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T S Su

Publications and source records attributed to T S Su.

At least 37 records · Page 2Linked to original sources

Elevation of facilitated glucose-transporter messenger RNA in human hepatocellular carcinoma.

Complementary DNA of a rat brain glucose transporter gene was used to examine the expression of glucose-transporter messenger RNA in paired human hepatocellular carcinomas and adjacent nontumorous liver tissues, as well as in human hepatoma cell lines and human fetal liver samples. High expression of a major 2.8-kilobase glucose-transporter transcript was seen in all hepatoma cell lines and fetal liver samples examined, whereas a much lower level of expression was observed in liver tissues. When pairs of liver tissues were examined, elevation of glucose-transporter RNA levels was observed in most of the hepatocellular carcinoma tissues examined.

Animals↗

Phenylketonuria mutation in Chinese haplotype 44 identical with haplotype 2 mutation in northern-European Caucasians.

DNA amplification with the polymerase chain reaction was employed to identify the phenylketonuria (PKU) mutation in Chinese PKU families. The amplified DNA was hybridized with oligonucleotides corresponding to the two most common mutant alleles, i.e., mutations associated with PKU haplotype 2 and 3 among Caucasians of northern-European ancestry. The results of analysis demonstrate that the mutation in Chinese haplotype 44 is a single-base substitution corresponding to the mutation associated with haplotype 2 in Caucasians, whereas the mutations of the phenylalanine hydroxylase gene in haplotypes 4, 7, 11 and 28 among Chinese do not correlate with either of the two mutations identified in northern-European Caucasians.

Asian People↗

Encapsidation of truncated human hepatitis B virus genomes through trans-complementation of the core protein and polymerase.

Mutational analyses and complementation tests were used to analyze the strategy of packaging and of replication of human hepatitis B virus (HBV). By creating new restriction enzyme sites and by varying the genome length of HBV mutants, we identified that the mutated genomes could be encapsidated through trans-complementation of the polymerase and/or core protein. This study demonstrates that the polymerase of HBV, similar to that of duck hepatitis B virus (DHBV), is synthesized de novo instead of through a core-polymerase fusion protein. The results also indicate that both the polymerase and the core protein can be supplied in trans during viral packaging, and that the complementation is not due to recombination between the cotransfected plasmids. Furthermore, HBV genome deleted down to 2.4 kb is still able to be encapsidated, as measured by the endogenous polymerase reaction. Taken together, these results provide a basis for using HBV as a vector to deliver foreign genes into hepatocytes and for defining the location of the packaging signal on the HBV genome.

Capsid↗

Insulin suppresses hepatitis B surface antigen expression in human hepatoma cells.

The human hepatoma Hep3B cells contain integrated hepatitis B viral genome and continually secret hepatitis B surface antigen (HBsAg). The production of HBsAg (but not alpha-fetoprotein) was suppressed by addition of low concentrations (0.1-1 nM) of insulin into serum-free medium. In addition, the suppression of HBsAg production by insulin was paralleled with the decrease in HBsAg mRNA abundance. Insulin also cause a rapid rate of disappearance of HBsAg mRNA (t 1/2, 2 h) in Hep3B cells. The Hep3B cells carry specific receptor with high affinity for insulin (Kd = 1.8 nM). The receptor showed an insulin-dependent protein tyrosine kinase activity. The half-maximal insulin concentration for the activation of the receptor kinase was about 5 nM. Only very high concentrations of insulin-like growth factor I and human proinsulin can compete for the insulin receptor binding and suppress HBsAg production, this suggests that insulin may act through its receptor binding to suppress HBsAg expression in human hepatoma Hep3B cells.

Blotting, Northern↗

Transcripts of the insulin-like growth factors I and II in human hepatoma.

Using complementary DNAs of human insulin-like growth factors as probes, expressions of the insulin-like growth factors I and II mRNA were examined in seven human hepatoma tissues and their adjacent nontumorous livers. The level of insulin-like growth factor I mRNA in hepatoma was lower than that in the nontumorous liver control. This phenomenon was probably caused by the low expression of human growth hormone receptor in hepatoma tissues. The levels of insulin-like growth factor II mRNA vary among hepatomas. Some show elevated expression; some have diminished expression compared to their nontumorous liver counterparts. In four of the seven hepatomas, expression of fetal forms of insulin-like growth factor II transcripts was observed and may represent dedifferentiation of insulin-like growth factor II expression during hepatocarcinogenesis.

Carcinoma, Hepatocellular↗

Analysis of hepatitis B virus transcripts in infected human livers.

The hepatitis B virus transcripts in human hepatoma and its adjacent nontumorous liver were examined with probes specific to hepatitis B virus surface antigen, core antigen, X region and pre-S region. The study shows that the patterns of hepatitis B virus transcripts for tumorous tissue and the counterpart in nontumorous liver differ. In most of the tissues examined, the surface antigen gene is transcribed. Most of these transcripts, besides having surface antigen sequences, also have an X region; some also include a pre-S region. The transcripts that hybridized to a core-specific probe were a pair of poly(A+) RNA, 3.5 and 2.2 kilobases in size, present in two of the nontumorous hepatocytes where the virus was actively replicating. The 3.5-kilobase transcript not only hybridized to the core probe, but was able to be hybridized to other hepatitis B virus subgenomic probes and might represent the RNA pregenome involving hepatitis B virus DNA replication. Whereas most of the transcripts hybridizable to hepatitis B virus probe are in the size range of 2.1 to 2.7 kilobases, some transcripts other than the pregenomic RNA appear to be greater than 3.2 kilobases in size and may represent the hybrid RNAs of viral and host sequences.

Blotting, Northern↗

Study of restriction fragment length polymorphisms at the human phenylalanine hydroxylase locus and evaluation of its potential application in prenatal diagnosis of phenylketonuria in Chinese.

Using a human phenylalanine hydroxylase cDNA probe, the restriction fragment length polymorphisms at the human phenylalanine hydroxylase locus have been determined with the restriction enzymes BglII, PvuII, EcoRI + BamHI, MspI, XmnI, HindIII and EcoRV. The frequency of the observed heterozygosity of the restriction site polymorphisms at this locus in a Chinese population is approximately 54%, which is significantly lower than that in Caucasians. No DNA rearrangement or deletion of the phenylalanine hydroxylase locus was detected among mutant phenylalanine hydroxylase genes in seven Chinese classical phenylketonuria (PKU) families. Haplotype analysis of these seven families revealed that the mutant alleles belonged to five different haplotypes, i.e. haplotype 4, 11 and three unreported haplotypes. The majority of normal and mutant phenylalanine hydroxylase genes are confined to hyplotype 4. These results indicate that approximately 42% of Chinese PKU families are informative for prenatal diagnosis of PKU when eight restriction sites linked to the phenylalanine hydroxylase locus are examined.

Alleles↗

Hepatitis B virus transcript produced by RNA splicing.

A new hepatitis B virus (HBV) transcript of about 2.2 kilobases was identified in HBV DNA-transfected human hepatoma cells. The 5' terminus of this viral RNA appears to map at one or more of the precore initiation sites, contains a deletion of 1,223 bases corresponding to the last codon of the core gene to the middle of the surface antigen gene, and terminates at the 3' polyadenylation site used by the other known HBV RNAs. The junction region of the deleted sequences showed the conserved splice donor and acceptor GT-AG sequences. Moreover, when a mutant HBV DNA in which the splice acceptor site was changed from AG to CG was transfected into human hepatoma cells, no 2.2-kilobase RNA was detected, further suggesting that this RNA represents a spliced transcript. The core gene, although an amino acid shorter, still encoded a functional viral core protein in complementation experiments. Sequence analysis of the cDNA of the 2.2-kilobase RNA suggests that this transcript can potentially encode a new protein that comprises the reverse transcriptase domain of HBV. However, genetic analysis using a transient DNA transfection system suggests that the gene product(s) of this transcript is not essential for viral replication. The function of this transcript remains to be studied.

Base Sequence↗

Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.

Previous reports indicate that human hepatocytes do not express class I and class II MHC antigens. Our analyses on 10 human hepatocellular carcinoma (HCC) cell lines by immunofluorescence tests and RIA, demonstrate that all the human HCC cell lines tested express class I MHC antigens and among them, three poorly differentiated human HCC cell lines also express class II MHC antigens. Results of immunoprecipitation and/or Western blotting experiments indicate similarity in the chemical nature of both the class I and class II MHC antigens expressed by the human HCC cell lines and by a human B lymphoblastoid cell line Raji. Furthermore, a new variant form of class I antigen was detected in some of these HCC cell lines. Immunohistochemical studies of HCC tissues using the peroxidase-antiperoxidase staining method indicated that class I and class II antigens were detectable in 7 out of 11 and 3 out of 11 HCC tissues from patients, respectively. The availability of MHC class I antigen-positive cultured HCC cell lines, including the poorly differentiated lines that also express MHC class II antigen, has provided us with interesting models to study the relationship between expression of MHC antigen and transformation and differentiation of human hepatocytes. These studies will also allow us some insight into the role of MHC class I and class II antigen in the immunosensitivity and immunogenicity of HCC cells to the host-immune response.

Blotting, Western↗

Serum TSH, FT3, and FT4 levels in inhabitants of an endemic goiter area in China supplied iodized salt for twenty-five years.

The thyroid function and TSH concentration of villagers in an endemic goiter area in China where iodized salt had been supplied for twenty-five years were surveyed. We found that the serum FT3 and TSH (IRMA) levels of villagers were higher and the FT4 levels was lower than those of the controls, which suggested that the inhabitants of the endemic goiter area had subclinical hypothyroidism based on the ultrasensitive method for TSH assay. Therefore, we suggest that the best biochemical techniques for monitoring the iodized salt prophylaxis program and the physiological response of villagers to iodine are measurements of serum TSH level and FT4 level periodically.

Adolescent↗

Evidence of autocrine regulation in human hepatoma cell lines.

Human hepatoma cell lines were studied for the expression of platelet-derived growth factor (PDGF), insulin-like growth factor-I (IGF-I) and their receptors at the mRNA level. Transcripts of PDGF were consistently detected in these cell lines. In addition, some cell lines also expressed PDGF receptor RNA. Moreover, RNA of IGF-I and its receptor were detected in every cell line examined. These results suggest that autocrine regulation may be an important mechanism for the maintenance of the transformed state of human hepatoma cells.

Carcinoma, Hepatocellular↗

Assessment of HBV persistent infection in an adult population in Taiwan.

In order to study the prevalence of hepatitis B virus (HBV) in the adult population of Taiwan, we screened for the presence of HBV DNA in 205 blood samples from adult (20-59-year-old) volunteers. According to the serological markers of HBV, samples were divided into three groups: group I (173 subjects) was negative for both HBsAg and HBeAg; group II (14 subjects) was positive for both HBsAg and HBeAg; and group III consisted of 18 subjects who were HBsAg-positive but HBeAg-negative. Plasma HBV DNA was not detected in group I, but it was found in 85.7% and 11.8% of samples in group II and group III, respectively. A free-form HBV DNA was found in 14.3% of the leukocyte samples in group II. Furthermore, an integrated form of HBV DNA was detected in the leukocytes of two cases of group I who remained healthy based on clinical data. HBV DNA was also detected in the spermatozoa and liver cells of one of the cases.

Adult↗

Thyroid function of subjects with goitre and cretinism in an endemic goitre area of rural China after use of iodized salt.

Endemic goitre and cretinism are still a public health problem in China. An epidemiological survey showed that about 5% of the inhabitants in Daxin village, Henan province, had goitre or cretinism after an iodized salt prevention programme had been carried out for two decades. The main food for the inhabitants of this area has an iodine content less than 30 nmol/kg and the water for cooking and drinking has an iodine concentration between 7-12 nmol/l. We studied thyroid function in subjects of this village. There were 42 with grade 0 goitre (males 29, females 13), 42 grade I (males 23, females 19), 27 grade II (males 9, females 18), 31 grade III (males 14, females 17) and 34 cretinism patients (males 30, females 4) diagnosed and classified according to WHO criteria. Serum T4, free T4, T3, free T3, T3 uptake, TSH and thyroglobulin were measured in these subjects. The patients with goitre or cretinism had significantly decreased serum free T4 and increased serum T3 and free T3 levels compared with those of controls. Thyroid size was positively correlated with age and serum thyroglobulin concentrations. Serum thyroglobulin was significantly increased even in the grade 0 goitre subjects. The percentages of subjects with serum free T4 less than 12 nmol/l, T3 greater than 2.5 nmol/l, free T3 greater than 5.2 pmol/l, TSH greater than 3.5 mU/l, T3/T4 ratio greater than 0.03 and free T3/free T4 ratio greater than 0.36 were significantly higher among goitre and cretinism patients than among controls. The data suggest that there is partial compensation for a marginal deficiency of iodine in the inhabitants of this village.

China↗

Expression of oncogenes in human hepatoma cell lines.

The expression of 20 known cellular proto-oncogenes in human well-differentiated hepatoma cell line Hep3B and poorly-differentiated hepatoma cell line HA22T/VGH was studied by Northern blot hybridization. Among the cellular proto-oncogenes examined, both cell lines express protein kinase genes including fps, mos and raf; PDGF B chain sis gene; GTP/GDP binding protein gene Ha-ras and nuclear protein genes including fos and myc. The expression of yes, abl, ros, src, erb-B, erb-A, fms, Ki-ras, myb, rel and bas genes was not detected in both cell lines.

Blotting, Northern↗

The enhancer sequence of human hepatitis B virus can enhance the activity of its surface gene promoter.

The transcriptional enhancer sequence has recently been demonstrated in the hepatitis B viral genome. This enhancer sequence has also been shown to increase the activity of HBcAg gene promoter. Using the chloramphenicol acetyltransferase gene expression system, we demonstrated that the intrinsic promoter activity of HBsAg gene promoter was stronger than that of HBcAg gene promoter in both human hepatoma cell lines, Hep3B and HuH-7. Furthermore, we showed that the HBV enhancer sequence not only stimulated the HBcAg gene promoter activity, but also stimulated the HBsAg gene promoter activity in both Hep3B and HuH-7 cells. The enhancer sequence increased the HBsAg gene promoter activity 20-fold in both Hep3B and HuH-7 cell lines, while the increase of the HBcAg gene promoter was 2- and 8-fold in Hep3B and HuH-7 cells, respectively.

Acetyltransferases↗

Production of hepatitis B virus in vitro by transient expression of cloned HBV DNA in a hepatoma cell line.

Transfection of human hepatoma cell lines with cloned HBV DNA resulted in the secretion of large amounts of hepatitis B surface antigen (HBsAg) and core-related antigens (HBc/HBeAg) if well-differentiated cell lines were employed. Synthesis of both viral antigens was the highest in cell line HuH-7 and continued for approximately 25 days. Particles resembling hepatitis B virions (Dane particles) by morphology, density and by the presence of the preS1 surface antigen were released from the transfected HuH-7 cells into the culture medium. These particles produced in vitro were also indistinguishable from the naturally occurring hepatitis B virions in containing the virus-associated DNA polymerase and mature HBV genomes. Restriction analysis of these DNA molecules was compatible with the nucleotide sequence of the transfecting HBV DNA sequence. Viral surface antigens and core proteins present in the culture medium were fractionated and characterized by immunoprecipitation and SDS--PAGE after labeling with [35S]methionine. Antisera specific for X-gene products identified in cell extracts two hitherto unknown HBV gene products. This system thus provides a new approach to open questions regarding HBV-related gene function and HBV replication.

Carcinoma, Hepatocellular↗

Selective suppression of insulin-induced proliferation of cultured human hepatoma cells by somatostatin.

The effects of somatostatin (SRIF), insulin, and triiodothyronine (T3) on the growth of human hepatoma cells were investigated on the well-differentiated human hepatoma cell line Hep3B. Results showed that both insulin and T3 can stimulate cell growth of serum starved Hep3B cells at physiological concentrations. SRIF alone showed little growth-promoting activity. When added concurrently with insulin, however, SRIF suppressed the insulin-induced cell proliferation in a dose-dependent manner. On the other hand, SRIF had no inhibitory effect on T3-induced cell proliferation. SRIF is labile in the medium, with a half-life of about 2 h during culture incubation. SRIF did not disturb the insulin binding to its surface receptors nor inhibit the insulin-dependent receptor kinase activity of Hep3B cells in vitro. These results suggest that postreceptor regulation may be involved. The selective suppression by SRIF of insulin-induced cell growth provides an unique approach to the study of insulin actions on proliferation of human hepatoma cells.

Carcinoma, Hepatocellular↗

Monoclonal antibodies against human esophageal carcinoma cell lines.

Two monoclonal antibodies, designated 4C4 and 4G1, were produced by immunization of BALB/c mice with a human esophageal carcinoma cell line, CE69T/VGH, followed by fusion of the spleen cells from an immunized mouse with myeloma cells NS-1. 4C4 showed strong binding activity to three human esophageal carcinoma cell lines and one human hepatoma cell line, but not to any other cell lines tested. 4G1 reacted with three human esophageal carcinoma cell lines and four other cell lines. By peroxidase-antiperoxidase staining, 4C4 and 4G1 detected antigens of the epithelial cells on 10 pairs of esophageal carcinoma and normal esophageal specimens. 4G1 recognized a CE69T/VGH antigen with a molecular weight of 180K. Since 4G1 also reacted with purified carcinoembryonic antigen (CEA) and immunoprecipitated 125I-CEA, 4G1 seems to be an antibody recognizing CEA produced by CE69T/VGH cells. Since 4C4 also bound to the epithelial cells of normal uterine, vaginal, breast and liver tissues, it seems to recognize an epithelial antigen, and can be used to characterize the antigen in the specialization or differentiation of epithelial cells.

Animals↗