data suggest that GBV-C/HGV infection exerts no significant suppression on levels of chronic hepatitis B or hepatitis C viremia.

Adult↗
PubMed1998

Antibodies to E2 protein of hepatitis G virus in children: different responses according to age at infection.

OBJECTIVES: To study viral persistence and antibody responses after hepatitis G virus (HGV) infection in children of various ages. STUDY DESIGN: We performed an enzyme immunoassay for antibodies to E2 protein (anti-E2) of HGV and reverse-transcription polymerase chain reaction assay for HGV RNA on serum samples. RESULTS: Of 28 infants born to HGV RNA-positive mothers, 17 were found to be positive for HGV RNA. None were positive for anti-E2. All 17 infected infants continued to have viremia except 1 who converted to HGV RNA-negative status at 24 months. Six infants had mild elevations of alanine aminotransferase levels (5 HGV-positive and 1 HGV-negative). An additional 14 HGV-infected children (aged 6 months to 14 years) with posttransfusion HGV infection were tested for anti-E2 3 months and 12 months after blood transfusion. None of the HGV RNA-positive serum samples were positive for anti-E2; however, 4 of the 8 children with resolving HGV infection were positive for anti-E2 1 year later. CONCLUSIONS: Mother-to-infant transmission of HGV resulted in a high viral persistence rate and lack of immune responses to HGV. In contrast, anti-E2 appeared in children who recovered from posttransfusion HGV infection. Mode of transmission and age at infection may be important factors in determining persistent HGV infection and defective immune response to HGV.

Adenovirus E2 Proteins↗
PubMed1998

Precore stop codon mutant in chronic hepatitis B virus infection in children: its relation to hepatitis B e seroconversion and maternal hepatitis B surface antigen.

BACKGROUND/AIMS: The aims of this study were to investigate the significance of the precore stop codon mutant in the natural course of hepatitis B virus infection in children, and the influence of maternal transmission. METHODS: Sequential sera from 80 hepatitis B virus carrier children both before and after e seroconversion during long-term follow-up were studied using the polymerase chain reaction-amplification created restriction site method. Direct sequencing of the precore region was performed in 89 sera from 32 of the 80 children. RESULTS: The precore stop codon mutant coexisting with wild strain was found in 10% of children initially, and later in 25% of children before e seroconversion. After e seroconversion, wild type was still present in 75% and mutant in 39% of children at the end of follow-up. The mutant alone was present in 15% of anti-HBe positive children without concomitant aminotransferase elevation. Children with earlier emergence of this mutant tended to have higher peak aminotransferase levels. This mutant emerged less frequently in children of hepatitis B virus carrier mothers (37.5%) than in those of non-carrier mothers (65%) (p<0.05). CONCLUSIONS: These observations suggest that this mutant is selected by host immune pressure, but is not an initiator in the loss of immune tolerance during childhood chronic hepatitis B virus infection.

Adolescent↗
PubMed1998

Infrequent mutations and no methylation of CDKN2A (P16/MTS1) and CDKN2B (p15/MTS2) in hepatocellular carcinoma in Taiwan.

CDKN2A (p16INK4A/MTS1) and CDKN2B (p15INK4B/MTS2) have recently been shown to be potent inhibitors of the cyclin D/cyclin-dependent kinase-4 complex. Both genes are candidates for the putative tumour suppressor genes located at chromosome 9p21 and are frequently inactivated in many human cancers through homozygous deletion. More recently, another reported pathway of inactivation involves loss of transcription associated with de novo methylation of the 5' CpG island of p16/MTS1 and p15/MTS2 in human cancers. We examined a total of 34 tumours from 30 hepatocellular carcinoma (HCC) patients for deletion, mutation and DNA methylation of these two genes by polymerase chain reaction (PCR) amplification, sequence analysis and Southern blot. Homozygous deletions of P16/MTS1 exon 1 were only identified in 1 of 30 cases (3%). Homozygous deletions of p15 exon 1 or exon 2 were found in 7 of 30 cases (13%). Automated sequencing analysis of p16 exon 1 and 2 and p15 exon 1 and 2 failed to demonstrate mutations in either p16 or p15 in any of these specimens. No aberrant 5' CpG island hypermethylation of p16 or p15 was found in any of the primary tumours by Southern blot. These data suggest that the p16/MTS1 gene has a limited role in HCC. However, deletions of the p15/MTS2 gene are found in 13% HCC and might be involved in a subset of HCC.

Adult↗
PubMed1998

Telomerase activity and telomere length in human hepatocellular carcinoma.

Telomerase activity is activated and telomere length altered in various types of cancers, including hepatocellular carcinoma (HCC). A total of 39 HCC tissues and the corresponding non-tumour livers were analysed and correlated with clinical parameters. Telomere length was determined by terminal restriction fragment assay, and telomerase activity was assayed by telomeric repeat amplification protocol. Telomerase activity was positive in 24 of the 39 tumour tissues (1.15-285.13 total product generated (TPG) units) and in six of the 39 non-tumour liver tissues (1.05-1.73 TPG units). In the 28 cases analysed for telomere length, telomere length was shortened in 11 cases, lengthened in six cases, and unaltered in 11 cases compared with non-tumour tissues. Neither telomere length nor telomerase activity was correlated to any clinical parameters.

Adult↗
PubMed1998

Prevalence and infectivity of hepatitis G virus and its strain variant, the GB agent, in volunteer blood donors in Taiwan.

BACKGROUND: The prevalence of hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C) is high in non-virus-inactivated plasma products, but, persistent infection in recipients is relatively low. STUDY DESIGN AND METHODS: Stored samples from transfusion donors and recipients in a prospective study of posttransfusion hepatitis were tested for HGV RNA and antibody to the E2 protein (anti-E2). RESULTS: Thirty-two (2.1%) of the 1500 qualified donors were positive for HGV RNA. Twenty-four persons had received a transfusion of blood from one of these 32 viremic donors. Of these 24 recipients, 3 were positive for HGV RNA before transfusion. Of the remaining 21 recipients, 8 became viremic after transfusion, while the other 13 were not infected. Four of the eight infected recipients were persistently positive for HGV RNA, while four became negative in 1 to 3 years. Three of the four patients with HGV clearance seroconverted to anti-E2 positivity. Comparison of the viral titer, viral sequences at E2, storage period of blood donations, and clinical data in the infected and noninfected recipients revealed no significant differences. However, the noninfected recipients seemed to have a higher prevalence of anti-E2 before transfusion. CONCLUSION: The prevalence of HGV viremia in volunteer blood donors in Taiwan is 2.1 percent, and blood from 0.6 percent of them actually causes HGV infection in the recipients. In half of infected recipients, clearance of HGV occurs. Anti-E2 appears in most recipients whose viremia is cleared.

Adult↗
PubMed1998

Long-term functional results of contralateral C7 transfer.

From 1986 to 1994, 82 patients with brachial plexus root avulsion were operated on using a contralateral C7 nerve-root transfer. Forty-four patients underwent a one-stage procedure in which the distal end of the ulnar nerve was anastomosed to the contralateral C7 root, and the other 38 underwent a two-stage procedure (first phase: C7 root --> ulnar nerve; second phase: ulnar nerve --> recipient nerve). Twenty postoperative cases were followed-up for 2 years. Of them, the ulnar nerve was transferred to the musculocutaneous nerve in six cases, with recovery of the biceps up to M3 in four and S3 in five cases; the ulnar nerve was transferred to the median nerve in eight cases, with recovery of the wrist and finger flexors up to M3 in five and S3 in six cases; the ulnar nerve was transferred to the radial nerve in four cases, with recovery of the triceps up to M4 in two and S3 in three cases; and the ulnar nerve was transferred to the thoracodorsal nerve in two cases, with recovery of the latissimus dorsi to M4 in one case. The total muscle recovery rate (up to M3) of the series was 60 percent, and the sensory recovery rate (S3) was 78 percent. Outcomes were related to patient age, operative delay, and whether or not the ulnar nerve was used as a bridge for transfer.

Adolescent↗
PubMed1998

Mother-to-infant transmission of GB virus C/hepatitis G virus: the role of high-titered maternal viremia and mode of delivery.

To study mother-to-infant transmission of GB virus C/hepatitis G virus (GBV-C/HGV), blood samples of infants born to carrier mothers were collected beginning 3 months after birth and were tested for GBV-C/HGV RNA until 1 year of age. Of 2046 mothers, 2.1% were positive for GBV-C/HGV RNA, and 25 of their infants were followed for a median of 12 months. Thirteen infants (52%) were viremic, and infection became persistent in all. Maternal GBV-C/HGV RNA levels of this group were >10(7) copies/mL. Nucleotide sequence comparison in 5 viremic mother-infant pairs revealed a homology of 93%-98.2%, and none delivered by elective cesarean section. In comparison, of the 12 uninfected infants' mothers, 10 had lower GBV-C/HGV RNA levels (mean, 5 x 10(4) copies/mL), and the remaining 2 high-titered mothers had elective cesarean section. Thus, high-titered maternal viremia and mode of delivery are closely associated with the mother-to-infant transmission of GBV-C/HGV to infants, and the infection usually becomes persistent.

Carrier State↗
PubMed1998

GB virus C/hepatitis G virus infection in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: GB virus C or hepatitis G virus (GBV-C/HGV) can be transmitted parenterally, very likely sharing common routes of transmission with hepatitis C virus (HCV). Patients on maintenance haemodialysis have been shown to be at increased risk of the novel GBV-C/HGV infection. Whether continuous ambulatory peritoneal dialysis (CAPD) can reduce the risk of GBV-C/HGV infection as demonstrated for HCV remains unknown. METHODS: Serum GBV-C/HGV RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) with nested primers derived from the 5'-untranslated region (5' UTR) of the viral genome. We investigated the prevalence of GBV-C/HGV viraemia in 60 patients on CAPD and the possible routes of transmission. One hundred healthy adults were selected as controls. RESULTS: The prevalence of GBV-C/HGV viraemia in CAPD patients was 23.3%, compared with 1% of healthy adults (P<0.05). Compared with patients without hepatitis B virus (HBV), HCV or GBV-C/HGV infection (n=39), those with GBV-C/HGV infection alone (n=11) have received more blood transfusions (mean 18.9 units vs 6.8 units, P<0.05). There were no significant differences between the viraemic and nonviraemic groups with respect to age, gender, duration of CAPD, duration of previous haemodialysis, previous history of surgery and co-infection with HBV or HCV. Three of the 11 (27.3%) patients with GBV-C/HGV infection alone had elevated serum alanine aminotransferase (ALT) level, and the frequency was significantly higher than that of patients negative for the viraemia (0%, P<0.05). In addition, the mean serum ALT level was also higher in the group with GBV-C/HGV infection compared with those without HBV, HCV and GBV-C/HGV infections (22.3+/-16.9 U/l vs 14.0+/-6.8 U/l, P<0.01). CONCLUSIONS: Patients on CAPD are at increased risk of GBV-C/HGV infection, and the risk parallels the number of previously transfused units of blood.

Adolescent↗
PubMed1998

Clinical impact of screening first-degree relatives of patients with hepatocellular carcinoma.

Family history is a risk factor for hepatocellular carcinoma (HCC). However, the risk of first-degree relatives is not known. To investigate the risk of HCC among the first-degree relatives of probands and whether screening can lead to early diagnosis of HCCs in these relatives, we conducted a screening program. The probands' first-degree relatives who were >20 years old were included. Serum aminotransferase, hepatitis viral marker, alpha-fetoprotein, and abdominal sonography were done. HCCs were found in 20 (1.9%) of the 1,046 first-degree relatives, especially in the male siblings. Eighty-five percent of these 20 HCC patients were hepatitis B virus carriers. Forty percent of these 20 HCC patients had tumors <5 cm. Approximately 55% of these 20 HCCs were resectable. The 1-year survival rate in these 20 HCC patients with resectable HCCs was 72.7%. However, the overall 1-year survival rate was only 40%. We found HCC in 1.9% of the first-degree relatives of HCC patients. The male relatives, especially the older brothers, were the group at highest risk. The familial HCCs were closely related to the hepatitis B virus infection. To detect HCCs early, initial screening should be done as early as possible on the HCC family members.

Adult↗
PubMed1998

Femoral nerve transfer for treatment of brachial plexus root avulsion.

Femoral nerve transfer to the muscular branches of the thenar and hypothenar muscles was performed to determine its protective effect on the hand intrinsic muscles. Seven cases of brachial plexus root avulsion treated from May of 1989 to October of 1991 were involved. The femoral nerve transfer to the muscular branches of the thenar and hypothenar muscles was done at the same stage of multiple neurotization. The muscular branches derived from the femoral nerve were isolated and coapted with the thenar muscle branch of the median nerve and the deep branch of the ulnar nerve. A groin flap was harvested simultaneously to form a skin-tube pedicle that covered the nerve bridge. At the second stage, when regeneration of the median and ulnar nerves was found to reach as far as the level of the wrist, the femoral nerve was divided and the muscular branches of the thenar and hypothenar muscles were anastomosed with the regenerated median and ulnar nerves. All the cases were followed up for more than 6 years. Six months after femoral nerve transfer, muscle power of the interosseous muscles and adductor pollicis recovered to MRC3, whereas that of the abductor pollicis brevis recovered to MRC1 to 2. Five cases underwent second-stage transfer. Four to five years of follow-up revealed that the muscle power of the interosseous muscles and adductor pollicis was MRC2 in one case, MRC1 in three cases, and MRC0 in one case. As for the donor area, muscle power of the quadriceps femoris reduced to M3 to 4 within 1 month after femoral nerve transfer and recovered to normal at 3 months. In conclusion, femoral nerve transfer to the muscular branches of the thenar and hypothenar muscles has some protective effect on the hand intrinsic muscles. The outcome of the second stage, however, is not satisfactory.

Adolescent↗
PubMed1998

Characteristics of hepatocellular carcinoma presenting with variceal bleeding.

Patients with hepatocellular carcinoma may present with variceal bleeding as the initial symptoms. The aims of this study is to investigate the characteristics of such patients. A total of 1046 hepatocellular carcinoma cases were retrospectively retrieved from our computer records between 1980 and 1993. The medical records and image studies were reviewed. The status of each patient was assessed at the time of presentation. A total of 14 (about 1 %) patients with hepatocellular carcinoma presented with variceal bleeding. Five (36%) did not have past history of liver disease. The tumour size ranged from 2.5 to 11.3 cm. Compared with hepatocellular carcinoma patients not presenting with variceal bleeding, these patients had a higher percentage of portal vein thrombosis (57.1 vs 19.4%). In two patients, the hepatic tumours were missed in the initial abdominal sonography. The average survival time was 71 days. Seven patients died within 2 months mainly due to variceal bleeding (41.6%). Variceal bleeding might be a clue to the presence of hepatocellular carcinoma with portal vein thrombosis even in patients without a previous history of liver disease. The tumours in such patients might be the infiltrative type, and thus the portal vein should be carefully worked-up. Overall, these patients have an extremely poor prognosis. In the management of patients with variceal bleeding, the possibility of hepatocellular carcinoma with portal vein thrombosis should not be overlooked, especially in areas where this cancer is prevalent.

Carcinoma, Hepatocellular↗