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Biomedical subjects

Y Park

Publications and source records attributed to Y Park.

At least 127 records · Page 7Linked to original sources

Evidence that the trans-10,cis-12 isomer of conjugated linoleic acid induces body composition changes in mice.

We investigated the effects of conjugated linoleic acid (CLA) preparations, which were enriched for the cis-9,trans-11 CLA isomer or the trans-10,cis-12 CLA isomer, on body composition in mice. Body composition changes (reduced body fat, enhanced body water, enhanced body protein, and enhanced body ash) were associated with feeding the trans-10,cis-12 CLA isomer. In cultured 3T3-L1 adipocytes, the trans-10,cis-12 isomer reduced lipoprotein lipase activity, intracellular triacylglycerol and glycerol, and enhanced glycerol release into the medium. By contrast, the cis-9,trans-11 and trans-9,trans-11 CLA isomers did not affect these biochemical activities. We conclude that CLA-associated body composition change results from feeding the trans-10,cis-12 isomer.

3T3 Cells↗

Changes in body composition in mice during feeding and withdrawal of conjugated linoleic acid.

Two experiments were conducted. In Experiment 1, 8-wk-old mice were fed control diet or diet supplemented with 0.5% conjugated linoleic acid (CLA) to study the effect of CLA on body composition (CLA: 40.8-41.1% c-9,t-11 isomer, 43.5-44.9% t-10,c-12 isomer). The data for CLA-fed mice vs. controls described parallel but significantly distinct responses for both absolute and relative changes in body fat mass (reduced in CLA-fed mice) and for relative changes in whole body protein and whole body water (both of which were increased in CLA-fed mice). In the CLA-fed mice, the effect on whole body protein appeared to precede the reduction in body fat mass. In Experiment 2, weanling mice were fed control diet or diet supplemented with 0.5% CLA for 4 wk (test group), at which time all mice were fed control diet devoid of added CLA. The test group exhibited significantly reduced body fat and significantly enhanced whole body water relative to controls at the time of diet change. Time trends for changes in relative body composition were described by parallel lines where the test group exhibited significantly less body fat but significantly more whole body protein, whole body water, and whole body ash than controls. Tissue CLA levels declined following the withdrawal of CLA from the diet. In skeletal muscle of mice fed CLA-supplemented diet, the t-10,c-12 isomer was cleared significantly faster than the c-9,t-11 CLA isomer.

Adipose Tissue↗

High-fat dairy product consumption increases delta 9c,11t-18:2 (rumenic acid) and total lipid concentrations of human milk.

Conjugated octadecadienoic acids (18:2, conjugated linoleic acids) have been shown to be anticarcinogenic and may influence growth and nutrient partitioning. The delta 9c,11t-18:2 isomer (rumenic acid, RA) is most common in both food sources and human tissues. To determine if maternal diet can influence milk RA concentration, breastfeeding women (n = 16) were enrolled in a 3-wk crossover study. Women initially consumed minimal amounts of food containing RA during week 1, then were assigned randomly to consume diets rich in high-fat dairy foods (and thus RA) during week 2 or 3. Milk was collected by complete breast expression twice during each experimental week. Current and chronic RA intakes were estimated by 3-d dietary records and food frequency questionnaires, respectively. Estimated chronic RA intakes ranged from 49 to 659 mg/d. Dietary RA intake was greater during the high compared to the low dairy period (291 +/- 75 vs. 15 +/- 24 mg/d, respectively; P < 0.0001). Milk contained more RA during the high than the low dairy period (13.5 +/- 0.1 vs. 8.2 +/- 0.4 mumol/g lipid, respectively; P < 0.0001). Milk lipid concentration was influenced by diet, such that lipid concentration was greater during the high than the low dairy period (46.6 +/- 5.0 vs. 38.3 +/- 1.6 mg/g milk, respectively; P < 0.05). Additionally, multiple regression analyses suggested that body mass index was the primary predictor of milk RA and lipid concentrations. In summary, these data indicate that both lipid and RA concentrations of human milk can be influenced by diet.

Adult↗

Resolution of chronic delta hepatitis after 12 years of interferon alfa therapy.

Chronic delta hepatitis is an uncommon but severe form of chronic viral hepatitis for which there is currently no satisfactory therapy. A patient with chronic delta hepatitis was treated with interferon alfa, 5 million units daily for 12 years. Serial serum samples were tested for routine liver tests and selected samples for quantitative levels of hepatitis B surface antigen (HBsAg) and hepatitis delta virus RNA. Liver biopsies were performed before, during, and after an initial 1-year course of therapy and again after 3 and 10 years of continuous therapy. With initiation of interferon therapy, serum aminotransferase levels decreased to normal range, became abnormal again when the dose was reduced, and increased to pretreatment levels when therapy was stopped. With reinstitution and prolonged therapy, aminotransferase levels became persistently normal; after several years, both hepatitis delta virus RNA and serum HBsAg became undetectable. Liver biopsy, which initially revealed cirrhosis, showed gradual improvement in inflammatory and fibrosis scores and, after 10 years, no abnormalities or fibrosis. Therapy was stopped, and the patient remained free of evidence of infection. In conclusion, long-term therapy with interferon alfa in high doses led to resolution of chronic delta hepatitis, disappearance of hepatitis delta and B virus markers, and improvement in fibrosis.

Adult↗

Development of wheezing in patients with cough variant asthma during an increase in airway responsiveness.

Two theories explaining the mechanism for the manifestation of cough without wheeze in patients with cough variant asthma (CVA) are either a higher wheezing threshold or a milder degree of airway hyperresponsiveness. A significant proportion of patients diagnosed as having CVA eventually develop wheezing. The aim of this study was to investigate whether this change in the manifestation of asthma was associated with a decrease in wheezing threshold and/or an increase in airway hyperresponsiveness. Thirty-six children (7-15 yrs) with CVA were prospectively studied for 4 yrs. Bronchial provocation tests with methacholine using the stepwise increasing concentration technique were performed annually to measure the provocative cumulative dose producing a 20% fall in forced expiratory volume in one second (PD20). Wheezing thresholds were additionally determined at the initiation of and the end of the study (development of wheezing, or after 4 yrs). Sixteen (Group 1) of 29 patients available for the follow-up developed clinical wheezing during the period; 13 patients (Group 2) stayed as CVA or their cough resolved. There was no significant change in wheezing thresholds from the initiation to the end of the study (Group 1: 40.9+/-8.2% versus 40.2+/-8.3%; Group 2: 41.4+/-7.1% versus 40.1+/-7.3%). Methacholine PD20 (geometric mean, range of 1 SD), expressed as breath unit (BU), significantly decreased in Group 1 patients as they developed wheezing (initial versus wheezing year: 60.8 BU, 29.2-126.5 versus 32.8 BU, 11.5-93.3; p<0.01), whereas the value did not change in Group 2 patients (initial versus after 4 yrs: 85.3 BU, 45.2-161.1 versus 84.3 BU, 39.7-179.1; NS). The results suggest that an increase in airway hyperresponsiveness, but not a decrease in wheezing threshold, may have a pathogenetic role in the development of wheezing during the course of cough variant asthma in childhood.

Adolescent↗

Voltage-gated sodium channel genes hscp and hDSC1 of Heliothis virescens F. genomic organization.

We report the genomic sequence of hscp, a sodium channel alpha subunit gene for Heliothis virescens. A 32-kb genomic clone and six independent RT-PCR products covering almost the entire coding region of the gene, contained thirty-one deduced exons with a translation of 1695 residues. Overall amino acid similarity to the para locus of Drosophila melanogaster was 86%. The transcription of the gene was complex. Alternate splicing was evident for five optional exons and a pair of mutually exclusive exons. A number of alternatively spliced mRNA revealed a deduced translation product that included only the first homology domain. We also report the first partial sequence for hDSC1, a presumed orthologous of the DSC1 sodium channel alpha subunit gene of D. melanogaster.

Alternative Splicing↗

Sleep patterns during 20-m nitrox saturation dives.

The sleep patterns were examined through three simulated 20-m nitrox saturation dives. The standard polysomnography of 12 divers was recorded respectively for a total of 204 nights, as were patterns of change or consistency in sleep variables. For the 11 divers in their 20s and 30s there was nothing unusual about their sleep variables. However, a reduction of total sleep time in accordance with the lengthening of sleep latency was observed. This was recognized from the latter part of the bottom period to the postdive period. This tendency was notable for the diver in his 50s. These findings suggest that the decompression environment and the psychological stress of the long-term closed environment of a hyperbaric chamber have effects on divers' sleep.

Adult↗

Fluorescence image analysis of the association between Porphyromonas gingivalis and gingival epithelial cells.

We have developed a fluorescence imaging technique using a DNA-binding dye to visualize, over time, the physical interactions between Porphyromonas gingivalis and human gingival epithelial cells in vitro. The results extend previous observations of P. gingivalis invasion of gingival epithelial cells based on indirect measurements. An intracellular location for P. gingivalis was established by optical sectioning of images in the z-plane. Kinetic analysis showed that P. gingivalis invasion of epithelial cells is a rapid and efficient process, reaching completion after 12 min. Imaging of infected monolayers revealed that over 90% of a population of gingival epithelial cells contained bacteria. Furthermore, only vital bacteria were capable of invasion, and intracellular bacteria congregated in the perinuclear region of the epithelial cells. P. gingivalis remained inside the epithelial cells over a 24 h period and induced rearrangement of the actin cytoskeleton along with alteration of the size and shape of the epithelial cells. These findings provide direct evidence that entry rates of P. gingivalis into gingival epithelial cells are high and rapid, and that internalized bacteria initially localize in a specific region of the epithelial cells.

Cell Nucleus↗

Characterization of antithrombotic activity of lumbrokinase-immobilized polyurethane valves in the total artificial heart.

Thirty ng/mm2 lumbrokinase, a potent fibrinolytic enzyme, was immobilized in a Korean type total artificial heart (KORTAH) valve by photoreaction; polyallylamine was used as a photoreactive linker. Lumbrokinase-immobilized polyurethane valves were then fitted to the total artificial hearts of 3 healthy 50 kg lambs. In the control lamb, the valves were untreated; in one other, only valves on the right were treated; and in the remaining animal, only those on the left. Implants were in place for up to 3 days, and cardiac output was 5 L/min. To facilitate thrombus formation, low doses of heparin were administered. In the control lamb, thrombi was observed only in the inlet parts of the valves. In the other 2 experiments, thrombi formed in untreated control valves but not in lumbrokinase treated valves. The grade of thrombus formation in untreated valves was 1.06+/-1.37 versus 0+/-0 in the treated part by one-sided Student's t-test (p < 0.1). After implantation, fibrinolytic activity was only observed in treated valves by fibrin plate methods. The proteolytic activity of the treated valves was 3 times higher than that of untreated valves using the azocasein method. These data show that lumbrokinase treated polyurethane valves lead to decreased thrombus formation in vivo and that their biocompatibility is therefore greater than that of untreated valves.

Animals↗

Isolation and characterization of a mutant defective in the production of methanol dehydrogenase from a new restricted facultative methanol-oxidizing bacterium.

A new restricted facultative methanol-oxidizing bacterium Methylobacillus sp. strain SK1 (DSM 8269) was subjected to insertion mutagenesis studies with the transposon Tn5 to generate mutants deficient in the production of methanol dehydrogenase (MDH). The transposon was conjugally transferred into the methylotroph by using the triparental mating procedure. The mutants induced by Tn5 were selected directly from a plate containing succinate by using the allyl alcohol selection procedure. The transposition of Tn5 to the bacterium showed a moderate transposition frequency (10(-5) - 10(-6)). Southern hybridization analysis confirmed that the transposon Tn5 was inserted into the chromosomal DNA of the mutants. In addition, the mutants had no RNA transcripts produced from the mdh gene, as judged by Northern blot analysis. The mutants could neither grow on methanol nor produce MDH protein, as determined by Western blot analysis with anti-MDH antibody. These results suggest that Tn5 mutagenesis maybe a useful tool for the molecular analysis of a facultative methanol-oxidizing bacterium.

Alcohol Oxidoreductases↗

Conjugated linoleic acid and the control of cancer and obesity.

The effects of conjugated linoleic acid (CLA) in animals are reviewed. In most of the CLA preparations that have been investigated to date for biological activity, two CLA isomers are present in about equal concentrations: cis-9,trans-11 CLA, and trans-10,cis-12 CLA. The occurrence of these isomers in foods and their production by rumen microorganisms are discussed. Potential mechanisms of action as regards the effects of CLA on cancer and body composition are reviewed, including recent evidence that body composition changes are produced by the trans-10,cis-12 CLA isomer. Evidence is presented indicating that CLA may modulate cellular response to tumor necrosis factor-alpha (TNF-alpha). The mechanistic implications of this finding are considered.

Animals↗

Identity of the universal repulsive-core singularity with Yang-Lee edge criticality.

Lattice and continuum fluid models with repulsive-core interactions typically display a dominant, critical-type singularity on the real, negative activity axis. Lai and Fisher recently suggested, mainly on numerical grounds, that this repulsive-core singularity is universal and in the same class as the Yang-Lee edge singularities, which arise above criticality at complex activities with positive real part. A general analytic demonstration of this identification is presented here using a field-theory approach with separate representations of the repulsive and attractive parts of the pair interactions.

Journal Article↗

Topology of RbsC, a membrane component of the ribose transporter, belonging to the AraH superfamily.

RbsC of Escherichia coli is the hydrophobic membrane component of ribose uptake system classified as the ATP-binding cassette transporter. To understand the structure and function of RbsC, its transmembrane topology was investigated by using 64 RbsC-PhoA fusions isolated either specifically or randomly. In order to confirm the cytoplasmic location of the short C-terminal region (5 amino acids), inside-out or right-side-out membrane vesicles were generated, and the C-terminal region was found to be digested by carboxypeptidase A only in inside-out vesicles. This result is consistent with the model, based on the results of alkaline phosphatase fusions, in which the protein traverses the membrane six times and the N and C termini are exposed to the cytoplasm.

ATP-Binding Cassette Transporters↗

Clinical efficacy of oxybutynin on sensory urgency as compared with that on motor urgency.

OBJECTIVE: Anticholinergic drug is widely accepted as an effective medication for frequency, urgency and urge incontinence related to detrusor overactivity (motor urgency). In order to elucidate whether anticholinergic drug is also effective for these symptoms related to bladder hypersensitivity (sensory urgency), clinical efficacy of oxybutynin on sensory urgency was compared with that on motor urgency. METHOD: Twenty-four patients with sensory urgency, and 53 patients with motor urgency were treated with oxybutynin (6 mg/day) for 4 weeks and subjective and objective efficacies were evaluated. Subjective parameters were quantified with urge score (grade 0-3) and daily numbers of voiding and incontinence. Objective efficacies were evaluated with pre-/ postcomparison of cystometric parameters. RESULTS: Excellent or good overall efficacy was obtained in 62.5% (15/24) of the sensory urgency group and 60.4% (32/53) of the motor urgency group. There was no statistical difference between these two groups. Objective cystometric parameters, bladder volume at first sensation and maximum cystometric capacity, statistically improved after the treatment in both groups. CONCLUSION: The results suggest that oxybutynin works as well on sensory urgency as it does on motor urgency.

Aged↗

Effect of Na-hyaluronan on stromal and endothelial healing in experimental corneal alkali wounds.

The healing of stroma and endothelium after a standardized corneal alkali wound was evaluated in sodium-hyaluronan (Na-HA)-treated eyes. Alkali wounds were produced in one eye of each rabbit by applying a 5.5-mm round filter paper soaked in 1 N NaOH onto the central cornea for 60 s. Eyes were then treated with either 1% Na-HA (the treatment group) or phosphate-buffered saline (the control group) 4 times per day for 3 weeks. Endothelial wound morphometry was performed after alizarin red and trypan blue staining, while stromal healing was assessed by counting polymorphonuclear leukocytes (PMNs) and keratocytes in the central and marginal wound areas. During the early healing period the stroma treated with Na-HA had less PMNs than that of the control group. The size of the endothelial defect area measured 5 days after injury was significantly smaller in the Na-HA group than in the control corneas. The present findings indicate that topically applied 1% Na-HA affects stromal and endothelial healing during the early repair process after corneal alkali wounds.

Alkalies↗

A fusion protein of the estrogen receptor (ER) and nuclear receptor corepressor (NCoR) strongly inhibits estrogen-dependent responses in breast cancer cells.

Nuclear receptor corepressor (NCoR) mediates repression (silencing) of basal gene transcription by nuclear receptors for thyroid hormone and retinoic acid. The goal of this study was to create novel estrogen receptor (ER) mutants by fusing transferable repressor domains from the N-terminal region of NCoR to a functional ER fragment. Three chimeric NCoR-ER proteins were created and shown to lack transcriptional activity. These fusion proteins silenced basal transcription of the ERE2-tk-Luc reporter gene and inhibited the activity of co-transfected wild-type ER (wtER), indicating that they possess dominant negative activity. One of the fusion proteins (CDE-RD1), containing the ER DNA-binding and ligand-binding domains linked to the NCoR repressor domain (RD1), was selected for detailed examination. Its hormone affinity, intracellular localization, and level of expression in transfected cells were similar to wtER, and it bound to the estrogen response element (ERE) DNA in gel shift assays. Glutathione-S-transferase pull-down assays showed that CDE-RD1 retains the ability to bind to steroid receptor coactivator-1. Introduction of a DNA-binding domain mutation into the CDE-RD1 fusion protein eliminated silencing and dominant negative activity. Thus, the RD1 repressor domain prevents transcriptional activation despite the apparent ability of CDE-RD1 to bind DNA, ligand, and coactivators. Transcriptional silencing was incompletely reversed by trichostatin A, suggesting a histone deacetylase-independent mechanism for repression. CDE-RD1 inhibited ER-mediated transcription in T47D and MDA-MB-231 breast cancer cells and repressed the growth of T47D cells when delivered to the cells by a retroviral vector. These ER-NCoR fusion proteins provide a novel means for inhibiting ER-mediated cellular responses, and analogous strategies could be used to create dominant negative mutants of other transcription factors.

Binding Sites↗

Altered properties of neuronal sodium channels associated with genetic resistance to pyrethroids.

Genetic resistance to pyrethroid insecticides involves nervous system insensitivity linked to regulatory and structural genes of voltage-sensitive sodium channels. We examined the properties and relative density of sodium channels in central neurons of susceptible and pyrethroid-resistant (Pyr-R) insects that were homozygous for the amino acid substitution V421M in the I-S6 transmembrane segment. Pyr-R sodium channels show approximately 21-fold lower sensitivity to the synthetic pyrethroid permethrin and a approximately 2-fold increased sensitivity to the alpha-scorpion toxin LqhalphaIT. Pyr-R channels also exhibit altered gating properties, including a approximately 13 mV positive shift in voltage-dependent activation and approximately 7 mV positive shift in steady-state inactivation. Consistent with these changes in gating behavior, Pyr-R central neurons are less excitable, as evidenced by an approximately 11 mV elevation of action potential threshold. No differences in sodium channel density are evident. The altered properties of Pyr-R sodium channels provide a plausible molecular basis for nervous system insensitivity associated with pyrethroid resistance.

Animals↗

Kinetics of thermal inactivation of penaeus penicillatus acid phosphatase

The kinetics of thermal inactivation of Penaeus penicillatus acid phosphatase have been studied using a kinetic method related to the substrate reaction during irreversible inhibition of the enzyme activity as previously described by Tsou (Adv. Enzymol. Relat. Areas Mol. Biol. (1988) 61, 381-436). The kinetics of thermal inactivation of the enzyme show that the reaction is irreversible. The microscopic rate constants were determined for thermal inactivation of free enzyme and the enzyme--substrate complex. The results show that the presence of substrate has a significant protective effect against thermal inactivation of the enzyme.

Journal Article↗