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Biomedical subjects

C Chang

Publications and source records attributed to C Chang.

At least 379 records · Page 21Linked to original sources

Identification of a new member of the steroid receptor super-family by cloning and sequence analysis.

We have isolated a human testis complementary DNA clone on the basis of homology to the DNA binding domain of steroid receptors. Expression of this complementary DNA, which we call TR2, produces a 52 kd DNA binding protein that does not bind significantly to any known steroids. Northern blot analysis has shown that TR2 mRNA is about 2.5 kilobases (kb) and is relatively abundant in androgen-sensitive organs, such as ventral prostate and seminal vesicle. Dot blot hybridization indicates that TR2 mRNA levels increased after castration of rats, and this increase is reversed by 5 alpha-dihydrotestosterone injection. This evidence suggests that TR2 mRNA levels are negatively controlled by androgen in the rat ventral prostate.

Amino Acid Sequence↗

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↗

Anti-interleukin-2 receptor monoclonal antibody therapy induces anti-idiotypic antibodies in mice that block both in vitro and in vivo activity.

Monoclonal antibodies (Mab) targeting certain T cell-surface proteins including the interleukin-2 (IL2) receptor molecule exert powerful immunosuppressive effects. A potential limiting factor to Mab therapy is the formation of neutralizing anti-idiotypic antibodies (Anti-Id). In this study, we demonstrate that an anti-IL2 receptor Mab, M7/20, when administered at doses which are immunosuppressive in vivo rapidly elicits an anti-idiotypic (anti-Id) antibody response. The induced antibodies are capable of blocking M7/20 binding to its target, the IL2 receptor, in vitro. Such anti-Id when given in concert with M7/20 block the expected in vivo inhibitory effects in delayed type hypersensitivity. Thus, mice respond to therapeutic doses of Mab therapy with the formation of neutralizing anti-Id. As this response is similar to that observed in humans given xenogeneic Mab, this model may be useful to further our understanding of this form of therapy.

Animals↗

Restriction fragment length polymorphism linkage map for Arabidopsis thaliana.

We have constructed a restriction fragment length polymorphism linkage map for the nuclear genome of the flowering plant Arabidopsis thaliana. The map, containing 90 randomly distributed molecular markers, is physically very dense; greater than 50% of the genome is within 1.9 centimorgans, or approximately 270 kilobase pairs, of the mapped DNA fragments. The map was based on the meiotic segregation of markers in two different crosses. The restriction fragment length polymorphism linkage groups were integrated with the five classically mapped linkage groups by virtue of mapped mutations included in these crosses. Markers consist of both cloned Arabidopsis genes and random low-copy-number genomic DNA clones that are able to detect polymorphisms with the restriction enzymes EcoRI, Bgl II, and/or Xba I. These cloned markers can serve as starting points for chromosome walking, allowing for the isolation of Arabidopsis genes of known map location. The restriction fragment length polymorphism map also can associate clones of unknown gene function with mutant phenotypes, and vice versa.

Bacterial Proteins↗

Air embolism and the radial arterial line.

A clinical case of apparent air embolism through a radial artery line served as the impetus to conduct a study in primates to investigate the possibility of air embolism from the radial artery into the cerebral circulation. Using 133Xe cerebral scanning, we demonstrated that greater than 2 ml of air in the radial artery would result in retrograde passage of air into the vertebral system and then into the brain.

Animals↗

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↗

Androgen repression of the production of a 29-kilodalton protein and its mRNA in the rat ventral prostate.

The regression of the ventral prostate, after a rat is deprived of androgens by castration, is accompanied by a marked decrease in the prostate's ability to synthesize RNA and major proteins. Surprisingly, in vitro translation of prostate RNA, isolated from rats 2 days after castration, detects four proteins with Mr of approximately 29,000, 37,000, 46,000, and 49,000 whose message levels increased 4- to 12-fold compared to results from normal rats. According to cDNA dot hybridization analysis, the increase after castration in the level of the 29-kDa protein-mRNA (per unit amount of DNA) was reversed within 6 h by androgen treatment of castrated rats. In contrast, the level of a mRNA in male rat liver, which hybridized to a cloned probe for the prostate 29-kDa protein-mRNA was reduced by castration and increased by androgen treatment. During an in vitro incubation, the ventral prostates of normal rats were much less efficient than the prostates of rats castrated 2 days earlier in synthesizing a 29-kDa protein. Despite the fact that androgenic manipulation of rats induced very rapid and significant changes in the production of the 29-kDa protein and in the level of its mRNA, the cellular level of this protein in the prostate, as determined by radioimmunoassay, was maintained at near normal values throughout the 2-week experimental period. Thus, the prostate appears to have a mechanism, based on androgen repression of certain genes, to maintain the cellular levels of the 29-kDa protein and possibly other structurally or functionally important proteins during both the periods of androgen-dependent growth and the castration-induced regression. The loss of such a regulatory mechanism may result in androgen-independent abnormal prostate growth.

Androgens↗

Hyperfractionated photon radiation therapy in the treatment of advanced squamous cell carcinoma of the oral cavity, pharynx, larynx, and sinuses, using radiation therapy as the only planned modality: (preliminary report) by the Radiation Therapy Oncology Group (RTOG).

From August 1979 to June 1983, the RTOG conducted a prospective Phase III study that compared a standard schedule with five fractions per week of 180 to 200 cGy per day to a total dose of 6600-7380 cGy, with a hyperfractionation regimen consisting of two fractions of 120 cGy per day, separated by a rest period of 3 to 6 hours for a total of 6000 cGy. A total of 210 patients were entered, of which 187 are analyzed. Complete initial tumor clearance in the head and neck was achieved by radiotherapy in 61% of the patients assigned to the standard schedules and in 59% of those assigned to the continuous hyperfractionation schedule; surgical salvage contributed towards achieving complete response in 5% and 7% of patients, respectively. The Kaplan-Meier estimates for loco-regional control of tumor at 1 and 2 years was 39% and 29% for the standard schedules, and 43% and 30% for the hyperfractionation schedule. The endpoints examined to evaluate therapeutic effects do not indicate that the stated hyperfractionation schedule is different than the standard RTOG treatment schedule for head and neck cancer. Acute normal tissue reactions appear to be more severe with the hyperfractionation schedule but the incidence of late reactions is similar in both groups. There is a tendency toward more severe acute reactions when the interval between the two fractions per day is 4.5 hrs or less in comparison to intervals longer than 4.5 hrs.

Aged↗

Epidemiological characteristics of twinning rates in Taiwan.

Delivery records of public hospitals and birth certificates of household registration offices were examined to study the epidemiological characteristics of twinning rate from 1955 to 1984 in Taiwan. The MZ twinning rate was consistently higher than the DZ rate during the study period. The DZ rate declined steadily from 2.7 per 1000 in 1955 to 1.3 per 1000 in 1975, and then gradually increased to 3.6 per 1000 in 1984. The MZ rate peaked periodically in 1956, 1966 and 1976, and gradually increased from 3.3 per 1000 in 1978 to 5.9 per 1000 in 1986. Both MZ and DZ rates were higher in urban than in rural areas and they were also higher in northern Taiwan than elsewhere in the island. While both MZ and DZ rates increased with maternal age and parity, the maternal age difference and the parity difference were more striking in DZ than in MZ rates. The international comparison also showed a greater racial difference in maternal age-specific DZ than MZ twinning rates; and the older the maternal age, the greater the international discrepancy in DZ rates.

Birth Rate↗

Expression of the precore region of an avian hepatitis B virus is not required for viral replication.

The core-antigen-coding region of all hepadnaviruses is preceded by a short, in-phase open reading frame termed precore whose expression can give rise to core-antigen-related polypeptides. To explore the functional significance of precore expression in vivo, we introduced a frameshift mutation into this region of the duck hepatitis B virus (DHBV) genome and examined the phenotype of this mutant DNA by intrahepatic inoculation into newborn ducklings. Animals receiving mutant DNA developed DHBV infection, as judged by the presence in hepatocytes of characteristic viral replicative intermediates; molecular cloning and DNA sequencing confirmed that the original mutation was present in the progeny genomes. Infection could be efficiently transmitted to susceptible ducklings by percutaneous inoculation with serum from mutant-infected animals, indicating that infectious progeny virus was generated. These findings indicate that expression of the precore region of DHBV is not essential for genomic replication, core particle morphogenesis, or intrahepatic viral spread.

Animals↗

A study of occupational achievement of migrants to Kaohsiung City, Taiwan.

"Based on a survey of 452 migrants who moved into Kaohsiung City, Taiwan, in 1977, this paper tests two major hypotheses of occupational achievement within the context of migration. They are status attainment and information hypotheses. Using the Blau-Duncan basic model...[the author finds that] educational attainment of migrants is the most important factor in determining an individual's occupational achievement. More importantly, assistance from relatives has a negative effect on occupational achievement for rural migrants only." (SUMMARY IN CHI)

Asia↗

Derepression of HPRT locus on inactive X chromosome of human lymphoblastoid cell line.

Human XX lymphoblastoid cells with a deletion in the HPRT locus on the active X were exposed to HPRT clone pHPT32. HPRT+ isolates GPT3 and GPT5 lacked pHPT32 DNA, suggesting that their HPRT+ phenotype resulted from expression of a cellular gene. GPT3 mutated to thioguanine resistance at least 100 times more frequently than cells in which the expressed HPRT locus was on the active X. Most GPT3-derived HPRT- had lost one entire X chromosome, indicating that the HPRT+ phenotype of GPT3 resulted from derepression of the HPRT locus on its inactive X. Virtually unchanged G6PD and PGK activities and the presence of a late-replicating X in GPT3 suggest that derepression of the inactive X was not general. Eleven of the GPT3-derived mutants had a tiny centric remnant that may result from a frequently operative mechanism of X chromosome loss. The detection of partial or complete loss of an X by direct selection presents unusual opportunities for genotoxicity detection with human cells.

Cell Line↗

Molecular cloning and DNA sequence of the Arabidopsis thaliana alcohol dehydrogenase gene.

Arabidopsis thaliana provides an excellent experimental plant system for molecular genetics because of its remarkably small genome size, near absence of dispersed middle repetitive DNA, and short life cycle. We have cloned and determined the nucleotide sequence of a single-copy gene from A. thaliana likely to be the gene encoding alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1). The gene was isolated from a random recombinant library by cross-hybridization with a maize Adh1 gene probe. The DNA sequence contains an open reading frame capable of encoding a polypeptide the same length as maize ADH1 and ADH2 (379 amino acids) and having approximately equal to 80% homology with both maize enzymes. This open reading frame is interrupted by six introns whose positions are conserved with six of the nine intron positions present in both maize genes. The 5' and 3' untranslated regions are, respectively, 58 and 204 base pairs long. Sequences important for eukaryotic gene expression such as the TATA box, polyadenylylation signal, and intron splicesite sequences are found in the expected locations. The gene hybridizes to a specific anaerobically induced RNA in Arabidopsis whose appearance correlates with the anaerobic induction of Arabidopsis ADH protein.

Alcohol Dehydrogenase↗

Further studies on the biosynthesis of chlorothricin.

Feeding experiments with [U-13C3]- and (2R)-[1-2H2]glycerol showed that glycerol is incorporated intact into carbon atoms 22, 23 and 24 of the aglycone of chlorothricin. C-1 of glycerol gives rise to C-22 with retention of one atom of deuterium, which occupies the H-22R position. A mechanism for the assembly of the aglycone is proposed which invokes phosphoenolpyruvate as the direct precursor of the 3-carbon moiety and a Baeyer-Villiger oxidation as the mode of formation of the macrocyclic lactone functionality. A feeding experiment with [1,2-13C2]succinate suggests that the propionate units of the aglycone polyketide are formed entirely via the methylmalonyl-CoA mutase reaction. The formation of the two 2,6-dideoxy-D-rhamnose moieties of chlorothricin from glucose was shown to involve replacement of the 2-hydroxyl group of the sugar by hydrogen with inversion of configuration at C-2. This contrasts with the retention stereochemistry observed earlier for the analogous formation of the 2,6-dideoxyhexose moiety of the antibiotic granaticin.

Aminoglycosides↗

A highly sensitive immunoenzymometric assay involving "common-capture" particles and membrane filtration.

This highly sensitive immunoenzymometric method involves monoclonal antibodies, a common-capture microsphere, and a rapid, membrane-filtration separation step. The common-capture solid phase is monoclonal anti-fluorescein antibody convalently attached to 6.5 micron-diameter latex particles. In sandwich-type assays for large-molecule analytes, the capture antibody is conjugated with fluorescein isothiocyanate and the probe antibody is conjugated with beta-galactosidase (EC 3.2.1.23). In competitive assays for small analytes, the analyte-beta-galactosidase conjugate competes with the analyte in the clinical samples for the fluoresceinated capture antibody. After simultaneous incubation of the reagents for 2 h, the bound and unbound reagents are separated by filtration through the bottom of each well of a 96-well plate. Substrate (4-methylumbelliferyl-beta-D-galactopyranoside) is then added to the wells, and the rate of product formation is determined kinetically for 12 min. The rate is proportional to the concentration of analyte in the sandwich assays and inversely proportional in the competitive assays. The assay results for choriogonadotropin, thyrotropin, digoxin, and thyroxin show the assay to be sensitive, rapid, and applicable to any size analyte. With this system, several different sandwich and (or) competitive-type assays can be performed simultaneously on the same plate.

Antibodies, Monoclonal↗