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Biomedical subjects

J Cheong

Publications and source records attributed to J Cheong.

At least 19 recordsLinked to original sources

A QTL located on chromosome 4A associated with dormancy in white- and red-grained wheats of diverse origin.

Improved resistance to preharvest sprouting in modern bread wheat (Triticum aestivum. L.) can be achieved via the introgression of grain dormancy and would reduce both the incidence and severity of damage due to unfavourable weather at harvest. The dormancy phenotype is strongly influenced by environmental factors making selection difficult and time consuming and this trait an obvious candidate for marker assisted selection. A highly significant Quantitative Trait Locus (QTL) associated with grain dormancy and located on chromosome 4A was identified in three bread wheat genotypes, two white- and one red-grained, of diverse origin. Flanking SSR markers on either side of the putative dormancy gene were identified and validated in an additional population involving one of the dormant genotypes. Genotypes containing the 4A QTL varied in dormancy phenotype from dormant to intermediate dormant. Based on a comparison between dormant red- and white-grained genotypes, together with a white-grained mutant derived from the red-grained genotype, it is concluded that the 4A QTL is a critical component of dormancy; associated with at least an intermediate dormancy on its own and a dormant phenotype when combined with the R gene in the red-grained genotype and as yet unidentified gene(s) in the white-grained genotypes. These additional genes appeared to be different in AUS1408 and SW95-50213.

Australia↗

Brain lactic alkalosis in Aicardi-Goutières syndrome.

Aicardi-Goutières syndrome is a rare progressive encephalopathy characterized by acquired microcephaly, basal ganglia calcification, and chronic CSF lymphocytosis, raised levels of interferon alpha in CSF and plasma and chill-blain type lesions. A possible mechanism of injury is cytokine related microangiopathy. We report brain imaging and proton (1H) and phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) findings during the first year after birth in two patients. In patient 1 the evolution of brain metabolite ratios and intracellular pH obtained from serial 1H (long TE) and 31P MRS studies are described; in patient 2 a single 1H (short TE) MRS study is described. Imaging findings included basal ganglia calcifications, cerebral atrophy, and leukodystrophy. The MRS results demonstrated that Aicardi-Goutières syndrome is associated with reduced NAA/Cr, reflecting decreased neuronal/axonal density or viability, increased myo-inositol/Cr, reflecting gliosis or osmotic stress and a persisting brain lactic alkalosis. A brain lactic alkalosis has also been observed in those infants surviving perinatal hypoxia-ischaemia but with a poor neurodevelopmental outcome. A possible mechanism leading to brain alkalosis is up-regulation of the Na+/H+ transporter by focal areas of ischaemia related to the microangiopathy or by pro-inflammatory cytokines. Such brain alkalosis may be detrimental to cell survival and may increase glycolytic rate in astrocytes leading to an increased production of lactate.

Alkalosis↗

Lipopolysaccharide prevents cell death caused by glutathione depletion: possible mechanisms of protection.

Glutathione is an important cellular antioxidant present at high concentrations in the brain. We have previously demonstrated that depletion of glutathione in mesencephalic cultures results in cell death and that the presence of glia is necessary for the expression of toxicity. Cell death following glutathione depletion can be prevented by inhibition of lipoxygenase activity, implicating arachidonic acid metabolism in the toxic events. In this study we examined the effect of glial activation, known to cause secretion of cytokines and release of arachidonic acid, on the toxicity induced by glutathione depletion. Our data show that treatment with the endotoxin lipopolysaccharide activated glial cells in mesencephalic cultures, increased interleukin-1beta in microglia and caused depletion of glutathione. The overall effect of lipopolysaccharide treatment, however, was protection from damage caused by glutathione depletion. Addition of cytokines or growth factors, normally secreted by activated glia, did not modify L-buthionine sulfoximine toxicity, although basic fibroblast growth factor provided some protection. A large increase in the protein content and the activity of Mn-superoxide dismutase, observed after lipopolysaccharide treatment, may indicate a role for this mitochondrial antioxidant enzyme in the protective effect of lipopolysaccharide. This was supported by the suppression of toxicity by exogenous superoxide dismutase. Our data suggest that superoxide contributes to the damage caused by glutathione depletion and that up-regulation of superoxide dismutase may offer protection in neurodegenerative diseases associated with glutathione depletion and oxidative stress.

Animals↗

Usefulness of silicone plate for sellar floor reconstruction.

During the transsphenoidal approach (TSA), the proper sellar floor reconstruction plays an important role in the surgical results. The authors have evaluated the usefulness of a silicone as a substitute for bone splint in sellar floor reconstruction. Silicone plates were used in 10 patients who had 7 pituitary adenomas, 2 Rathke's cleft cysts, and 1 metastatic tumor. Among the ten cases, seven underwent standard TSAs and three received extended TSAs. The silicone plate was cut to a size slightly larger than that of bone window, inserted with a three-pronged fork, and then adjusted precisely. In nine patients, complications that related to surgical repair did not occur. A postoperative cerebrospinal fluid (CSF) rhinorrhea occurred in one pituitary macroadenoma, and no infection was observed in any case. From the authors' experience, advantages of the silicone plate are its simplicity to shape for any size of defects, and the easy detectability of the previous bone window at reoperation.

Adult↗

Functional interaction of bZIP proteins and the large subunit of replication factor C in liver and adipose cells.

The transcription factor CCAAT/enhancer-binding protein-alpha (C/EBPalpha) has a vital role in cell growth and differentiation. To delineate further a mechanism for C/EBPalpha-mediated differentiation, we screened C/EBPalpha-interacting proteins through far-Western screening. One of the strongest interactions was with RFC140, the large subunit of the replication factor C complex. C/EBPalpha specifically interacted with RFC140 from rat liver nuclear extract as determined by a combination of affinity chromatography and co-immunoprecipitation. Subsequent far-Western blotting showed that the bZIP domain of C/EBPalpha interacted with the DNA-binding region of RFC140. Overexpression of RFC140 in mammalian cells increased the transactivation activity of C/EBPalpha on both minimal and native promoters. Consistent with the enhanced transactivation, a complex of C/EBPalpha and RFC140 proteins with the cognate DNA element was detected in vitro. The specific interaction between C/EBPalpha and RFC140 was detected in the terminal differentiation of 3T3-L1 preadipocytes to adipocytes. The synergistic transcription effect of these two proteins increased the promoter activity and protein expression of peroxisome proliferator-activated receptor-gamma, which is a main regulator of adipocyte differentiation. Our results demonstrate that the specific transcription factor C/EBPalpha and the general DNA replication factor RFC140 interact functionally and physically. This observation highlights a unique mechanism by which the levels of the general replication factor can strongly modulate the functional activity of the specific transcription factor as a coactivator.

Adipocytes↗

Functional interaction of transcriptional coactivator ASC-2 and C/EBPalpha in granulocyte differentiation of HL-60 promyelocytic cell.

HL-60 promyelocytic cells were treated with retinoic acid (RA) to stimulate granulocyte differentiation. CCAAT/enhancer binding protein alpha (C/EBPalpha) is known to be the molecular switch during early hematopoietic developmental events that direct cells to the granulocytic pathway. Here we show that the coactivator activating signal cointegrator-2 (ASC-2) plays an important role in differentiation of HL-60 cells into granulocytes by mediating C/EBPalpha-induced gene transcription. The differentiation inducer RA increased mRNA and protein expression of ASC-2. The protein-protein interaction of C/EBPalpha and ASC-2 was detected by coimmunoprecipitation during granulocyte differentiation. Subsequently, GST-pull-down assay revealed that the N-terminal transactivation domain of C/EBPalpha could interact with ASC-2. This functional interaction of ASC-2 with C/EBPalpha drove a synergistic enhancement of C/EBPalpha-dependent transactivation and overexpression of the N-terminal C/EBPalpha protein in HL-60 cells inhibited ASC-2 responsiveness for C/EBPalpha activity in granulocyte differentiation, indicating C/EBPalpha dependency of ASC-2 activity. Taken together, these results suggest that the differentiation-dependent expressed ASC-2 protein physically and functionally interacts with C/EBPalpha and increases its transactivation activity, regulating specific gene transcription for granulocyte differentiation.

CCAAT-Enhancer-Binding Protein-alpha↗

Ca2+/calmodulin-dependent protein kinase IV stimulates nuclear factor-kappa B transactivation via phosphorylation of the p65 subunit.

Calmodulin-dependent protein kinase IV (CaMKIV) is a key mediator of Ca(2+)-induced gene expression. In this study, CaMKIV was found to directly associate with and phosphorylate the nuclear factor-kappaB (NFkappaB) component p65 both in vitro and in vivo. The phosphorylation of p65 by CaMKIV resulted in recruitment of transcription coactivator cAMP-response element-binding protein-binding protein and concomitant release of corepressor silencing mediator for retinoid and thyroid hormone receptors, as demonstrated by the glutathione S-transferase pull down and mammalian two hybrid assays. In addition, cotransfection of CaMKIV resulted in cytosolic translocation of the silencing mediator for retinoid and thyroid hormone receptors. Consistent with these results, cotransfected CaMKIV dramatically stimulated the NFkappaB transactivation in mammalian cells. From these results, NFkappaB is suggested to be a novel downstream effector molecule of CaMKIV.

Animals↗

Regulation of activating transcription factor-2 in early stage of the adipocyte differentiation program.

p38beta mitogen-activated protein kinase activity is required for the differentiation of 3T3-L1 fibroblasts into adipocytes. Activating transcription factor-2 (ATF-2) is efficiently phosphorylated and activated by p38beta kinase. These findings led us to examine a regulatory role of ATF-2 in adipocyte differentiation. The induction of ATF-2 protein precedes the expression of the transcription factors, peroxisome proliferator-activated receptor (PPAR) gamma and CCAAT/enhancer-binding protein (C/EBP) alpha. Consistent with early activation of p38beta kinase, the phosphorylation of ATF-2 was also detected in early stage of adipocyte differentiation. ATF-2 regulated gene transcription of PPARgamma, which was synergistically enhanced by p38beta kinase and C/EBPbeta proteins expression. Ectopic expression of ATF-2 in 3T3-L1 cells induced the endogenous PPARgamma protein levels. These results suggest that ATF-2 plays a role in a primary regulator of adipocyte differentiation with C/EBPbeta through promoting adipogenesis-inducing transcription factors including PPARgamma and becomes associated earlier in the differentiation program as mitotic clonal expansion proceeds and the cells become initially differentiated.

Activating Transcription Factor 2↗

Mediating mechanisms in a program to reduce intentions to use anabolic steroids and improve exercise self-efficacy and dietary behavior.

This study investigated the mediating mechanisms responsible for the effects of a program designed to reduce intentions to use anabolic steroids, improve nutrition, and increase strength training self-efficacy. Fifteen of 31 high school football teams (N = 1,506 players at baseline) in Oregon and Washington were assigned to receive the intervention. The multicomponent program addressed the social influences promoting ergogenic drug use and engaging students in healthy nutrition and strength training alternative behaviors. Although the results differed across the three dependent variables, the program appeared to work by changing team norms. Unlike prevention of other drugs, changes in knowledge and perceived severity were mediators of program effects in this study.

Adolescent↗

Longitudinal relationship between the alcohol warning label and alcohol consumption.

OBJECTIVE: The present study reports the longitudinal relationship between alcohol warning label exposure and alcohol consumption among adolescents. METHOD: In-school surveys assessed adolescents at three annual time points beginning in tenth grade. There were 649 participants measured at all three time points; 51% were female. Four effects were the focus of the covariance structure, latent growth analysis of these data: (1) an exposure effect, whereby earlier alcohol use leads to more exposure to the warning label; (2) a deterrent effect, whereby earlier alcohol warning label exposure reduces subsequent alcohol consumption; (3) a harmful effect, corresponding to a positive relationship between early exposure and subsequent consumption; and (4) both exposure and deterrent effects operating at the same time. RESULTS: There was a statistically significant exposure effect such that earlier alcohol use was associated with later exposure to the warning. The association between earlier alcohol warning label exposure and subsequent alcohol use was generally negative but not statistically significant, suggesting that the warning did not affect alcohol consumption. CONCLUSIONS: These results suggest that the alcohol warning label is having the intended effect as described in the law requiring the warning. That is, it is informing and reminding persons of the risks associated with alcohol use. The warning does not appear to significantly increase or decrease alcohol consumption.

Adolescent↗

Effects of alcoholic beverage, instigation, and inhibition on expectancies of aggressive behavior.

To investigate the role of alcohol expectancy, situational factors, and personality variables in predicting postdrinking aggression, two questionnaire studies were conducted. Subjects were randomly assigned to imagine themselves and their responses in a scenario situation, which was a combination of different beverages (soda vs. alcohol), instigation, and inhibition conditions. Both studies found significant 3-way interactions of personality aggression proneness (Buss-Durkee Hostility Inventory Assault scale) by beverage condition and by situational cue condition on subjects' reported likelihood of engaging in aggressive behavior. Expected aggression was strongly associated with greater aggression proneness in the nonalcoholic condition when there was a situational cue (low inhibition in Study 1, high instigation in Study 2) invoking aggression, but not when the situational cue was absent. This relationship between aggression proneness and expected aggression, however, was attenuated in the alcoholic drink conditions in both studies. In general, it was found that the effect of alcohol on expected aggression was minor relative to the large and significant effects of aggression proneness, instigation, and inhibition.

Adolescent↗

A social learning perspective: a model of parenting styles, self-regulation, perceived drinking control, and alcohol use and problems.

BACKGROUND: This investigation sought to determine how different parenting styles are related to general self-regulatory processes that are linked to alcohol use and abuse. Self-regulation and, more specifically, thoughts of control over drinking are forms of positive self-control mechanisms. Parenting styles are known determinants of both negative and positive self-control mechanisms in offspring. According to social learning theory, stronger relationships between parenting style and self-regulatory processes would be expected from the parent who is the same sex as the respondent. METHODS: A total of 144 female and 107 male college students currently using alcohol were administered a questionnaire on their alcohol use and problems, perceived style of parenting (authoritarian, permissive, or authoritative) of their parents, self-regulation, and perceived control of drinking. A model linking parenting styles, self-regulatory processes, and control over drinking with alcohol use and alcohol problems was tested across sex groups by using structural equation modeling. RESULTS: In general, the parenting style of the parent of the same sex as the respondent's was found to be significantly related to self-regulation, which is known to be protective against alcohol use and abuse. A permissive parent of the same sex as the respondent was negatively associated with good self-regulatory processes for both men and women. Having an authoritative mother was also shown to be related to higher levels of self-regulation for women. CONCLUSIONS: Self-regulation mediated the pathway from a permissive parenting style to perceived drinking control, which, in turn, mediated the pathway from self-regulation to alcohol use and problems. Finally, self-regulation mediated the positive pathway from an authoritative mother to perceived control over drinking for women.

Adult↗

Direct binding of hepatitis B virus X protein and retinoid X receptor contributes to phosphoenolpyruvate carboxykinase gene transactivation.

The X gene product of the human hepatitis B virus (HBx), a major factor responsible for hepatitis and hepatocellular carcinoma, modulates transactivation by a variety of transcription factors. Herein, expression of the phosphoenolpyruvate carboxykinase (PEPCK) gene was found to be regulated transcriptionally by HBx through two distinct promoter regions. The cAMP response element (CRE)-1 site within the proximal promoter region mediated the HBx-induced transactivation of the PEPCK gene through C/EBP alpha and ATF-2. A retinoid X receptor (RXR) response element within the distal promoter region also contributed to the HBx-induced transactivation. Consistent with these results, HBx directly interacted with RXR, and the interaction interfaces were localized to the transactivation domain of HBx and the ligand binding domain of RXR.

Activating Transcription Factor 2↗

Increased expression of p53 and Bax in the spinal cords of rats with experimental autoimmune encephalomyelitis.

The expression of pro-apoptotic molecules p53 and Bax in the spinal cord of rats with experimental autoimmune encephalomyelitis (EAE) was examined. Apoptosis was confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method. TUNEL (+) apoptotic cells were mainly either ED1 (+) macrophages or T-cells in the parenchyma of EAE. Western blot analysis showed that both p53 and Bax expression significantly (P<0. 01) increased in the spinal cords of EAE rats at the peak stage, and thereafter declined. An immunohistochemical study showed that inflammatory cells (notably T cells) in the parenchyma express p53 and Bax, while brain cells, including neurons and glia, were devoid of nuclear staining for these molecules. The nuclear expression of p53 largely matches apoptotic cells in the parenchyma of EAE. These findings suggest that the pro-apoptotic molecules p53 and Bax may play an important role in eliminating T cells in the parenchyma in EAE.

Animals↗

Silencing mediator of retinoic acid and thyroid hormone receptors, as a novel transcriptional corepressor molecule of activating protein-1, nuclear factor-kappaB, and serum response factor.

Silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) is known to interact with Sin3 and recruit the histone deacetylases (HDACs) that lead to hypoacetylation of histones and transrepression of target transcription factors. Herein, we found that coexpression of SMRT significantly repressed transactivations by activating protein-1 (AP-1), nuclear factor-kappaB (NFkappaB), and serum response factor (SRF) in a dose-dependent manner, but not in the presence of trichostatin A, a specific inhibitor of HDAC. Similarly, coexpression of HDAC1 and mSin3A also showed repressive effects. Consistent with these results, the C-terminal region of SMRT directly interacted with SRF, the AP-1 components c-Jun and c-Fos, and the NFkappaB components p50 and p65, as demonstrated by the yeast and mammalian two hybrid tests as well as the glutathione S-transferase pull down assays. Thus, we concluded that SMRT serves to recruit Sin3/HDACs to SRF, NFkappaB, and AP-1 in vivo and modulate their transactivation.

Animals↗

The adolescents training and learning to avoid steroids program: preventing drug use and promoting health behaviors.

BACKGROUND: Use of alcohol and other illicit drugs by adolescent male athletes is a significant problem. Participation in sports may encourage use of drugs that enhance athletic performance, especially anabolic steroids (AS). Because, to our knowledge, no other intervention has successfully altered substance abuse by athletes, we developed and assessed the efficacy of a team-centered, sex-specific education program designed to reduce adolescent athletes' intentions to use and use of AS and alcohol and other illicit drugs. METHODS: We studied 31 high school football teams that comprised 3207 athletes in 3 successive annual cohorts (1994-1996). The intervention included interactive classroom and exercise training sessions given by peer educators and facilitated by coaches and strength trainers. Program content included discussion of sports nutrition, exercise alternatives to AS and sport supplements, and the effects of substance abuse in sports, drug refusal role-playing, and the creation of health promotion messages. Questionnaires assessing AS, the use of sport supplements and alcohol and other illicit drugs, and potential risk and protective factors were administered before and after the intervention (before and after the football season) and up to 1 year after the program. RESULTS: At season's end, intentions to use (P<.05) and actual AS use (P<.04) were significantly lower among students who participated in the study. Although AS reduction did not achieve significance at 1 year (P<.08), intentions to use AS remained lower (P = .02). Illicit drug use (marijuana, amphetamines, and narcotics) was reduced at 1 year, whether alcohol was included (P = .04) or excluded (P = .02) from the index. Other long-term effects included fewer students reporting drinking and driving (P = .004), less sport supplement use (P = .009), and improved nutrition behaviors (P<.02). CONCLUSIONS: Use of alcohol and other illicit drugs and associated harmful activities can be prevented with a sex-specific, team-centered education. School athletic teams provide an optimal environment in which to provide drug prevention and health promotion education.

Adolescent↗

Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2.

ASC-2 was recently discovered as a cancer-amplified transcription coactivator molecule of nuclear receptors, which interacts with multifunctional transcription integrators steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP)/p300. Herein, we report the identification of three mitogenic transcription factors as novel target molecules of ASC-2. First, the C-terminal transactivation domain of serum response factor (SRF) was identified among a series of ASC-2-interacting proteins from the yeast two-hybrid screening. Second, ASC-2 specifically interacted with the activating protein-1 (AP-1) components c-Jun and c-Fos as well as the nuclear factor-kappaB (NFkappaB) components p50 and p65, as demonstrated by the glutathione S-transferase pull-down assays as well as the yeast two-hybrid tests. In cotransfection of mammalian cells, ASC-2 potentiated transactivations by SRF, AP-1, and NFkappaB in a dose-dependent manner, either alone or in conjunction with SRC-1 and p300. In addition, ASC-2 efficiently relieved the previously described transrepression between nuclear receptors and either AP-1 or NFkappaB. Overall, these results suggest that the nuclear receptor coactivator ASC-2 also mediates transactivations by SRF, AP-1, and NFkappaB, which may contribute to the putative, ASC-2-mediated tumorigenesis.

3T3 Cells↗

Characterization of an alkali-extracted peptidoglycan from Korean Ganoderma lucidum.

The biologically active peptidoglycan was purified from the alkali fraction of the fruiting bodies of Ganoderma lucidum and the composition of the peptidoglycan was investigated by conventional analyses. The alkali-extracted peptidoglycan showed differences in chemical compositions from the water-extracted. The alkali-extracted peptidoglycan contained 6.9% protein and 75.9% carbohydrates composed mainly of beta-glucose, mannose, and alpha-glucose. The molecular weight range of the peptidoglycan was determined as 2,000 kDa-17 kDa. The peptidoglycan is considered to be a hybrid molecule of polysaccharide chains covalently bound as a side chain to the polypeptide core.

Amino Acids↗