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Biomedical subjects

J Cheong

Publications and source records attributed to J Cheong.

30 records · Page 2Linked to original sources

Effects of sensation seeking, instruction set, and alcohol/placebo administration on aggressive behavior.

Sixty-three male college students were assessed on the number of aversive sound blasts they administered in response to their fictitious task partner's blasts in a variation of the Taylor aggression paradigm. Subjects were randomly assigned to one of three alcohol dosing conditions (placebo, placebo/expect alcohol, and alcohol) and one of three instruction conditions (aggression-told the noise blasts were meant to disrupt task performance; altruism-told the noise blasts were meant to improve concentration; ambiguous-either aggression or altruism). A significant three-way interaction of dosing condition by instruction by subjects' sensation seeking was found, such that high sensation seekers in the alcohol condition, compared to low sensation seekers, delivered more noise blasts in the aggression instruction condition, whereas they administered fewer blasts in the altruism condition. High sensation seekers in the placebo condition yielded an opposite pattern of results. The results were interpreted in terms of the effects of "alcohol myopia" on the disinhibition of socially disapproved behaviors and in terms of the moderating effects of personality and situational factors.

Adult↗

MDCK (Madin-Darby canine kidney) cells: A tool for membrane permeability screening.

The goal of this work was to investigate the use of MDCK (Madin-Darby canine kidney) cells as a possible tool for assessing the membrane permeability properties of early drug discovery compounds. Apparent permeability (Papp) values of 55 compounds with known human absorption values were determined using MDCK cell monolayers. For comparison, Papp values of the same compounds were also determined using Caco-2 cells, a well-characterized in vitro model of intestinal drug absorption. Monolayers were grown on 0. 4-microm Transwell-COL membrane culture inserts. MDCK cells were seeded at high density and cultured for 3 days, and Caco-2 cells were cultured under standard conditions for 21 to 25 days. Compounds were tested using 100 microM donor solutions in transport medium (pH 7.4) containing 1% DMSO. The Papp values in MDCK cells correlated well with those in Caco-2 cells (r2 = 0.79). Spearman's rank correlation coefficient for MDCK Papp and human absorption was 0.58 compared with 0.54 for Caco-2 Papp and human absorption. These results indicate that MDCK cells may be a useful tool for rapid membrane permeability screening.

Algorithms↗

Activating transcription factor-2 regulates phosphoenolpyruvate carboxykinase transcription through a stress-inducible mitogen-activated protein kinase pathway.

Several protein-nucleic acid complexes are observed when nuclear extracts from hepatoma cells are assayed for binding to the cAMP response element found in the phosphoenolpyruvate carboxykinase-cytosolic (PEPCK-C) promoter. Although cAMP response element-binding protein and CCAAT/enhancer binding proteins alpha and beta have been identified as liver factors that bind this motif, an uncharacterized, slower migrating complex was also observed. We identify activating transcription factor-2 (ATF-2) as the factor in this complex and show that ATF-2 stimulates expression from the PEPCK-C promoter. ATF-2 is a basic-leucine zipper transcription factor and a target for stress-activated protein kinases. We demonstrate that p38beta mitogen-activated protein (MAP) kinase augments ATF-2 transactivation activity on the PEPCK-C promoter, which is consistent with the interpretation that PEPCK-C promoter activity is maintained under stress through a p38 MAP kinase dependent pathway. In this regard, we show that treatment with sodium arsenite, a known activator of p38 MAP kinases, also stimulates expression from the PEPCK promoter. These results show that ATF-2 can stimulate transcription of the PEPCK-C promoter and support a role for stress inducible kinases in the maintenance of PEPCK-C expression.

Activating Transcription Factor 2↗

Effect of religion and religiosity on alcohol use in a college student sample.

Two hundred and sixty-three alcohol using college students completed a questionnaire on their levels of alcohol use, problems with alcohol use, reasons for drinking, perceptions of control over drinking, impulsivity, venturesomeness, irrational beliefs, neuroticism, expectations of alcohol effects, depression, social norms, religious affiliation and intrinsic and extrinsic religiosity. Analyses of variance revealed that students with no religious affiliation reported significantly higher levels of drinking frequency and quantity, getting drunk, celebratory reasons for drinking and perceived drinking norms than those of either Catholic or Protestant religious affiliation, while no significant differences across groups were found for alcohol use problems. Protestants reported significantly higher levels of perceived drinking control than Catholics. Intrinsic religiosity, reflecting one's ego involvement with the tenets of one's religion, appeared to play a more important positive role over drinking behavior for Protestants than for Catholics.

Adult↗

ATF-2 and C/EBPalpha can form a heterodimeric DNA binding complex in vitro. Functional implications for transcriptional regulation.

We screened an expression cDNA library with a radiolabeled C/EBPalpha fusion protein and isolated three independent cDNAs encoding ATF-2, a bZIP protein that binds cAMP response elements (CRE). This interaction requires the respective bZIP domains, which form a typical bZIP heterodimer with altered DNA binding selectivity. C/EBPalpha and ATF-2 homodimers bind CRE sites, but ATF-2:C/EBPalpha heterodimers do not. Heterodimers bind an asymmetric sequence composed of one consensus half-site for each monomer, and may thus have a unique regulatory function. As predicted, co-transfection of ATF-2 with C/EBPalpha results in decreased activation of transcription driven from consensus C/EBP-binding sites. In contrast, C/EBPalpha and ATF-2 function cooperatively to activate transcription driven by the asymmetric sequence. Both factors are expressed in liver, where immunoprecipitation experiments show that ATF-2 co-precipitates with C/EBPalpha. These results are consistent with the interpretation that C/EBPalpha and ATF-2 can associate in vivo. Moreover, the formation of ATF-2:C/EBPbeta heterodimers suggests that cross-family dimerization with ATF-2 may be a general property for C/EBP family proteins.

Activating Transcription Factor 2↗

Hepatitis B virus X protein is a transcriptional modulator that communicates with transcription factor IIB and the RNA polymerase II subunit 5.

Hepatitis B virus X protein (HBx) transactivates viral and cellular genes through a wide variety of cis-elements. However, the mechanism is still obscure. Our finding that HBx directly interacts with RNA polymerase II subunit 5 (RPB5), a common subunit of RNA polymerases, implies that HBx directly modulates the function of RNA polymerase (Cheong, J. H., Yi, M., Lin, Y., and Murakami, S. (1995) EMBO J. 14, 142-150). In this context, we examined the possibility that HBx and RPB5 interact with other general transcription factors. HBx and RPB5 specifically bound to transcription factor IIB (TFIIB) in vitro, both of which were detected by either far-Western blotting or the glutathione S-transferase-resin pull-down assay. Delineation of the binding regions of these three proteins revealed that HBx, RPB5, and TFIIB each has two binding regions for the other two proteins. Co-immunoprecipitation using HepG2 cell lysates that express HBx demonstrated trimeric interaction in vivo. Some HBx substitution mutants, which had severely impaired transacting activity, exhibited reduced binding affinity with either TFIIB or RPB5 in a mutually exclusive manner, suggesting that HBx transactivation requires the interactions of both RPB5 and TFIIB. These results indicated that HBx is a novel virus modulator that facilitates transcriptional initiation by stabilizing the association between RNA polymerase and TFIIB through communication with RPB5 and TFIIB.

Gene Expression Regulation, Viral↗

Transactivation of human hepatitis B virus X protein, HBx, operates through a mechanism distinct from protein kinase C and okadaic acid activation pathways.

Human hepatitis B virus (HBV) X protein, HBx, transactivates virus and host genes through a wide variety of cis-elements. Expression of HBx is controlled by HBV enhancer 1 (Enh1). Both Enh1 and the core sequence of Enh1, which consists of an AP-1 related site (cFAP1) and a C stretch, respond to HBx and a phorbol ester (TPA). Biochemical pathways of the responses to HBx and TPA are still controversial. We therefore asked whether HBx and TPA stimulate Enh1 core activity through a common process. Protein kinase C (PKC) inhibitors, H-7 and staurosporin, did not inhibit HBx transactivation at concentrations sufficient to abolish the TPA effects in HepG2 cells. Although HBx transactivation synergized independently with TPA or a phosphoprotein phosphatase inhibitor, okadaic acid (OA), the PKC inhibitors eliminated only the TPA contribution. HBx transactivation required both the cFAP1 and the C stretch of the Enh1 core region; however, mutations in either or both of the two cis-elements demonstrated that TPA augmentation required only cFAP1. These results imply that HBx transactivation operates through a mechanism distinct from the PKC and OA activation pathways.

Base Sequence↗

Detection of the putative E2 protein of hepatitis C virus in human liver.

The question was asked whether a predicted envelope protein, considered to be processed from the polyprotein precursor encoded by the putative E2/NS1 region of the hepatitis C virus (HCV) genome, may be observed in HCV-infected humans. Two polyclonal antibodies against recombinant E2/NS1 proteins were prepared and their reactivity tested against liver extracts from HCV-infected patients by immunoblotting analysis. A band corresponding to a size of 44 kDa was detected in liver extracts from patients who were positive for the HCV-specific antibody anti-C100-3 but not in liver extracts from patients who did not have anti-C100-3 antibody. Additionally, no band was detected using preimmune sera or antisera which had been preabsorbed with recombinant E2/NS1 proteins. Deglycosylation studies demonstrated that the 44 kDa protein was a glycosylated form of a 38 kDa protein which corresponds to the predicted molecular weight of the putative E2/NS1 protein. These results suggest that the 44 kDa protein is a product of the E2/NS1 region. Frequent observation of the 44 kDa band in cases of chronic active hepatitis C suggests a correlation between the expression of this protein and the progression of hepatitis.

Adult↗

The use of animals in medical education: a question of necessity vs. desirability.

An issue in current animal welfare ethics is the use of animals in medical education. At stake is the conflict of pain and suffering of the animals vs. the benefit to the students. The educator's role is to balance these two concepts. If the animals do suffer, this has to be justified by clearly establishing the necessity of their use. Neither this justification nor the methods for making the decision are clear. Addressed in this discussion are the arguments for and against animal use, alternatives, and proposals for the resolution of the controversy.

Animal Experimentation↗

Safety of postabortion sterilisation compared with interval sterilisation. A controlled study.

406 women--about one-fifth of those requesting an induced abortion and sterilisation over a thirty-three-month period--volunteered to be allocated randomly to either a concurrent induced-abortion/sterilisation group or a group which was sterilised six weeks after abortion. The abortion-attributable and sterilisation-attributable complication rates of 3.8% and 5.2%, respectively, for the concurrent group did not differ significantly from the 6.7% and 6.9% rates for the interval group. The estimated 2%-10% of women who would have changed their minds must be set against the 4% of women who became pregnant again before being sterilised. Efforts should be made to identify women likely to regret sterilisation.

Abortion, Induced↗

Psychological sequelae of sterilization in women in Singapore.

The Chinese in Singapore erroneously believe that there is an association between sterilization and castration. This belief has led to deep-seated fears that sterilization may result in obesity, physical weakness, and impairment of sexual function. Beginning in 1969, Singapore authorities introduced increasingly stronger social policies to help reduce family size. Subsequently, there was a large increase in the number of tubal ligations. It was initially thought that this might result in a high incidence of psychological sequelae. A study of 150 women who had had culdoscopic ligations showed that 6.3 percent were dissatisfied at the end of 2 years. Women with fewer than 4 children and those with fewer than 2 sons tended to be more dissatisfied with sterilization.

Adult↗