Search PubMed⌕ Search

Biomedical subjects

S H Han

Publications and source records attributed to S H Han.

At least 199 records · Page 11Linked to original sources

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↗

Allergenic components of Candida albicans identified by immunoblot analysis.

Allergenic components of Candida albicans fractionated by SDS-polyacrylamide gel electrophoresis (PAGE) and transferred to nitrocellulose membranes were identified using sera from 30 asthmatic patients who showed positive skin test and RAST (radio-allergosorbent test) to C. albicans. The IgE-binding yeast components in the complex antigen preparation were then detected by reaction with enzyme-labelled anti-human IgE antibodies. They were confirmed by Coomassie blue R-250 staining of the membrane to visualize all protein bands after reaction with the enzyme substrate. The IgE-binding patterns of the sera tested were heterogeneous, displaying a total of 16 identifiable components with molecular weights ranging from 20 to 94 kD. A 40 kD component showed the highest IgE-binding frequency, being recognized by 23 (77%) of the 30 sera examined. The other 15 allergenic components identified were recognized by less than 25% of the sera tested. Only two of the 30 serum samples contained IgE antibodies reactive with seven to eight allergenic components. Ten of the 30 sera reacted with only one allergenic component, and the remaining serum samples recognized two to five of the 16 identified allergens. Results described in this study are applicable to allergen standardization work and provide a basis for further study on the role of C. albicans in clinical allergy.

Antigens, Fungal↗

Presence of catenated human papillomavirus type 16 episomes in a cervical carcinoma cell line.

Human papillomavirus (HPV) is frequently associated with cervical carcinoma and derived cell lines. In primary tissues of the carcinoma, the viral genome may be present in episomal or integrated configuration. In cell lines, however, only integrated HPV sequences have been reported. In this article, we describe the presence of episomal type 16 HPV (HPV16), demonstrated by electron microscopy and two-dimensional agarose gel electrophoresis, in a cervical carcinoma cell line, CC7T/VGH, established in 1980 in Taiwan. In CC7T/VGH, the HPV16 sequences are transcriptionally active, and at least three major HPV16 RNA species were detected in Northern blots. Results from restriction enzyme and S1 nuclease analysis suggest a composition of oligomeric HPV16 molecules in dimeric repeats. In addition, the HPV16 oligomers exist as catenated molecules of interlocking rings instead of concatemers. A monomeric copy of the HPV16 episome was cloned from a Hirt supernatant of CC7T/VGH by using a plasmid vector. Mapping and partial sequencing studies revealed an internal deletion of 163 base pairs within the L1 open reading frame. However, insertion of an A.C nucleotide pair at the deletion junction restored the otherwise frame-shifted L1 open reading frame. Two base transitions were also found within the E7 and the E1 open reading frames. Our findings suggest the need for closer examination for HPV episomal catenation in other cervical carcinoma cell lines as well as in primary carcinoma tissues of the uterine cervix and the anogenital tract. With CC7T/VGH, a way is now available for studies of many important aspects of the biology of HPV such as replication and gene expression of the extrachromosomal viral genome.

Base Sequence↗

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↗

Arrangements of alpha-globin gene cluster in Taiwan.

In a gene mapping study on 217 newborn babies in Taiwan with alpha- and zeta-globin probes, we have observed 4 cases (1.84%) of alpha-thalassemia-2 heterozygotes (zeta zeta-alpha/zeta zeta alpha alpha) without increased levels of hemoglobin (Hb) Bart's in the cord blood. Eleven subjects (5.07%) were found to have the South East Asian alpha-thalassemia-1 haplotype (zeta zeta--SEA/zeta zeta alpha alpha) with increased Hb Bart's levels ranging from 2.2 to 9%. One case, with Hb Bart's level of 14% in the cord blood, was found to have the genotype of zeta zeta--SEA/zeta zeta alpha alpha T (0.46%). Four heterozygotes (1.84%) were found with the triple alpha gene anti-rightward arrangement (zeta zeta alpha alpha alpha 3.7/zeta zeta alpha alpha). Twenty-one heterozygotes (9.68%) were found to have the triple zeta-globin gene arrangement (zeta zeta zeta alpha alpha/zeta zeta alpha alpha). A new triple zeta-globin gene variant with a BamHI polymorphism was also observed in this study.

Asian People↗

In vitro chemosensitivity assay of human urologic malignancies.

An attempt was made to detect the chemosensitivity of fresh specimens of urologic malignancies using a liquid medium culture assay and an agar cloning assay. The sensitivity of cells to anticancer drugs was divided into five grades according to the ratio of cytotoxicity: 0 (0%); 1 (1-25%); 2 (26-50%); 3 (51-75%), and 4 (76-100%). Among the urothelial cancers (36 cases), the sensitivity grade was on the average 2.05 with cisplatin, 2.11 with doxorubicin, 1.49 with endoxan, 1.46 with methotrexate and 1.79 with thiotepa. Higher grade tumor specimens have higher sensitivity to anticancer drugs than lower grade tumor specimens, but there was no correlation between clinical stages and drug sensitivity. Three of 36 cases (8.3%) of transitional cell carcinoma showed complete drug resistance. Simultaneous agar culture clonogenic assays were performed in 7 cases, the results of which were similar to those of the liquid culture method. Three major drawbacks of clonogenic assay are that it is time-consuming, difficult to count, and easy to contaminate. Among 16 cases of kidney tumors, the highest response rate was to thiotepa (2.0) and lowest to endoxan (1.4). No correlation between clinical stage and drug sensitivity could be found. The other five miscellaneous cases all demonstrated moderate sensitivity to those anticancer drugs.

Adult↗

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↗

Alteration of mitogenic responses of mononuclear cells by anti-ds DNA antibodies resembling immune disorders in patients with systemic lupus erythematosus.

Anti-double-stranded DNA antibodies (anti-DNA) purified from pooled active SLE sera by lambda phage DNA-affinity chromatography was found to affect phytohemagglutinin (PHA) and pokeweek mitogen (PWM)-induced responses of normal mononuclear cells. Anti-DNA at a concentration of 0.25 mg/ml (equivalent to 21 units/ml of DNA binding activity) significantly suppressed the PHA-induced [3H]thymidine incorporation of mononuclear cells in 3 days of culture but had no effect on 5-day and 7-day cultures. In contrast, a biphasic effect of anti-DNA on PWM response was found such that early phase (3-day culture) was inhibited whereas late phase (from 5 days to 9 days of culture) was enhanced by the antibodies. Anti-DNA also increased the immunoglobulin synthesis by PWM-stimulated B cells. The inhibition of PHA response in 3-day culture by anti-DNA is not due to changes in T cell subpopulations. Because interleukin 1 (10 units/ml) could restore the PHA response, it appears that anti-DNA suppressed the IL-1 production by monocyte/macrophage. The biphasic effect of anti-DNA on PWM response is the result of monocyte impairment and B cell stimulation by the antibodies. In the early phase (on day 3) the inhibition would seem to be due to impairment of accessory cell function by anti-DNA, though in late phase (after day 5) the anti-DNA may stimulate B lymphocytes to incorporate more thymidine in the presence of PWM. These biological effects of anti-DNA in vitro resemble the in vivo immunologic disorders in patients with SLE, in that impaired cell-mediated immunity and B cell hyperactivity are frequently observed.

Antibodies, Antinuclear↗

Defective helper T cell function in IgM rheumatoid factor synthesis in patients with ankylosing spondylitis.

Despite chronic inflammation and the presence of hypergammaglobulinemia, rheumatoid factor (RF) is rarely found in the blood of patients with ankylosing spondylitis (AS). We used ELISA to compare spontaneous and pokeweed mitogen (PWM)-induced IgG, IgM and IgM rheumatoid factor (IgM-RF) production in normals and in patients with rheumatoid arthritis (RA) and AS. The IgG and IgM synthesis in these three groups did not differ. However, the IgM-RF level in PWM-induced mononuclear cell cultured supernatants of AS was significantly decreased, compared with normal and RA patients. Furthermore, mixing experiments by co-culture of normal T or B cells with patient's B or T cells in the presence of PWM revealed a deficiency of the helper T cell function in patients with AS. These results illustrate the cellular mechanism of the seronegativity of the rheumatoid factor in patients with ankylosing spondylitis.

Arthritis, Rheumatoid↗

Defective phagocytosis, decreased tumour necrosis factor-alpha production, and lymphocyte hyporesponsiveness predispose patients with systemic lupus erythematosus to infections.

Twenty-three patients with systemic lupus erythematosus (SLE) were studied in order to understand the mechanism of increased susceptibility to infection in SLE patients. We found that phagocytosis by polymorphonuclear leucocytes (PMN) was significantly defective in untreated (24.2 +/- 3.1%) and immunosuppressant-treated SLE patients (30.0 +/- 3.6%) compared with normals (47.9 +/- 0.6%), while the generation of superoxide anion radicals was normal. The defective phagocytosis in SLE could be increased by human recombinant tumour necrosis factor alpha (TNF-alpha). However, the percentages of phagocytosis in SLE before and after TNF-alpha stimulation were 56.6% and 60.7% of the normal values. This indicates that certain populations of PMN in SLE are not only defective as regards phagocytosis but also unresponsive to TNF-alpha stimulation. In an ELISA, TNF-alpha production by phorbol myristate acetate (PMA)-stimulated mononuclear cells from SLE patients was significantly decreased (181.4 +/- 22.7 pg/ml vs. 533.0 +/- 81.9 pg/ml, p = 0.002). In addition, the percentage of phytohaemagglutinin (PHA)-stimulated mononuclear cells in S phase in the cell cycle was deficient in patients with SLE (17.2 +/- 1.8% vs. 29.7 +/- 2.9%, p less than 0.001). These results lead us to propose that defective PMN in spontaneous and TNF-alpha-induced phagocytosis, decreased production of TNF-alpha, and lymphocyte hyporesponsiveness predispose patients with SLE to infections.

Adolescent↗

Tumoricidal effect of controlled-release polymeric needle devices containing adriamycin HCl in tumor-bearing mice.

Controlled-release polymeric needle devices containing adriamycin HCL (ADH) were investigated by an in vitro dissolution study in normal saline solution and an in vivo antitumor activity in C3H mice bearing mammary carcinoma and nude mice bearing brain tumor. HPMC was used as a release rate regulator. The ADH released from needle devices was controlled by the types of polymer used and the addition of HPMC. EVA needle devices exhibit a zero order release behavior better than that of PLA needle devices. Tumor growth was markedly inhibited by treatment with needle devices after locally inserted into the solid tumor. The rank of antitumor activity of the needle devices is EVA greater than PLA greater than EVA-HPMC greater than PLA-HPMC. No significant changes in body weight of mice after treatment were found in treated groups as compared to controlled groups. The preliminary results of our study suggest that needle device dosage form shows a controlled release behavior and may be applicable as a drug carrier for delivery of antitumor drug in cancer chemotherapy.

Animals↗

Mesencephalic hemorrhage--a report of 3 cases.

We studied three patients with spontaneous mesencephalic hemorrhages. All presented with some degree of impaired consciousness and abnormal ocular movements. One patient had a convergence-retraction nystagmus with a unilateral hemorrhage confined to the dorsal midbrain. Another patient showed left third nerve palsy due to a unilateral hemorrhage that involved ventral midbrain. The third patient revealed left internuclear ophthalmoplegia with ataxia due to a pinpoint hemorrhage in the tegmentum of the left midbrain. The patients survived and major neurologic deficits recovered, but abnormal ocular movements persisted.

Adult↗

Human IgE and IgG antibodies to mosquito proteins detected by the immunoblot technique.

Immunoblot technique was used in this study to detect IgE and IgG antibodies in human sera against mosquito antigens. Mosquito proteins were separated on SDS-polyacrylamide gels and transferred electrophoretically to nitrocellulose papers. After incubation with sera from different individuals, the precipitated bands were analyzed with enzyme-labeled goat anti-human immunoglobulins. Distinct patterns of antigen were recognized by IgE and IgG antibodies.

Adolescent↗

[Using anti-sera and monoclonal antibodies against Aspergillus fumigatus to study its cross-reactions with Alternaria alteria and Penicillium sp].

Using rabbit polyclonal and mouse monoclonal antibodies against Aspergillus fumigatus, we analyzed their cross-reaction with Alternaria alteria and Penicillium sp. by enzyme immuno assay (EIA) and radioimmunoprecipitation (RIP). It was found that neither of these two categories of antibodies reacted with Alternaria alteria while both reacted with Penicillium sp.. When components from Penicillium sp. precipitated by rabbit antisera were analyzed on 10% SDS-polyacrylamide gel electrophoresis (SDS-PAGE), a wide range of bands with molecular weights larger than 90 K and a single 70 K band were observed. No band was found after the rabbit antisera was adsorbed with Aspergillus fumigatus. Moreover, two monoclonal antibodies against Aspergillus fumigatus cross-reacted with high molecular weight (greater than 200K) components of Penicillium sp.. These results suggest that the antigen of Alternaria alteria is different from that of Aspergillus fumigatus, and that Penicillium sp. and Aspergillus fumigatus share some antigenic components. In another experiment, human allergic sera containing IgE antibodies to Aspergillus fumigatus were tested against Penicillium sp. by RIP. No cross-reaction was observed. This suggests that in spite of sharing common antigenic components between these two fungi, the allergenic components of Aspergillus fumigatus is different from those of Penicillium sp..

Alternaria↗

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↗