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Biomedical subjects

Y Lee

Publications and source records attributed to Y Lee.

At least 55 records · Page 3Linked to original sources

Fixed-effect versus random-effect models for evaluating therapeutic preferences.

A preference trial is a special form of cross-over trial where clinical conditions determine when patients change treatment, in a prescribed order. This leads to binary responses with variable lengths. In cross-over trials with normal responses, patient effect may be treated as either fixed or random. However, with binary responses, random- and fixed-effect assumptions may lead to very different conclusions, so that one is no longer an alternative to the other.

Asthma↗

PPAR alpha is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue.

Adenovirus-induced hyperleptinemia causes rapid disappearance of body fat in normal rats, presumably by up-regulating fatty acid oxidation within white adipocytes. To determine the role of peroxisomal proliferation-activated receptor (PPAR)alpha expression, which was increased during the rapid loss of fat, we infused adenovirus-leptin into PPAR alpha(-/-) and PPAR alpha(+/+) mice. Despite similar degrees of hyperleptinemia and reduction in food intake, epididymal fat pad weight declined 55% in wild-type but only 6% in PPAR alpha(-/-) mice; liver triacylglycerol fell 39% in the wild-type group but was unchanged in PPAR(-/-) mice. Carnitine palmitoyl transferase-1 mRNA rose 52% in the wild-type mice but did not increase in PPAR alpha(-/-) mice. PPAR gamma coactivator-1 alpha rose 3-fold in the fat and 46% in the liver of wild-type mice but was unchanged in PPAR alpha(-/-) mice. Although AMP-activated protein kinase could not be implicated in the lipopenic actions of hyperleptinemia, acetyl CoA carboxylase protein was reduced in the liver of wild-type but not in PPAR alpha(-/-) mice. Thus, in PPAR alpha(-/-) mice, up-regulation of carnitine palmitoyl transferase-1 mRNA in fat, down-regulation of acetyl CoA carboxylase in liver, and up-regulation of PPAR gamma coactivator-1 alpha mRNA in both tissues are abolished, as is the reduction in their triacylglycerol content.

AMP-Activated Protein Kinases↗

Skin thickness of Korean adults.

Skin thickness varies considerably between different races and age-groups, between men and women, and between different regions of the body surface. A few authors reported the skin thickness of different regions of the body, but no detailed study have been performed on Asian. We performed 452 biopsies on 28 different regions of the normal skin of Korean men and women. The specimens were stained with hematoxylin-eosin and measured microscopically. The thickness of the skin (epidermis plus dermis) ranged from 521 to 1977 microm; the eyelid, prepuce, and inguinal skin was thinnest (521-626 microm), and the back was thickest (1977 microm). The thickness of the epidermis varied from 31 to 637 microm; skin thickness in the prepuce, eyelid, supraclavicular region, postauricular region, and axilla ranged from 31 to 71 microm; the buttock, dorsum of the hand, and dorsum of the foot were relatively thick (138-189 microm); the palm and sole were thickest (601-637 microm). The thickness dermis varied from 469 to 1942 microm; skin thickness in the eyelid, prepuce, inguinal region, and postauricular region ranged from 469 to 645 microm; the buttock, chest, and anterior neck were relatively thick (1318-1586 microm); the back was thickest (1942 microm). The epidermis accounted for 3.7-16.8% of the entire skin in most regions, except in the palm and sole (40.6-44.6%). Thickness data may be useful in harvesting full- or split-thickness skin grafts.

Adolescent↗

A simple method for the detection of neurologic disorders associated with CAG repeat expansion using PCR-microtiter plate hybridization.

A new screening method was developed for the detection of CAG expanded alleles in patients with hereditary ataxia using polymerase chain reaction-based microtiter plate hybridization (PCR-MPH). The system can be applied to detect pathologic alleles by hybridization with the immobilized (CAG)48 repeat probe derived from the unrelated gene 'ERDA1' except for the CAG repeats. We examined 10 individuals with SCA3, 10 with Huntington disease and 30 normal controls (31 controls for SCA3) using this method. The results showed that a clear discrimination was possible in all cases. We suggest that this system be made available for mass screening of patients with hereditary ataxia disorders. This report is the first to demonstrate that a PCR-MPH system can be successfully applied to DNA size differentiation in addition to base pair mismatches. Also, our design of the probe is unique in that the probe motif stem from the unrelated gene sequence and not from the synthetic oligonucleotides.

Alleles↗

Intraperitoneal gene delivery mediated by a novel cationic liposome in a peritoneal disseminated ovarian cancer model.

We have previously synthesized a new cationic liposome that displays high efficiency and low toxicity, 3 beta[l-ornithinamide-carbamoyl] cholesterol (O-Chol), using solid-phase synthesis. In this study, O-Chol was applied to in vitro and in vivo models of ovarian cancer. Intraperitoneal gene delivery for peritoneal disseminated ovarian cancer in nude mice was achieved using a stable chloramphenicol acetyl transferase (CAT)-expressing ovarian cancer cell line (OV-CA-2774/CAT), which allowed us to quantify the exact tumor burden of organs. When luciferase and beta-galactosidase genes were used as reporter genes, O-Chol showed better efficiency than other commercial transfection reagents such as lipofectin, lipofectAMINE, DC-Chol, and FuGENE 6, both in vitro and in vivo. Moreover, the transfection efficiency of this new cationic lipid reagent remained high in serum-containing medium and under serum-free conditions. Furthermore, in vivo transfection with O-Chol showed high levels of gene expression specific to peritoneal tumor cells. Consequently, the O-Chol:DNA lipoplex appears to offer potential advantages over other commercial transfection reagents because of (1) its higher level of gene expression in vitro and in vivo; (2) its reduced susceptibility to serum inhibition; and (3) its highly selective transfection into tumor cells. These results suggest that the O-Chol:DNA lipoplex is a promising tool in gene therapy for patients with peritoneal disseminated ovarian cancer.

Animals↗

Diet quality, nutrient intake, weight status, and feeding environments of girls meeting or exceeding the American Academy of Pediatrics recommendations for total dietary fat.

The American Academy of Pediatrics (AAP) recommends that children consume no more than 30% but no less than 20% of energy as dietary fat intake, and this recommendation is accompanied by suggestions that fat calories should be replaced by eating more grain products, fruits, vegetables, low fat dairy products, beans, lean meat, poultry, fish, and other protein rich foods. In comparing diets of girls meeting this AAP recommendation with girls who consumed diets higher in fat, we noted that girls meeting recommendations had diets that came closer to meeting other dietary recommendations for several food groups and had higher intake of several key micronutrients. Dietary fat was also associated with body fat and weight status. Children's fat intake was also related to mothers' dietary fat intake, and nutrient intake patterns were similar for mothers and daughters. Finally, mothers of girls consuming higher fat diets reported using more restriction and pressure to eat in feeding their daughters. These findings provide additional support for the AAP recommendation to limit total dietary fat. Findings reveal that mothers' use of controlling feeding practices are not effective in fostering healthier diets among children, and that mothers' own eating may be more influential than their attempts to control children's intake.

Adolescent↗

Application of recombinant fluorescent mammalian cells as a toxicity biosensor.

With respect to developing a more sensitive biosensor, a recombinant fluorescent Chinese Hamster Ovary cell line was used for the monitoring of various toxicants. Both cell lines, EFC-500 and KFC-A10, were able to detect toxicants sensitively. They were characterized with mitomycin C and gamma-ray as genotoxicants and bisphenol A, nonylphenol, ziram and methyl bromide as possible and known EDCs. When compared to each other, the response of KFC-A10 was generally more informative and sensitive. Compared to typical bacterial biosensor systems, these cell lines offered a sensitivity of 2- to 50-fold greater for the tested chemicals. Based on these results, the use of mammalian cells offers a sensitive biosensor system that is not only fast, cheap and reproducible but also capable of monitoring the endocrine-like characteristics of environmental toxicants.

Animals↗

Reduction of sludge by ozone treatment and production of carbon source for denitrification.

The feasibility of ozone treatment of municipal sludge for sludge reduction and carbon source production has been investigated. Significant accumulation of solubilized organics and unsettlable micro-solids (UMS) was observed at relatively low ozone dosages while mineralization became dominant at higher dosages. Batch denitrification experiments showed that the solubilized organics and the UMS could be utilized as carbon sources for nitrogen removal. In terms of overall sludge reduction, 54% reduction of the total sludge mass could be achieved by ozone treatment at 0.2 g-O3/g-MLSS.

Carbon↗

Conjugation of low-molecular-weight heparin and deoxycholic acid for the development of a new oral anticoagulant agent.

BACKGROUND: Heparin administration is usually limited to intravenous or subcutaneous injection. Oral delivery of heparin is an alternative to this and has been in great demand for treating patients who are at a high risk of deep vein thrombosis or pulmonary embolism. In this study, new heparin derivatives were synthesized to enhance the oral absorption of heparin in the gastrointestinal tract. Methods and Results- By using heparin of 3000 Da [LMWH(3 kDa)], heparin of 6000 Da [LMWH(6 kDa)], and unfractionated heparin (UFH), we synthesized 3 kinds of conjugates of heparin and deoxycholic acid (DOCA): LMWH(3 kDa)-DOCA, LMWH(6 kDa)-DOCA, and UFH-DOCA. After oral administration of 100 mg/kg of heparin-DOCA, the maximum activated partial thromboplastin times of the LMWH(3 kDa)-DOCA, LMWH(6 kDa)-DOCA, and UFH-DOCA were 31.0+/-6.0, 87.8+/-11.1, and 51.0+/-8.7 seconds, respectively. The peak plasma concentrations of LMWH(3 kDa)-DOCA, LMWH(6 kDa)-DOCA, and UFH-DOCA were 0.06+/-0.02, 0.76+/-0.15, and 0.41+/-0.13 IU/mL, respectively. The bioavailability of LMWH(6 kDa)-DOCA at the 20-mg/kg dosage was calculated to be 7.8%. CONCLUSIONS: LMWH(6 kDa)-DOCA was found to have a high anticoagulant effect when administered orally and could be used as a new oral anticoagulant agent. Furthermore, the present work proposed a new method for oral delivery of macromolecules and polysaccharide drugs.

Administration, Oral↗

Subunit interaction maps for the regulatory particle of the 26S proteasome and the COP9 signalosome.

The 26S proteasome plays a major role in eukaryotic protein breakdown, especially for ubiquitin-tagged proteins. Substrate specificity is conferred by the regulatory particle (RP), which can dissociate into stable lid and base subcomplexes. To help define the molecular organization of the RP, we tested all possible paired interactions among subunits from Saccharomyces cerevisiae by yeast two-hybrid analysis. Within the base, a Rpt4/5/3/6 interaction cluster was evident. Within the lid, a structural cluster formed around Rpn5/11/9/8. Interactions were detected among synonymous subunits (Csn4/5/7/6) from the evolutionarily related COP9 signalosome (CSN) from Arabidopsis, implying a similar quaternary arrangement. No paired interactions were detected between lid, base or core particle subcomplexes, suggesting that stable contacts between them require prior assembly. Mutational analysis defined the ATPase, coiled-coil, PCI and MPN domains as important for RP assembly. A single residue in the vWA domain of Rpn10 is essential for amino acid analog resistance, for degrading a ubiquitin fusion degradation substrate and for stabilizing lid-base association. Comprehensive subunit interaction maps for the 26S proteasome and CSN support the ancestral relationship of these two complexes.

Arabidopsis Proteins↗

Structure-reactivity relationships in the pyridinolysis of N-methyl-N-arylcarbamoyl chlorides in dimethyl sulfoxide.

Nucleophilic substitution reactions of N-methyl-N-arylcarbamoyl chlorides (YC(6)H(4)N(CH(3))COCl) with pyridines (XC(5)H(4)N) have been investigated in dimethyl sulfoxide at 45.0 degrees C. A striking trend in the selectivity parameters is that they are constant within experimental errors, rho(X) = -2.25 +/- 0.03, beta(X) = 0.42 +/- 0.01, and rho(Y) = 1.10 +/- 0.06, with changing reactivities of the electrophiles (deltasigma(Y)) and nucleophiles (deltasigma(X)), respectively, and this leads to a vanishingly small cross-interaction constant, rho(XY) approximately equals beta(XY) approximately equals 0. The rate data can be expressed in the Ritchie N(+) type equation. Based on this and other results, the mechanism of nucleophile (pyridine) addition to the resonance- stabilized carbocation is proposed. It has been shown from the definition of beta(XY) (and rho(XY)) together with the Marcus equation that the high intrinsic barrier, DeltaG(0), in the intrinsic-barrier controlled reaction series is a prerequisite for such reactions in which the cross-interaction vanishes and the N(+) relationship holds.

Journal Article↗

Maximization of acetic acid production in partial acidogenesis of swine wastewater.

Swine wastewater was biologically treated to produce short-chain volatile organic acids (VOAs) in laboratory-scale continuously stirred tank reactors. The maximum production rates of acetic and butyric acids associated with simultaneous changes in pH and hydraulic retention time (HRT) were investigated, in which the degree of acidification of swine wastewater to the short-chain VOAs was <25% of influent chemical oxygen demand (COD) concentration. A constant inoculum system was used to minimize the experimental error due to the use of inconsistent inoculum. The inoculum system was operated with synthetic wastewater at 6000 mg soluble chemical oxygen demand per liter (pH 6.0) and 35 degrees C at 0.5 day hydraulic retention time. Response surface methodology was applied successfully to determine the optimum physiological condition for which the maximum rate of acetic acid production occurred, which was pH 5.90 and 0.88 day hydraulic retention time at 35 degrees C. The partial acidification process to manage swine waste should be operated in the optimum condition for acetic acid production because the optimum operating condition for butyric acid production approached the washout point.

Acetic Acid↗

Interaction of poly(A) polymerase with the 25-kDa subunit of cleavage factor I.

Mammalian poly(A) polymerase (PAP), a key enzyme in the pre-mRNA 3'-end processing reaction, carries the catalytic domain in the N-terminal region, an RNA binding domain, two nuclear localization signals, and a serine/threonine-rich regulatory domain in the C-terminal region. Using LexA-based yeast two-hybrid screening, we identified a cDNA encoding the 25-kDa subunit of cleavage factor I (CFI-25) as a protein that interacts with the C-terminal region of mouse PAP. The glutathione S-transferase pull-down assay and the immunoprecipitation experiment revealed that PAP directly interacts with CFI-25 and that the C-terminal 69 residues of PAP and the N-terminal 60 residues of CFI-25 are sufficient for the interaction between CFI-25 and PAP. Since CFI is known to function in the assembly of the pre-mRNA 3'-processing complex, this interaction may play an important role in the assembly of the processing complex and/or in the regulation of PAP activity within the complex.

Animals↗

Identification of a structural motif of 23S rRNA interacting with 5S rRNA.

To identify RNA motifs interacting with 5S rRNA, a systematic evolution of ligands by exponential enrichment experiment was applied. Some of the resulting RNA aptamers contained a consensus sequence similar to the sequence in the loop region of helix 89 of 23S rRNA. We show that the synthetic helix 89 RNA motif indeed interacted with 5S rRNA and that the region around loop B of 5S rRNA was involved in this interaction. These results suggest the presence of a novel RNA-RNA interaction between 23S rRNA and 5S rRNA which may play an important role in the ribosome function.

Base Pairing↗

The role of PDR13 in tolerance to high copper stress in budding yeast.

PDR13 in Saccharomyces cerevisiae contributes to drug resistance via sequential activation of PDR1 and PDR5. In this study, we found that a PDR13 deletion mutant was hypersensitive to Cu(2+) compared to the wild-type counterpart. The Cu(2+) tolerance mechanism mediated by Pdr13 does not seem to involve Pdr1 or Pdr5, since mutants harboring a deletion of either the PDR1 or PDR5 gene did not show elevated Cu(2+) sensitivity. Instead, we found that the PDR13 null mutant could not express CUP1 or CRS5 metallothionein at wild-type levels when subjected to high Cu(2+) stress. These results suggest that Pdr13 contributes to high Cu(2+) tolerance of S. cerevisiae, at least in part, via a mechanism involving metallothionein expression.

ATP-Binding Cassette Transporters↗

Effects of subchronic lithium chloride treatment on G-protein subunits (Golf, Ggamma7) and adenylyl cyclase expressed specifically in the rat striatum.

Lithium salt has been widely used as a treatment for mania, but the mechanism of its effect remains unknown. Previously, by studying c-fos expression, we showed that the striatum was a possible target region for the antimanic effects of lithium salt. The present study focused on the effect of subchronic lithium chloride treatment on G-proteins (Golf, Ggamma7) and adenylyl cyclase type V, which are expressed specifically in the rat striatum. Subchronic lithium chloride treatment significantly increased the level of Golf protein, a stimulant alpha-subunit of G-protein, by 53.5% (P<0.01), but the levels of Ggamma7 and adenylyl cyclase type V did not change. This increased level of Golf protein was found after 2 weeks of lithium chloride treatment, but not after 1 week, and the level returned to the basal level 1 week after withdrawal of lithium chloride. This result suggests that the level of Golf protein increases to compensate for the suppression of the adenylyl cyclase system by lithium, and that this increase may account for the "rebound" phenomenon, which is the relapse observed after abrupt discontinuation of lithium salt treatment.

Adenylyl Cyclases↗

Role of the sequence of the rne-dependent site in 3' processing of M1 RNA, the catalytic component of Escherichia coli RNase P.

The 3' processing of M1 RNA, the catalytic component of Escherichia coli RNase P, occurs by two pathways involving multiple steps. The precursor of M1 RNA has an rne-dependent site downstream of the processing site, whose sequence variation affects the processing efficiency. In this study, we showed that the sequence itself of the rne-dependent site possessed the ability to determine the processing pathways and that it also affected the cleavage specificity with the generation of the processing products at one nucleotide upstream or downstream of the normal cleavage sites.

Base Sequence↗