Biomedical subjects

Soo-Kyung Lee

Publications and source records attributed to Soo-Kyung Lee.

At least 19 recordsLinked to original sources

PubMed2006

Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferases.

Activating signal cointegrator-2 (ASC-2), a coactivator of multiple transcription factors that include retinoic acid receptor (RAR), associates with histone H3-K4 methyltranferases (H3K4MTs) MLL3 and MLL4 in mixed-lineage leukemia. Here, we show that mice expressing a SET domain mutant of MLL3 share phenotypes with isogenic ASC2+/- mice and that expression and H3-K4 trimethylation of RAR target gene RAR-beta2 are impaired in ASC-2-null mouse embryo fibroblasts (MEFs) or in MEFs expressing siRNAs against both MLL3 and MLL4. We also show that MLL3 and MLL4 are found in distinct ASC-2-containing complexes rather than in a common ASC-2 complex, and they are recruited to RAR-beta2 by ASC-2. In contrast, RAR-beta2 expression is intact in MEFs devoid of menin, a component of MLL1 and MLL2 H3K4MT complexes. These results suggest that ASC-2 confers target gene specificity to MLL3 and MLL4 H3K4MT complexes and that recruitment of H3K4MTs to their target genes generally involves interactions between integral components of H3K4MT complexes and transcription factors.

Animals↗

PubMed2006

Calcium activation of the LMO4 transcription complex and its role in the patterning of thalamocortical connections.

Lasting changes in neuronal connectivity require calcium-dependent gene expression. Here we report the identification of LIM domain-only 4 (LMO4) as a mediator of calcium-dependent transcription in cortical neurons. Calcium influx via voltage-sensitive calcium channels and NMDA receptors contributes to synaptically induced LMO4-mediated transactivation. LMO4-mediated transcription is dependent on signaling via calcium/calmodulin-dependent protein (CaM) kinase IV and microtubule-associated protein (MAP) kinase downstream of synaptic stimulation. Coimmunoprecipitation experiments indicate that LMO4 can form a complex with cAMP response element-binding protein (CREB) and can interact with cofactor of LIM homeodomain protein 1 (CLIM1) and CLIM2. To evaluate the role of LMO4 in vivo, we examined the consequences of conditional loss of lmo4 in the forebrain, using the Cre-Lox gene-targeting strategy. The organization of the barrel field in somatosensory cortex is disrupted in mice in which lmo4 is deleted conditionally in the cortex. Specifically, in contrast to controls, thalamocortical afferents in conditional lmo4 null mice fail to segregate into distinct barrel-specific domains. These observations identify LMO4 as a calcium-dependent transactivator that plays a key role in patterning thalamocortical connections during development.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Reaching Asian Americans: sampling strategies and incentives.

Reaching and recruiting representative samples of minority populations is often challenging. This study examined in Chinese and Korean Americans: 1) whether using two different sampling strategies (random sampling vs. convenience sampling) significantly affected characteristics of recruited participants and 2) whether providing different incentives in the mail survey produced different response rates. We found statistically significant, however mostly not remarkable, differences between random and convenience samples. Offering monetary incentives in the mail survey improved response rates among Chinese Americans, while offering a small gift did not improve response rates among either Chinese or Korean Americans. This information will be useful for researchers and practitioners working with Asian Americans.

Asian↗

PubMed2006

T-Box transcription factor Tbx20 regulates a genetic program for cranial motor neuron cell body migration.

Members of the T-box transcription factor family (Tbx) are associated with several human syndromes during embryogenesis. Nevertheless, their functions within the developing CNS remain poorly characterized. Tbx20 is expressed by migrating branchiomotor/visceromotor (BM/VM) neurons within the hindbrain during neuronal circuit formation. We examined Tbx20 function in BM/VM cells using conditional Tbx20-null mutant mice to delete the gene in neurons. Hindbrain rhombomere patterning and the initial generation of post-mitotic BM/VM neurons were normal in Tbx20 mutants. However, Tbx20 was required for the tangential (caudal) migration of facial neurons, the lateral migration of trigeminal cells and the trans-median movement of vestibuloacoustic neurons. Facial cell soma migration defects were associated with the coordinate downregulation of multiple components of the planar cell polarity pathway including Fzd7, Wnt11, Prickle1, Vang1 and Vang2. Our study suggests that Tbx20 programs a variety of hindbrain motor neurons for migration, independent of directionality, and in facial neurons is a positive regulator of the non-canonical Wnt signaling pathway.

Animals↗

PubMed2005

Physicochemical characterization of poly(L-lactic acid) and poly(D,L-lactide-co-glycolide) nanoparticles with polyethylenimine as gene delivery carrier.

Polymer nanoparticles have been used as non-viral gene delivery systems and drug delivery systems. In this study, biodegradable poly(L-lactic acid) (PLA)/polyethylenimine (PEI) and poly(D,L-lactide-co-glycolide) (PLGA)/PEI nanoparticles were prepared and characterized as gene delivery systems. The PLA/PEI and PLGA/PEI nanoparticles, which were prepared by a diafiltration method, had spherical shapes and smooth surface characteristics. The size of nanoparticles was controlled by the amount of PEI, which acted as a hydrophilic moiety, which effectively reduced the interfacial energy between the particle surface and the aqueous media. The nanoparticles showed an excellent dispersive stability under storage in a phosphate-buffered saline solution for 12 days. The positive zeta-potentials for the nanoparticles decreased and changed to negative values with increasing plasmid DNA (pDNA) content. Agarose gel electrophoresis showed that the complex formation between the nanoparticles and the pDNA coincided with the zeta-potential results. The results of in vitro transfection and cell viability on HEK 293 cells indicated that the nanoparticles could be used as gene delivery carriers.

Cell Survival↗

PubMed2005

Small CTD phosphatases function in silencing neuronal gene expression.

Neuronal gene transcription is repressed in non-neuronal cells by the repressor element 1 (RE-1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) complex. To understand how this silencing is achieved, we examined a family of class-C RNA polymerase II (RNAPII) carboxyl-terminal domain (CTD) phosphatases [small CTD phosphatases (SCPs) 1 to 3], whose expression is restricted to non-neuronal tissues. We show that REST/NRSF recruits SCPs to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells. Phosphatase-inactive forms of SCP interfere with REST/NRSF function and promote neuronal differentiation of P19 stem cells. Likewise, small interfering RNA directed to the single Drosophila SCP unmasks neuronal gene expression in S2 cells. Thus, SCP activity is an evolutionarily conserved transcriptional regulator that acts globally to silence neuronal genes.

Animals↗

PubMed2005

A Korean herbal medicine, Panax notoginseng, prevents liver fibrosis and hepatic microvascular dysfunction in rats.

We assessed the prevention of hepatic fibrogenesis by water-extract of Panax notoginseng Buck F.H. Chen. (Arialiaceae) root (PNS) in Long-Evans rats with cinnamon coat color (LEC rats). LEC rats were divided into three groups A, fed on a basal diet (BD); B, fed on BD plus 1% PNS; and C), fed on BD plus 0.005% lycopene as a control. All rats were sacrificed at 26 weeks of age. The percentage of the total area involved by fibrosis was 1.46 +/- 0.47 in group A, 0.83 +/- 0.10 in B (P=0.0030, B vs A) and 0.91 +/- 0.45 in C (P=0.0035, C vs. A). The percentage of the total area that was stained for alpha-SMA was 0.56 +/- 0.34 in group A, 0.15 +/- 0.02 in B (P=0.0016, B vs. A and 0.11 +/- 0.01 in C (P=0.0025, C vs. A. In group B, malondialdehyde (MDA) in the liver was lower than in group C (P=0.007). In group C, the concentration of iron in the liver was lower than in group A (P=0.0053). Thus, PNS suppressed fibrogenesis through reduced generation of lipid peroxides. The mechanisms of this preventive effect of fibrogenesis with PNS were suggested to inhibit the stellate cell activity. Second objective of this study was to determine whether PNS affects hepatic microvascular dysfunction elicited by gut ischemia and reperfusion (I/R), since gut I/R causes hepatic microvascular dysfunction, and to investigate the role of nitric oxide (NO). Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor the number of non-perfused sinusoids (NPS). In another set of experiments, PNS (1 g/kg per day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered. In control rats, gut I/R elicited increases in the number of NPS, and plasma TNF-alpha and ALT activities, and these changes were mitigated by the pretreatment with PNS. Pretreatment with an NO synthase inhibitor diminished the protective effects of PNS on the increase in NPS and plasma TNF-alpha levels, but not its effect on the increase in plasma ALT activities. Pretreatment with PNS increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST. These results suggest that PNS attenuates the gut I/R-induced hepatic microvascular dysfunction and inflammatory responses such as TNF-alpha production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti-inflammatory effect.

Actins↗

PubMed2005

Olig2 and Ngn2 function in opposition to modulate gene expression in motor neuron progenitor cells.

Spinal motor neurons and oligodendrocytes are generated sequentially from a common pool of progenitors termed pMN cells. Olig2 is a bHLH-class transcription factor in pMN cells, but it has remained unclear how its transcriptional activity is modulated to first produce motor neurons and then oligodendrocytes. Previous studies have shown that Olig2 primes pMN cells to become motor neurons by triggering the expression of Ngn2 and Lhx3. Here we show that Olig2 also antagonizes the premature expression of post-mitotic motor neuron genes in pMN cells. This blockade is counteracted by Ngn2, which accumulates heterogeneously in pMN cells, thereby releasing a subset of the progenitors to differentiate and activate expression of post-mitotic motor neuron genes. The antagonistic relationship between Ngn2 and Olig2 is mediated by protein interactions that squelch activity as well as competition for shared DNA-binding sites. Our data support a model in which the Olig2/Ngn2 ratio in progenitor cells serves as a gate for timing proper gene expression during the development of pMN cells: Olig2(high) maintains the pMN state, thereby holding cells in reserve for oligodendrocyte generation, whereas Ngn2(high) favors the conversion of pMN cells into post-mitotic motor neurons.

Animals↗

PubMed2005

Validity of self-reported weight and height: comparison between immigrant and non-immigrant Mexican Americans in NHANES III.

This study examined whether 1) the immigrant Mexican Americans reported weight and height differently from the non-immigrant Mexican Americans and, 2) self-reporting errors influenced weight classification. A U.S. national sample of 3085 Mexican Americans from the third National Health and Nutrition Examination Survey was used to investigate validity using paired t-tests, multiple linear regressions, sensitivity and specificity. While immigrant Mexican American women reported their weight and height higher than non-immigrant women, no significant differences were found between immigrant and non-immigrant Mexican American men. Sensitivity and specificity of weight classification with self-reported weight and height were not different between immigrant and non-immigrant Mexican Americans; however, underweight Mexican Americans showed the lowest sensitivity. Therefore, self-reported weight and height can be used for the purpose of weight classification with immigrant and non-immigrant Mexican Americans, with an exception of underweight Mexican Americans.

Adult↗

PubMed2005

The LIM domain-only protein LMO4 is required for neural tube closure.

Nuclear LIM domain-only proteins (LMOs), which consist of two closely spaced 50 amino acid Zn2+-finger protein interaction modules mediate interactions between several classes of transcription factors important for development. LMO2 is necessary for development of the entire hematopoietic system and overexpression of LMO1 or LMO2 results in human acute T cell leukemia. LMO4 is the most widely expressed LMO but its normal function is unknown. During development, LMO4 is expressed in dividing neuroepithelial cells within the ventricular zone along the entire rostrocaudal axis of the nervous system. In telencephalic and spinal cord regions of the CNS, LMO4 is highly expressed in ventral but is low in dorsal proliferating neuroepithelial cells. To understand the role of LMO4 during mouse development, we generated a homozygous null mutation in the gene. We found that LMO4 is required for proper closure of the anterior neural tube. In the absence of LMO4, elevation, bending, and proliferation of the ventral neural epithelium and consequent fusion of the prospective dorsal ends of the neural tube do not occur. LMO4 mutant mice die embryonically and exhibit exencephaly, which is associated with abnormal patterns of cell proliferation and with high levels of apoptotic cell death within the neuroepithelium. LMO4 is thus essential for normal patterns of proliferation and for survival of neural epithelial cells in the rostral neural tube. LMO4 is also expressed in Schwann cell progenitors after these contact neurites, a process mediated in part by neuregulin (Nrg).

Adaptor Proteins, Signal Transducing↗

PubMed2005

Parity and body weight in the United States: differences by race and size of place of residence.

OBJECTIVE: In women, parity has been studied in relation to body weights. This study examined whether and how relationships between parity and body weight differ by race and size of place of residence, adjusting for sociodemographic factors (age, income, education, working status, and marital status) and health behaviors (alcohol consumption, birth control pills, diet, physical activity, and smoking). RESEARCH METHODS AND PROCEDURES: A U.S. national sample of 3398 white and black women from the Third National Health and Nutrition Examination Survey was used to study the relationships using multiple linear regression analysis. RESULTS: The parity-weight relationships varied by race and size of place of residence. After adjusting for the covariates, significant relationships between parity and body weight were found only in black women in metropolitan areas and white women in non-metropolitan areas. Compared with women with no children, white women with two children living in non-metropolitan areas tended to have lower BMIs, whereas black women in metropolitan areas with one or two children showed higher BMIs. DISCUSSION: Overall, the parity-weight relationships in these groups of women were not strong or linear. The parity-weight relationships of black women in non-metropolitan areas warrant further examination.

Adult↗

PubMed2005

Group distal movement of teeth using microscrew implant anchorage.

The purpose of this study was to quantify the treatment effects of distalization of the maxillary and mandibular molars using microscrew implants. The success rate and clinical considerations in the use of the microscrew implants were also evaluated. Thirteen patients who had undergone distalization of the posterior teeth using forces applied against microscrew implants were selected. Among them, 11 patients had mandibular microscrew implants and four patients had maxillary implants, including two patients who had both maxillary and mandibular ones at the same time. The maxillary first premolar and first molars showed significant distal movement, with no significant distal movement of the anterior teeth. The mandibular first premolar and first and second molars showed significant distal movement, but no significant movement of the mandibular incisor was observed. The microscrew implant success rate was 90% over a mean application period of 12.3 +/- 5.7 months. The results might support the use of the microscrew implants as an anchorage for group distal movement of the teeth.

Adolescent↗

PubMed2005

Tumor initiation inhibition through inhibition COX-1 activity of a traditional Korean herbal prescription, Geiji-Bokryung-Hwan, in human hepatocarcinoma cells.

Some Korean and oriental herbal prescriptions used for a syndrome expressed as chest paralysis and heartache are thought to be effective for angina pectoris. We investigated the effects of an oriental medicinal prescription, Geiji-Bokryung-Hwan (GBH) consisting of herbs of Cinnamomi Ramulus, Poria Cocos Hoelen (Pachymae Fungus), Moutan Cortex Radicis, Paeoniae Radix, and Persicae Semen, on growth-inhibitory activity and cancer chemopreventive activity in assays representing three major stages of carcinogenesis. The GBH was found to act as an potent inhibitor of cyclooxygenase (COX)-1 only but not as COX-2 inhibitor. Furthermore, the extract mediated anti-inflammatory effects and inhibited COX-associated hydroperoxidase functions (anti-promotion activity). Inhibitory effect of the GBH on the growth of cancer cell lines such as HepG2 cell and Hep3B cell was shown. These data suggest that GBH extracts merit investigation as a potential cancer chemopreventive agent in humans, especially in hepatological cancers.

Anticarcinogenic Agents↗

PubMed2005

The prevalence of wasting, but not stunting, has improved in the Democratic People's Republic of Korea.

The Democratic People's Republic of Korea (DPRK) is one of the nutritionally vulnerable countries of the world. The objectives of this paper were to determine the current prevalence of undernutrition among children using data from the latest national survey and to compare the findings with those from the previous national survey in 1997. In 2002 with cooperation from UNICEF and the World Food Program (WFP), the government of the DPRK conducted a survey of 6000 households with children < 7 y old using multiple-stage sampling methods. Data were collected for sociodemographic variables, use of WFP food aid, and anthropometric measures of the youngest child in the household. The prevalence of stunting (height for age Z-score less than -2.0) in all children was 39.4% (40.2 and 38.5% for boys and girls, respectively). The prevalence of wasting (weight for height Z-score less than -2.0) was 8.2% in all children (9.1 and 7.3% for boys and girls, respectively). Although the prevalence of wasting has decreased from 1997 (16.5%) to 2002 (8.2%), the prevalence of stunting has not changed between those years, 38.2 vs. 39.4%. Thus, we conclude that acute undernutrition is decreasing in the DPRK, but chronic undernutrition that results in stunting is still highly prevalent. Continued surveillance of nutritional status of children in the DPRK is warranted given the continued state of undernutrition in that country.

Adult↗

PubMed2004

Analysis of embryonic motoneuron gene regulation: derepression of general activators function in concert with enhancer factors.

The underlying transcriptional mechanisms that establish the proper spatial and temporal pattern of gene expression required for specifying neuronal fate are poorly defined. We have characterized how the Hb9 gene is expressed in developing motoneurons in order to understand how transcription is directed to specific cells within the developing CNS. We found that non-specific general-activator proteins such as E2F and Sp1 are capable of driving widespread low level transcription of Hb9 in many cell types throughout the neural tube; however, their activity is modulated by specific repressor and activator complexes. The general-activators of Hb9 are suppressed from triggering inappropriate transcription by repressor proteins Irx3 and Nkx2.2. High level motoneuron expression is achieved by assembling an enhancesome on a compact evolutionarily-conserved segment of Hb9 located from -7096 to -6896. The ensemble of LIM-HD and bHLH proteins that interact with this enhancer change as motoneuron development progresses, facilitating both the activation and maintenance of Hb9 expression in developing and mature motoneurons. These findings provide direct support for the derepression model of gene regulation and cell fate specification in the neural tube, as well as establishing a role for enhancers in targeting gene expression to a single neuronal subtype in the spinal cord.

Animals↗

PubMed2004

Mammalian two-hybrid assay for detecting protein-protein interactions in vivo.

Mammalian two-hybrid assay is a convenient, powerful tool to investigate protein-protein interactions in vivo. In particular, this method has a major advantage over the better known yeast version in that one can study interactions between mammalian proteins that may not fold correctly in yeast or that require post-translational modification or external stimulation that are not present in yeast.

Animals↗

PubMed2003

Interactions between activating signal cointegrator-2 and the tumor suppressor retinoblastoma in androgen receptor transactivation.

Activating signal cointegrator-2 (ASC-2), a cancer-amplified transcription coactivator of nuclear receptors and numerous other transcription factors, was previously shown to contain two LXXLL motifs, each of which interacts with a distinct set of nuclear receptors. In this work, we showed that ASC-2 has an indirect, separate binding site for androgen receptor (AR). Interestingly, this region overlapped with the direct interaction interfaces with the tumor suppressor retinoblastoma (Rb). Although ASC-2 alone stimulated AR transactivation in cotransfections of HeLa cells, ectopic expression of Rb effected ASC-2 to act as a transcription coactivator of AR in Rb-null Saos2 cells. These results, along with the previous report in which AR was shown to directly interact with Rb (Yeh, S., Miyamoto, H., Nishimura, K., Kang, H., Ludlow, J., Hsiao, P., Wang, C., Su, C., and Chang C. (1998) Biochem. Biophys. Res. Commun. 248, 361-367), suggest that the AR-ASC-2 interactions in vivo may involve Rb. Thus, ASC-2 appears to contain at least three distinct nuclear receptor interaction domains.

Amino Acid Motifs↗

PubMed2003

Socio-economic, dietary, activity, nutrition and body weight transitions in South Korea.

OBJECTIVE: Socio-economic development influences many factors that affect health, especially diet and nutrition. This investigation proposes that a system of transitions occur as societies develop, with socio-economic, physical activity, dietary, nutrition and body weight transitions operating in relationship with each other. This model of transitions was examined empirically using South Korea as an example of a nation that has undergone considerable changes. DESIGN: Data were drawn from published government reports: the Korean National Nutrition Survey and annual reports at the national level for the years between 1969 and 1993. The socio-economic transition was assessed by gross national product. The physical activity transition was assessed using annual proportions of the population involved in primary, secondary and tertiary industries, as well as the number of cars and driver's licences. The dietary transition was measured by plant and animal food consumption. The nutrition transition was assessed by percentages of energy from carbohydrate, protein and fat. The body weight transition was measured by body mass index calculated from the average height and weight of adolescents. RESULTS: Results revealed that the transitions were highly correlated as expected, with the socio-economic transition exhibiting major changes. South Koreans tended to decrease their physical activity and plant food consumption, and to increase animal food consumption, percentage of energy from dietary fat and body weight, in relationship to the socio-economic transition. CONCLUSION: Examining a system of transitions on a national level in one country that has undergone rapid economic development may provide a strategy for examining how such transitions operate in other nations.

Body Weight↗