Biomedical subjects

E J Kim

Publications and source records attributed to E J Kim.

At least 37 records · Page 2Linked to original sources

PubMed2004

Bioequivalence of pravastatin tablet formulations assessed in Korean males.

AIM: Determination of the bioequivalence of 2 pravastatin tablet formulations manufactured in Korea. PATIENTS AND METHODS: Twenty-three healthy male Korean volunteers received each of the 2 pravastatin formulations at a dose of 20 mg in a 2 x 2 crossover study. There was a 1-week washout period between doses. Plasma concentrations of pravastatin were monitored using high-performance liquid chromatography over a period of 8 hours after administration. AUC(0-8h) (the area under the plasma concentration-time curve from time zero to the last measured time in plasma, 8 h) was calculated using the linear-log trapezoidal method. Cmax (maximum plasma drug concentration) and tmax (time to reach Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUC(0-8h) and Cmax and untransformed tmax. RESULTS: The point estimates and 90% confidence intervals for AUC(0-8h) (parametric) and Cmax (parametric) were 1.067 (0.968 to approximately 1.176) and 1.074 (0.999 to approximately 1.155), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines. The corresponding value of tmax was 0.000 (-0.250 to approximately 0.250). CONCLUSION: These results indicate that the 2 medications of pravastatin are bioequivalent and, thus, may be prescribed interchangeably.

Adult↗

PubMed2003

Transverse-momentum spectra in Au+Au and d+Au collisions at sqrt[s(NN)]=200 GeV and the pseudorapidity dependence of high-p(T) suppression.

We present spectra of charged hadrons from Au+Au and d+Au collisions at sqrt[s(NN)]=200 GeV measured with the BRAHMS experiment at RHIC. The spectra for different collision centralities are compared to spectra from p+(-)p collisions at the same energy scaled by the number of binary collisions. The resulting ratios (nuclear modification factors) for central Au+Au collisions at eta=0 and eta=2.2 evidence a strong suppression in the high p(T) region (>2 GeV/c). In contrast, the d+Au nuclear modification factor (at eta=0) exhibits an enhancement of the high p(T) yields. These measurements indicate a high energy loss of the high p(T) particles in the medium created in the central Au+Au collisions. The lack of suppression in d+Au collisions makes it unlikely that initial state effects can explain the suppression in the central Au+Au collisions.

Journal Article↗

PubMed2003

Rapidity dependence of charged antihadron to hadron ratios in Au+Au collisions at sqrt[s(NN)]=200 GeV.

We present ratios of the numbers of charged antihadrons to hadrons (pions, kaons, and protons) in Au+Au collisions at sqrt[s(NN)]=200 GeV as a function of rapidity in the range y=0-3. While the ratios at midrapidity are approaching unity, the K(-)/K(+) and p;/p ratios decrease significantly at forward rapidities. An interpretation of the results within the statistical model indicates a reduction of the baryon chemical potential from mu(B) approximately 130 MeV at y=3 to mu(B) approximately 25 MeV at y=0.

Journal Article↗

PubMed2003

Comparative bioavailability of silibinin in healthy male volunteers.

AIM: To study a comparative bioavailability of Liverman capsule to Legaion capsule and Silymarin tablet (which contain silibinin) in 24 healthy volunteers. VOLUNTEERS AND METHODS: Twenty-four healthy male Korean volunteers received each medicine at the silibinin dose of 120 mg in a 3 x 3 crossover study. There was a 1-week washout period among the doses. Plasma concentrations of silibinin were monitored by a high-performance liquid chromatography for over a period of 12 hours after the administration. AUCinf (the area under the plasma concentration-time curve from time zero to time infinity) was calculated by the trapezoidal rule extrapolation method. Cmax (maximum plasma drug concentration) and tmax (time to reach a Cmax) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed AUCinf, AUC(0-12h), and Cmax and untransformed tmax. RESULTS: After an oral administration of Liverman capsule, the pharmacokinetic parameters of silibinin, such as AUC(0-12h) (5.59, 4.24 and 13.9 microg/ml x h for Legalon capsule, Silymarin tablet and Liverman capsule, respectively) and AUCinf (6.00, 4.63 and 15.1 microg/ml x h) were significantly greater, Cmax (1.33, 1.13 and 6.04 microg/ml) was significantly higher and tmax (1.83, 2.10 and 0.875 h) was significantly faster than those after Legalon capsule and Silymarin tablet. CONCLUSION: These results indicate that the absorption and the extent of relative oral bioavailability of silibinin after Liverman capsule were significantly faster and greater, respectively, than those after Legalon capsule and Silymarin tablet.

Absorption↗

PubMed2002

Pseudorapidity distributions of charged particles from Au + Au collisions at the maximum RHIC energy, square root[s(NN)] = 200 GeV.

We present charged-particle multiplicities as a function of pseudorapidity and collision centrality for the 197Au+197Au reaction at square root[s(NN)] = 200 GeV. For the 5% most central events we obtain dN(ch)/deta/(eta = 0) = 625+/-55 and N(ch)/(-4.7< or =eta < or =4.7) = 4630 +/- 370, i.e., 14% and 21% increases, respectively, relative to square root[s(NN)] = 130 GeV collisions. Charged-particle production per pair of participant nucleons is found to increase from peripheral to central collisions around midrapidity. These results constrain current models of particle production at the highest RHIC energy.

Journal Article↗

PubMed2002

Dynamic characterization of recombinant Chinese hamster ovary cells containing an inducible c-fos promoter GFP expression system as a biomarker.

An inducible reporter gene system for Chinese Hamster Ovary (CHO-DHFR(-)) cells has been developed and characterized with respect to its dynamic properties. The reporter gene system consists of the human c-fos promoter and variants of the green fluorescence protein (GFP), either EGFP with enhanced fluorescence or its destabilized form d2EGFP. The expression of wild-type EGFP or its destabilized form was studied in CHO-DHFR(-) cells in response to serum addition or deprivation. It was shown that serum-induced c-fos promoter mediated EGFP expression was considerably higher than expression from the human CMV promoter, a strong, constitutive promoter preferentially used for high-level expression in CHO cells. However, EGFP was less suitable for studying expression dynamics than d2EGFP due to the protein's long half-life in mammalian cells. The use of d2EGFP resulted in a significant improvement in the dynamic characteristics of the biomarker, particularly when the recombinant cells were selected for high-level GFP expression by subcloning or fluorescence activated cell/sorting (FACS). GFP expression in different subclones and cell populations sorted by FACS was characterized with respect to its dynamic responses in the presence or absence of serum in the culture medium. Significant differences in the GFP expression dynamics were observed for the isolated cell populations. The experimental results indicate that cells with high-level GFP expression also have a faster dynamic response and are thus, desirable for practical application of the reporter gene system e.g. in toxicity monitoring.

Animals↗

PubMed2002

Evaluation of endoscopic hemostasis in upper gastrointestinal bleeding related to Mallory-Weiss syndrome.

BACKGROUND AND STUDY AIMS: The endoscopic hemostatic method has been introduced as a safe and effective mechanical approach to hemostasis for upper gastrointestinal bleeding related to Mallory-Weiss syndrome (MWS). However, the indications for when to use endoscopic treatment are debatable because many patients need only medical observation. The study was designed to evaluate the necessity and efficacy of endoscopic hemostasis in upper gastrointestinal bleeding related to MWS. PATIENTS AND METHODS: From July 1994 to May 2000, we conducted a clinical trial in 76 patients who were found by endoscopy to have active bleeding (I, spurting; II, oozing), protruding visible vessels (III), and/or adherent clots (IV). Two study periods can be differentiated: in the first 3 years endoscopic treatment (n = 30) was prospectively analyzed and in the final 3 years medical treatment (n = 46) was analyzed in both cases to compare the outcome in MWS bleeding II-IV. In the first study period, in addition, endoscopic treatment was randomised to an injection method, using a mixture of hypertonic saline and epinephrine (HSE) (n = 14) and a hemoclipping or band ligation method (n = 16). RESULTS: Rebleeding was observed in four of 14 patients who had received endoscopic hemostasis with HSE injection and one of 46 patients who had been managed with medical treatment. No rebleeding was found following hemoclipping or band ligation. While all rebleeding was in bleeding stigmata of the I (1) and II (4) grades, there was no rebleeding in protruding visible vessels (III) or in adherent clots (IV), regardless of treatment methods. CONCLUSIONS: Our results suggested that endoscopic hemostasis is not necessary in patients without active bleeding stigmata, and the mechanical hemostatic method is more effective than HSE injection in patients with active bleeding stigmata.

Adult↗

PubMed2002

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↗

PubMed2001

Antiproliferative mechanism of retinoid derivatives in ovarian cancer cells.

Retinoid derivatives have been implicated for the growth regulation of ovarian cancer cells. However, the molecular mechanisms are not yet fully defined. To dissect detailed mechanisms of each derivative, four ovarian cancer cells (A2774, PA-1, OVCAR-3, SKOV-3) were treated with all-trans retinoic acid (ATRA), 9-cis retinoic acid (9-cis RA), 13-cis RA, or 4-hydroxyphenyl retinamide (4-HPR). When treated with 1 microm, HPR inhibits most effectively the growth of all four cells. Depending on cell types treated, IC(50) values were 0.7-2.7 microm for 4-HPR, and 2.7-9.0 microm for other retinoid derivatives. DNA fragmentation assay indicated that the antiproliferative effect of HPR could be mediated by apoptosis. Transcription assays coupled with transient transfection in OVCAR-3 cells indicated that ATRA, 9-cis RA, and 13-cis RA were active for all RAR/RXR subtypes, whereas 4-HPR was only active for RARgamma. However, 4-HPR exerted the strongest suppression on AP-1 (c-Jun) activity. As expected from AP-1 data, in vitro invasion assays showed that HPR blocked effectively the migration of OVCAR-3 cells. Thus, 4-HPR showed not only more potent antiproliferative activity than any other retinoid derivatives used, but also effectively inhibited the invasion, probably through the suppression of AP-1 activity. Taken together coupled with its selective activity only for RARgamma, these results suggest that 4-HPR could be less toxic, and very effective anticancer drugs for late stage ovarian cancer.

Anticarcinogenic Agents↗

PubMed2001

Antilambda production in Au+Au collisions at 11.7A GeV/c.

We present results for antilambda and antiproton production in Au+Au collisions at 11.7 A GeV/c including spectra and extracted invariant yields for both species in central and peripheral collisions in the rapidity range 1.0<y<1.4. The antilambda yield increases from dN(Lambda;)/dy = 1.2(+0.7+0.2)(-0.6-0.2)x10(-3) in peripheral collisions to 19(+4+3)(-5-2)x10(-3) in central collisions. The direct antiproton yield is deduced from the measured total antiproton spectra to extract the ratio of antilambda-to-direct-antiproton production. The Lambda/p ratio near midrapidity increases from 0.26(+0.19+0.5)(-0.15-0.4) in peripheral collisions to 3.6(+4.7+2.7)(-1.8-1.1) in central collisions, a value larger than current theoretical estimates.

Journal Article↗

PubMed2001

Interleukin-2 fusion protein with anti-CD3 single-chain Fv (sFv) selectively protects T cells from dexamethasone-induced apoptosis.

Apoptosis of mature T cells may be an important pathophysiologic mechanism in diseases such as AIDS, cancer, and autoimmunity. In this study, in order to selectively protect T cells from dexamethasone (DEX)-induced apoptosis we constructed a fusion protein (anti-CD3sFv-IL-2) in which anti-CD3 single-chain Fv (sFv), the smallest unit of antibody recognizing the CD3 epsilon moiety of the T-cell receptor (TCR), was covalently linked to murine interleukin-2 (IL-2). Recombinant anti-CD3sFv protein was also expressed and used as a control. The purified anti-CD3sFv-IL-2 protein displayed IL-2 bioactivity in an IL-2 proliferation assay, which was inhibited by a neutralizing mIL-2 mAb. The anti-CD3sFv-IL-2 protein protected T lymphoma cells (S49.1) from DEX-induced apoptosis as demonstrated by oligonucleosomal genomic DNA fragmentation assay, and also recovered proliferation capacity of DEX-treated S49.1 cells and increased T cell composition both in DEX-treated spleen cell-populations and in DEX-treated mice, while the anti-CD3sFv protein did not. In addition, the anti-CD3sFv-IL-2 fusion protein was more efficient than a simple mixture of anti-CD3sFv and free rIL-2 in selectively protecting T cells from DEX-induced apoptosis. The levels of bcl-2 gene expression were significantly increased in DEX-treated T cells in the presence of the anti-CD3sFv-IL-2 protein. These studies indicate that the anti-CD3sFv-IL-2 fusion protein can selectively protect T cells from DEX-induced apoptosis and that the covalent linkage of anti-CD3sFv and IL-2 confines the anti-apoptotic effect of IL-2 to T cells.

Animals↗

PubMed2001

Synthetic low-calcaemic vitamin D(3) analogues inhibit secretion of insulin-like growth factor II and stimulate production of insulin-like growth factor-binding protein-6 in conjunction with growth suppression of HT-29 colon cancer cells.

The aims of the present study were to compare the ability of various synthetic analogues of 1 alpha,25-dihydroxyvitamin D(3) [1 alpha,25-(OH)(2)D(3)] to inhibit proliferation of HT-29 cells, a human colon adenocarcinoma cell line. HT-29 cells were incubated for 144 h with various concentrations (0-100 nM) of 1 alpha,25-(OH)(2)D(3), or the analogues EB1089, CB1093 or 1 beta,25-(OH)(2)D(3). All these analogues except 1 beta,25-(OH)(2)D(3) inhibited cell proliferation, but relative potencies and efficacies of EB1089 and CB1093 were much greater than that of the native vitamin. Cells grew in serum-free medium, reaching a plateau density at day 10 of culture, and addition of 10 nM 1 alpha,25-(OH)(2)D(3) or 1 beta,25-(OH)(2)D(3) did not alter the long-term growth characteristics of HT-29 cells. However, cells treated with 10 nM EB1089 or CB1093 grew at a rate slower than control and reached final densities that were 53+/-1 and 36+/-2% lower than control, respectively. Immunoblot analysis of serum-free conditioned medium using a monoclonal anti-insulin-like growth factor-(IGF)-II antibody showed that both 10 nM EB1089 and CB1093 markedly inhibited secretion of both mature 7500 M(r) and higher M(r) forms of IGF-II. Ligand blot and immunoblot analyses of conditioned media revealed the presence of IGFBPs of M(r) 24,000 (IGFBP-4), 30,000 (glycosylated IGFBP-4), 35,000 (IGFBP-2) and 32,000-34,000 (IGFBP-6). The level of IGFBP-2 was decreased by 42+/-8 and 49+/-7% by 10 nM EB 1089 and CB1093, respectively, compared to controls. IGFBP-6 was increased approximately twofold by EB1089 and CB1093, and exogenously added IGFBP-6 inhibited HT-29 cell proliferation. These results suggest that inhibition of HT-29 cell proliferation by EB1089 and CB1093 may be attributed, at least in part, to the decreased secretion of IGF-II. The increase in IGFBP-6 concentration coupled with its high affinity for IGF-II may also contribute to decreased cellular proliferation by an indirect mechanism involving sequestration of endogenously produced IGF-II.

Animals↗

PubMed2001

Mechanistic insight into the inactivation of carboxypeptidase A by alpha-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid, a novel type of irreversible inhibitor for carboxypeptidase A with no stereospecificity.

On the basis of the active site topology and enzymic catalytic mechanism of carboxypeptidase A (CPA), a prototypical zinc-containing proteolytic enzyme, alpha-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid (1), was designed as a novel type of mechanism-based inactivator of the enzyme. All four possible stereoisomers of the inhibitor were synthesized in an enantiomerically pure form starting with optically active aspartic acid, and their CPA inhibitory activities were evaluated to find that surprisingly all of the four stereoisomers inhibit CPA in a time dependent manner. The inhibited enzyme did not regain its enzymic activity upon dialysis. The inactivations were prevented by 2-benzylsuccinic acid, a competitive inhibitor that is known to bind the active site of the enzyme. These kinetic results strongly support that the inactivators attach covalently to the enzyme at the active site. The analysis of ESI mass spectral data of the inactivated CPA ascertained the conclusion from the kinetic results. The values of second-order inhibitory rate constants (k(obs)/[I](o)) fall in the range of 1.7-3.6 M(-1) min(-1). The lack of stereospecificity shown in the inactivation led us to propose that the ring cleavage occurs by the nucleophilic attack at the 2-position rather than at the 5-position and the ring opening takes place in an addition-elimination mechanism. The tetrahedral transition state that would be generated in this pathway is thought to be stabilized by the active site zinc ion, which was supported by the PM3 semiemprical calculations. In addition, alpha-benzyl-2-oxo-1,3-oxazolidine-5-acetic acid (18), a structural isomer of 1 was also found to inactivate CPA in an irreversible manner, reinforcing the nucleophilic addition-elimination mechanism. The present study demonstrates that the transition state for the inactivation pathway plays a critical role in determining stereochemistry of the inactivation.

Carboxypeptidases↗

PubMed2001

Rapidity dependence of antiproton-to-proton ratios in Au+Au collisions at square root of (sNN) = 130 GeV.

Measurements, with the BRAHMS detector, of the antiproton-to-proton ratio at midrapidities and forward rapidities, are presented for Au+Au reactions at square root of [s(NN)] = 130 GeV, and for three different collision centralities. For collisions in the 0%-40% centrality range, we find N(&pmacr;)/N(p) = 0.64+/-0.04((stat))+/-0.06((syst)) at y approximately 0, 0.66+/-0.03+/-0.06 at y approximately 0.7, and 0.41+/-0.04+/-0.06 at y approximately 2. The ratios are found to be nearly independent of collision centrality and transverse momentum. The antiproton and proton rapidity densities vary differently with rapidity, and indicate a significant degree of collision transparency, although a net-baryon free midrapidity plateau (Bjorken limit) is not yet reached.

Journal Article↗

PubMed2001

Differential roles of cyclooxygenase isoforms after kainic acid-induced prostaglandin E(2) production and neurodegeneration in cortical and hippocampal cell cultures.

Prostaglandins, which are cyclooxygenase (COX) products, are pathologically up-regulated, and have been proven to be closely associated with neuronal death. In this study, we investigated a role of COX isoforms (COX-1 and COX-2) in kainic acid-induced neuronal death in cultured murine cortical or hippocampal neurons. In primary cortical neurons, both indomethacin (COX-1/-2 nonselective inhibitor) and aspirin (COX-1 preferential inhibitor) reduced basal and kainic acid-induced PGE(2) production significantly and prevented neuronal cell death after kainic acid treatment. In contrast, NS398 (COX-2 selective inhibitor) had no effect on kainic acid-induced neuronal cell death. In hippocampal neurons, however, COX-2 inhibitors prevented both kainic acid-induced neuronal death and PGE(2) production. COX-2 expression was remarkably up-regulated by kainic acid in hippocampal neurons; whereas in cortical neurons, COX-2 expression was comparatively less significant. Astrocytes were unresponsive to kainic acid in terms of PGE(2) production and cell death. In conclusion, we suggest that the release of PGE(2) induced by kainic acid occurred through COX-1 activity rather than COX-2 in cortical neurons. The inhibition of PGE(2) release by COX-1 inhibitors prevented kainic acid-induced cortical neuronal death, while in the hippocampal neurons, COX-2 inhibitors prevented kainic acid-induced PGE(2) release and hippocampal neuronal death.

Animals↗

PubMed2001

Isolation and characterization of an apoptosis-inhibiting component from the hemolymph of Bombyx mori.

Silkworm (Bombyx mori) hemolymph showed an apoptosis-inhibiting activity in insect cells (Sf 9) infected with baculovirus (AcNPV). The addition of silkworm hemolymph into the culture medium increased the host cell longevity due to its apoptosis-inhibition activity. Components with an apoptosis-inhibiting effect were purified from the silkworm hemolymph by heat treatment, gel-filtration chromatography, and ion-exchange chromatography. The component with highest activity was characterized by periodic acid-Schiff staining, isoelectric focusing, MALDI-TOF-mass spectrometry, and N-terminal sequencing and was found to be a nonglycosylated monomeric protein with a molecular weight of ca. 28,000 Da.

Amino Acid Sequence↗

PubMed2001

Suppression by a sesquiterpene lactone from Carpesium divaricatum of inducible nitric oxide synthase by inhibiting nuclear factor-kappaB activation.

Excessive nitric oxide (NO) produced by inducible NO synthase (iNOS) acts as a causative regulator in various inflammatory disease states. Carpesium divaricatum has been used in Korean traditional herbal medicine for its antipyretic, analgesic, vermifugic, and anti-inflammatory properties. We investigated the molecular mechanism for the suppression of lipopolysaccharide/interferon-gamma (LPS/IFN-gamma)-induced NO production in RAW 264.7 macrophages by the sesquiterpene lactone 2beta,5-epoxy-5,10-dihydroxy-6alpha-angeloyloxy-9beta-isobutyloxy-germacran-8alpha,12-olide (C-1), which has been identified recently as a new compound from C. divaricatum. C-1 decreased NO production in LPS/IFN-gamma-stimulated RAW 264.7 cells in a concentration-dependent manner, with an IC50 of approximately 2.16 microM; however, it had no direct effect on the iNOS activity of fully LPS/IFN-gamma-stimulated RAW 264.7 cells. Furthermore, treatment with C-1 led to a decrease in iNOS protein and mRNA. These effects appear to be due to inhibition of nuclear factor-kappaB (NF-kappaB) activation through a mechanism involving stabilization of the NF-kappaB/inhibitor of the kappaB (I-kappaB) complex, since inhibition of NF-kappaB DNA binding activity by C-1 was accompanied by a parallel reduction of nuclear translocation of subunit p65 of NF-kappaB and I-kappaBalpha degradation. Taken together, the results suggest that the ability of C-1 to inhibit iNOS gene expression may be responsible, in part, for its anti-inflammatory effects.

Animals↗

PubMed2001

Functional inactivation of p73, a homolog of p53 tumor suppressor protein, by human papillomavirus E6 proteins.

Human papillomavirus (HPV) is strongly implicated as a causative agent in the etiology of cervical cancer. Of its gene products, E6 binds to and inactivates p53 tumor suppressor protein by ubiquitin/proteasome-dependent degradation. Recently, p73, a novel family of p53, has been identified and demonstrated, like p53, to activate p21(WAF1). Here we show that p73 is also inactivated by HPV-E6, but ubiquitin-mediated proteolysis is not responsive. Yeast two-hybrid and GST pull-down assays indicate a physical interaction between p73 and either HPV-16 or HPV-11 E6 proteins in vivo and in vitro, respectively. The transactivation domain (amino acid residues 1 to 49) is found to be absolutely required for the interaction. Transient co-expression of E6 significantly inhibits the p73-mdiated activation of p21(WAF1) promoter in a p53-defective C33A cell line. Using Gal4-p73 fusion protein, we demonstrate that E6 inhibition of p73 transactivation function is independent of sequence-specific DNA binding, which is confirmed by a direct electrophoretic mobility shift assay. Moreover, E6 inhibits p73 function by interfering with the activity of the amino-terminal activation domain. Co-transfection of E6 mutants reveals that the same portion of E6 appears to be responsible for the inactivation of p53 and p73 function. However, the inactivation mechanism of p73 is clearly different from that of p53, because p73, unlike p53, is inactivated by both high- and low-risk E6s and is not susceptible to E6-dependent proteolysis. These overall results, consequently, suggest that in addition to the inactivation of p53, the functional interference of p73 by HPV-E6 may, at least in part, contribute to E6-mediated transformation and hyperproliferation of cervical cells.

Apoptosis↗