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Biomedical subjects

D S Chen

Publications and source records attributed to D S Chen.

At least 145 records · Page 8Linked to original sources

Ontogeny of copepod predation in juvenile squid (Loligo opalescens).

Copepods are the major prey of juvenile squid, and small species of squid such as Loligo opalescens face a great challenge in catching these erratically moving crustaceans. We studied the ontogeny of copepod predation in laboratory-reared animals and found that mastery of copepod capture develops progressively, starting shortly after hatch with strong attacks of a simple type. Modifications of the initial basic attack lead to more specialized strategies that effectively extend the range of capture to both longer and shorter distances. This progression culminates, by approximately 40 days post-hatching, in adult-like prey capture behavior involving tentacle extension and retraction. Squid raised exclusively on easily captured Artemia nauplii and introduced to a copepod diet 40 days after hatching displayed only basic attack behavior, characteristic of very young squid. All of these attacks were unsuccessful, and very few of these animals survived the transition. Copepod capture thus appears to be a skill that must be acquired in an experience-dependent manner early in post-hatching life.

Animals↗

Clinical significance of serum hepatitis C virus titers in patients with chronic type C hepatitis.

OBJECTIVES: To investigate the relationship between serum hepatitis C virus (HCV) titers and clinicopathological characteristics of chronic type C hepatitis. METHODS: Serum HCV cDNA concentrations were determined by a competitive polymerase chain reaction assay in 60 Taiwanese patients with chronic type C hepatitis. RESULTS: The concentration of serum HCV cDNA ranged between 10(2) and 10(8) copies/mL. The titers of serum HCV (logarithmic transformed copies of HCV cDNA/mL serum) were not significantly correlated with clinicopathological characteristics with respect to either sex of the patients, source of infection, higher serum ALT level (>150 IU/L) or histological severity. In contrast, serum HCV titers were significantly higher in patients with age above 50 yr and with type 1b HCV infection. Moreover, the influence of advancing age on serum HCV titer was genotype-independent by multivariate analysis. CONCLUSIONS: These results suggest that advancing age and genotype are both important determinants of HCV viremia and that the pathogenesis of HCV infection might not be caused by direct cytotoxicity of the virus.

Adult↗

Viral hepatitis in East Asia.

Viral hepatitis has a high prevalence in East Asia and is an important problem. Identification of the individual hepatitis viruses. A-E, has enabled researches to investigate the epidemiology and pathogenesis of viral hepatitis and its sequelae, and possible means of prevention. Because of improvement in hygiene in East Asia in recent decades, hepatitis A virus infection has decreased markedly. However, this has resulted in the younger population being susceptible to hepatitis A. Fortunately, effective active immunization for hepatitis A has become available. Hepatitis B is still rampant, especially in the southern part of East Asia where chronic infection is common. Patients who are chronic hepatitis B virus carriers are reservoirs for the virus and have a much higher risk of chronic liver disease and hepatocellular carcinoma (HGC). Currently, hepatitis B infection is being brought under control in East Asia through mass immunization. Serologic and molecular epidemiologic studies have also revealed that Hepatitis C is prevalent in the region. Hepatitis C virus also contributes to the development of cirrhosis and HCC. No effect immunization is currently available, and hepatitis C can only be controlled by preventative measures. The epidemiology and pathogenesis of viral hepatitis is discussed in this review, including new viral hepatitis agents possibly responsible for non-A-E hepatitis.

Chronic Disease↗

Serotypes, genotypes and levels of hepatitis C viremia in pregnant women in Taiwan.

The correlation between a new serotyping method for grouping different genotypes of hepatitis C virus (HCV) and those identified by a polymerase chain reaction (PCR) assay with type-specific primers was investigated in 3,400 pregnant women. The correlation between HCV genotypes and serum HCV levels in HCV-positive pregnant women was studied as well. The new serologic assay used an enzyme-linked immunosorbent assay (ELISA) based on highly group-specific recombinant peptides (C14-1 and C14-2) within the NS4 region and detected group-specific antibodies against different HCV genotypes. Serum HCV levels were assayed by a competitive PCR method. In all, 43 pregnant women were found to be positive for HCV antibodies by the second-generation ELISA method and were positive for HCV-RNA by PCR with primers from the 5' untranslated region. All 43 had defined genotypes: 28 (65%) with HCV 1b, 11 (26%) HCV 2a, 3 (7%) HCV 2b and 1 (2%) HCV 1b + 2a. In 40 (93%) of the 43 viremic pregnant women, the results of serotyping by ELISA showed complete agreement with those determined by PCR genotyping, and none of the women showed a group different from that of the HCV genotype. In addition, serum levels of HCV 1b were significantly higher than those of HCV 2a. The results show that this new serotyping assay is highly sensitive and specific for the determination of HCV genotypes and that serum HCV levels in pregnant women with genotype 1b are higher than those with genotype 2a.

DNA, Viral↗

Transmission of hepatitis C virus between spouses: the important role of exposure duration.

OBJECTIVES: Although interspousal transmission of hepatitis C virus (HCV) has been studied, the factors responsible for it remain unclear. METHODS: To investigate the transmission of HCV between spouses and the related risk factors, 100 anti-HCV-positive index patients and their spouses were studied. RESULTS: Overall, anti-HCV was detected in 17 (17%) spouses, 15 of whom were also positive for HCV RNA, and 11 couples were infected with the same genotype. The anti-HCV-positive rate was higher in spouses married longer than 20 yr compared with those married less than 20 yr (22 vs 6%, p < 0.05), and the infection was correlated with the duration of their actual exposure to the index patients but not with serum HCV titers. The infected couples had more frequent sexual contacts and more commonly shared tooth-brushes than those with uninfected spouses. CONCLUSION: Spouses of patients with chronic hepatitis C have a higher risk of acquiring HCV that increases with longer marriage and duration of exposure, and they should be educated about how to avoid contracting HCV infection from their spouses.

Female↗

A pregnancy-specific glycoprotein is expressed in the brain and serves as a receptor for mouse hepatitis virus.

Mouse hepatitis virus (MHV), a murine coronavirus known to cause encephalitis and demyelination, uses murine homologues of carcinoembryonic antigens as receptors. However, the expression of these receptors is extremely low in the brain. By low-stringency screening of a mouse brain cDNA library, we have identified a member of the pregnancy-specific glycoprotein (PSG) subgroup of the carcinoembryonic antigen gene family. Unlike other PSG that are expressed in the placenta, it is expressed predominantly in the brain. Transfection of the cDNA into COS-7 cells, which lack a functional MHV receptor, conferred susceptibility to infection by some MHV strains, including A59, MHV-2, and MHV-3, but not JHM. Thus, this is a virus strain-specific receptor. The detection of multiple receptors for MHV suggests the flexibility of this virus in receptor utilization. The identification of this virus in receptor utilization. The identification of a PSG predominantly expressed in the brain also expands the potential functions of these molecules.

Amino Acid Sequence↗

Improved gene expression by a modified bicistronic retroviral vector.

We have previously described the construction of a bicistronic retroviral vector using the picornavirus internal ribosome entry site (IRES), which allows two genes expression simultaneously from a single transcript. This vector transcribes RNA efficiently; however, in some cases the levels of protein production are low. In this report, we further modified the bicistronic vector by abolishing the functional viral gag initiation codon that is retained in the vector at 5' to the first initiation codon of transduced gene. Five different genes, human interleukin 2 (hIL-2), human interleukin 4 (hIL-4), human granulocyte macrophage stimulating factor (hGM-CSF), herpes simplex virus thymidine kinase (HSV-tk) gene, and hepatitis C virus (HCV) core gene (C190), were tested on this modified vector for gene transfer and expression. Our results demonstrated that the new bicistronic vector greatly increased the protein levels when compared with the original one. As the RNA levels and splicing patterns from these two vectors remained similar, the improvement was most likely resulted from the increased translational efficiency.

Animals↗

Lack of critical domains in the beta-chain of hepatocyte growth factor.

Hepatocyte growth factor (HGF) is a cytokine with pleiotropic effects on many different cell types. Its biological activities depend on the disulfide-linked alpha beta heterodimeric molecule. To study the functions of the beta-chain of HGF, insect cell-expressed HGFs prepared from nested deletions from C-terminus of beta-chain were studied for their biological activities and ligand-binding functions. The results demonstrated that the functions of HGF are dependent on the intactness of its beta-chain. The loss of HGF activities is correlated with the progressive deletion of beta-chain. There is not a single critical domain in the beta-chain that is essential for the functions of HGF. We propose that beta-chain may act to stabilize the ligand-receptor binding or contribute to the proper conformation of HGF to interact with its receptor.

Animals↗

Unbiased usage of T-cell receptor beta variable region genes in peripheral blood cells of hepatitis C patients: no correlation with superantigen effect.

Hepatitis C virus (HCV) infection frequently causes chronic hepatitis and lack of virus clearance in these patients. In addition, many patients infected by HCV also present with hypergammaglobulinemia in the early stage of chronic infection. These observations raise a possible viral superantigen effect induced by HCV, because viral superantigen found in human immunodeficiency virus (HIV) or in replication of defective murine leukemia virus (MuLV) is associated with T-cell dysfunction and polyclonal activation of B cells. The possibility was investigated of whether HCV encodes any superantigen by analyzing the usage of T-cell receptor (TCR) from the peripheral blood lymphocytes (PBL) of patients with chronic hepatitis C. Two groups, one with hypergammaglobulinemia and the other without hypergammaglobulinemia, were studied for the usage of TCR beta chain by reverse transcription-polymerase chain reaction (RT-PCR) analysis. It was found that all genes of V beta variable chain were used in the PBL of these patients. Furthermore, there was no significant difference of the TCR expression pattern between these two groups, nor a complete deletion of a particular T-cell subset in either group. These results do not provide evidence for HCV superantigen, but indicate that the TCR usage in the patients was neither defective nor biased.

Adult↗

Intrafamilial transmission of hepatitis C virus in hemodialysis patients.

The prevalence of hepatitis C virus (HCV) infection in chronic hemodialysis patients ranges from 20 to 50% and these patients may serve as a reservoir of infection for their household contacts. The aim of this study was to investigate the prevalence of anti-HCV in hemodialysis patients and their families, and to evaluate possible routes of infection. One hundred eighty-six family members of 84 hemodialysis patients and 529 healthy adults were enrolled. The family members consisted of 50 spouses, 96 children, 11 parents, 29 siblings, and other relatives living together with the patients. Serum samples were collected for testing anti-HCV. Exposure to risk factors was obtained by a questionnaire and an interview. The results showed that prevalence of anti-HCV in hemodialysis patients was 44%, whereas in family members it was 5.4%, not significantly different from that of age-matched healthy adults (standardized morbidity rate = 1.51, P = 0.390). The anti-HCV rate in family members tended to increase with age, and a spouse of an infected hemodialysis patient had a higher risk of HCV infection than other family members (15% vs. 2.6%, odds ratio 6.6, P = 0.058). Except for the age factor, no difference was found between seropositive and seronegative family members with respect to risk factors such as blood transfusion, surgery, frequent injections, dental procedures, or acupuncture. It was concluded that, although the anti-HCV positivity of hemodialysis patients is high, the risk of HCV infection for their family members is not higher than that of the general population. Among family members, spouses of seropositive hemodialysis patients have the highest risk of HCV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Quantitative detection of hepatitis B virus DNA in human sera by branched-DNA signal amplification.

Serum samples from 116 patients with hepatitis B surface antigen (HBsAg), from 7 patients without detectable HBsAg and from 71 healthy blood donors were tested by a branched DNA signal amplification (bDNA) method. Hepatitis B virus (HBV) DNA was detected in 39 (34%) of the 116 samples with HBsAg, including 19 (70%) of the 27 patients who were also positive for hepatitis B e antigen (HBeAg). In contrast, one of the 7 patients without HBsAg and none of the 71 blood donors were positive for HBV DNA. The titers of serum HBV DNA did not correlate with the serum alanine aminotransferase levels. All the samples positive by the bDNA assay were positive by the polymerase chain reaction (PCR). However, 59% of the PCR-positive samples were bDNA-negative. None of the PCR-negative samples was positive by the bDNA method. Although the sensitivity of bDNA method is not entirely satisfactory, it showed excellent specificity and reproducibility. Thus it may be considered as an alternative for quantitative detection of HBV DNA in serum samples of patients with relatively high titers of HBV viremia.

Adolescent↗

Absence of infection in breast-fed infants born to hepatitis C virus-infected mothers.

The role of breast-feeding in perinatal transmission of hepatitis C virus (HCV) was explored in 15 HCV-infected mothers and their infants. The 15 carrier mothers had anti-HCV titers ranging from 1:80 to 1:40,000 and also had HCV-ribonucleic acid with concentrations ranging from 10(4) to 2.5 x 10(8) copies/ml. Both anti-HCV antibody and HCV-ribonucleic acid were present in colostral samples in much lower levels, but none of the 11 breast-fed infants had evidence of HCV infection for up to 1 year of age. Thus breast-feeding seems safe for these infants.

Breast Feeding↗

Long-term expression of the biologically active growth hormone in genetically modified fibroblasts after implantation into a hypophysectomized rat.

We employed the hypophysectomized rats as an animal model to explore the feasibility of using genetically engineered fibroblast cells for growth hormone gene therapy. An internal ribosome entry site (IRES)-directed bicistronic retroviral vector, PSN, which contained a porcine growth hormone (pGH) cDNA at the first cistron and a Neo(r) gene at the second cistron was used to infect primary rat embryo fibroblast (REF) cells. The infected cells (5 x 10(6) cells/rat) were injected directly into the peritoneum of syngeneic hypophysectomized rats. We demonstrate that the implanted PSN-infected REF cells could secrete biologically active pGH in vivo, leading to significant growth of the tibia at day 15 and day 57 post-implantation. We also treated the PSN-infected REF cells with collagen to form a tissue-like structure. The skin-like discs were grafted underneath the skin on the back of rats and cells were retrieved at different times. Using two criteria, semiquantitative reverse transcription-polymerase chain reaction on the pGH RNA extracted from the explants and G418 resistance conferred from the explanted cells, we demonstrate that pGH was expressed in the implanted fibroblasts up to 70 days. Despite the fact that the total pGH RNA level was reduced in the explants of long-time post-implantation, which was probably due to the reduction of transduced cells retained in the explants, the specific efficiencies of pGH RNA expression from these explants were maintained as high as the primary PSN-infected REF prior implantation. These results suggest that fibroblast cells are capable of expressing the foreign genes persistently in vivo.

3T3 Cells↗

Evaluation of third-generation hepatitis C antibody assay in chronic hepatitis C and chronic non-B, non-C hepatitis.

Second-generation hepatitis C virus (HCV) antibody assays are more sensitive and specific than first-generation assays in the detection of HCV infection; such tests are widely used. However, there are still HCV-infected patients who test seronegative for anti-HCV even by second-generation assays. In this study we evaluated the performance of the new third-generation HCV assay (HCV 3.0) in 230 individuals with different second-generation anti-HCV (HCV 2.0) and HCV RNA patterns. Our results showed the followings: only one healthy adult had a discrepant result in 200 subjects negative (group I) or positive (group II) for HCV 2.0 and HCV RNA; 7 of 13 (54%) HCV 2.0-negative but HCV RNA-positive patients (group III) were HCV 3.0-positive; two of 17 (12%) so-called chronic non-B, non-C hepatitis patients (group IV) were positive for HCV 3.0. We conclude that third-generation anti-HCV assays are more sensitive and specific than second-generation assays in the detection of chronic HCV infection; however false-positive results may be observed among low-risk healthy persons.

Adult↗

Precore mutant of hepatitis B virus in childhood fulminant hepatitis B: an infrequent association.

Serum HBV DNA from infants and children with fulminant hepatitis B (FHB) or acute self-limiting hepatitis B (AHB) and patients believed to be contamination sources was amplified by polymerase chain reaction (PCR) followed by direct sequencing of the precore region. A precore mutation from G to A at nucleotide 1896 was found in 5 of 14 FHB patients and in 3 of 10 AHB patients. Among the 10 infants who developed hepatitis during the first 6 months of age, the precore mutation was detected in only 2 of 7 with FHB and in 1 of 3 with AHB. In 1 infant with FHB, a shift from wild type to precore mutant predominance occurred in the serum virus population during the incubation period. Thus, the precore mutation is neither necessary nor sufficient to cause FHB in childhood, although its contributory role cannot be excluded. Factors other than precore mutations may be important in the pathogenesis of FHB.

Acute Disease↗

Quasispecies of hepatitis C virus and genetic drift of the hypervariable region in chronic type C hepatitis.

The sequential variations of amino acid sequences in the hypervariable region (HVR)-1 of hepatitis C virus (HCV) and changes of viremia in 2 patients with different clinicopathologic courses of chronic hepatitis C were studied. By using polymerase chain reaction amplification, cloning, and sequencing of HVR-1, genetic heterogeneity of HCV was shown. The highest annual rate of consensus amino acid variation per 100 sites in HVR-1 of a patient with acute exacerbation was 15.4 versus 2.3 in a patient without acute exacerbation. The serial serum HCV titers were also quantified. An abrupt elevation of serum titer was associated with acute exacerbation, whereas constant viremia was observed when acute exacerbation did not occur. These results show that a quasispecies of HCV exists and patients with different courses of chronic hepatitis may have different sequential changes in virus titer and genetic drift of HVR-1.

Aged↗

Early interferon therapy and abortion of posttransfusion hepatitis C viral infection.

We studied the role of an "early" 4-month course of interferon therapy on posttransfusion viral hepatitis C (PTH-C). Paired serum samples of 51 consecutive recipients, taken before and 7-20 days after blood transfusion, were prospectively tested for hepatitis C virus ribonucleic acid (HCV RNA) using the polymerase chain reaction assay. Seven recipients experienced seroconversion of HCV RNA after transfusion. Two of the seven patients underwent an early 4-month course of interferon alpha therapy at a dose of 3 mU per day for 5 days during the first week, then three times a week for the subsequent 15 weeks. The first patient was treated at a very early stage of acute PTH-C and responded well to interferon therapy. Acute PTH-C in the second patient was prevented by interferon therapy. Both patients had normal serum alanine aminotransferase levels and tested negative for anti-HCV and HCV RNA 12 months after the end of treatment. Four of the five patients not on interferon therapy developed abnormal serum alanine aminotransferase activities more than five times the normal upper limit (383 +/- 143 IU/L) at 2-18 weeks after transfusion. All four patients experienced seroconversion of anti-HCV, and three patients developed chronic hepatitis. This study suggests that early long-term interferon therapy has the potential to prevent PTH-C.

Adult↗