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Biomedical subjects

K Y Choi

Publications and source records attributed to K Y Choi.

At least 19 recordsLinked to original sources

Degradation of atrazine by modified stepwise-Fenton's processes.

The removal of atrazine (ATZ) by stepwise Fenton's processes (stepwise-FP) was studied and the system models were developed through the examination of reaction kinetics. The study compared the performance of the removal of ATZ by conventional FP with stepwise-FP, where the total dose of H(2)O(2) was split and inputted into the system at different times and/or quantities. The performance of stepwise-FP was found to be better than that of conventional FP. This was probably due to the minimization of the peak concentration of H(2)O(2) in the solution, which reduced the probability that valuable H(2)O(2) and hydroxyl radicals would be consumed in forming weaker radicals. The reaction kinetics of the decay of ATZ in stepwise-FP was found to be a two-stage process; and in each stage, fast decay followed by stagnant decay was observed. Two characterized constants (the initial decay rate and the oxidative capacity) were introduced and were found to be useful in quantifying the stepwise-FP. The models for predicting stepwise-FP with respect to different dosing times and/or asymmetrical doses were developed, and were found to be very useful for evaluating the system performance and/or for process design.

Atrazine↗

Anomalous electronic Raman scattering in NaxCoO2.yH2O.

Raman scattering experiments on NaxCoO2.yH2O single crystals show a broad electronic continuum with a pronounced peak around 100 cm(-1) and a cutoff at approximately 560 cm(-1) over a wide range of doping levels. The electronic Raman spectra in superconducting and nonsuperconducting samples are similar at room temperature, but evolve in markedly different ways with decreasing temperature. For superconducting samples, the low-energy spectral weight is depleted upon cooling below T* approximately 150 K, indicating the opening of a pseudogap that is not present in nonsuperconducting materials. Weak additional phonon modes observed below T* suggest that the pseudogap is associated with charge ordering.

Journal Article↗

Serotonin transporter gene polymorphism and irritable bowel syndrome.

Polymorphisms in the promoter region of the serotonin reuptake transporter (SERT) gene may underlie the disturbance in gut function in patients with irritable bowel syndrome (IBS). Association studies of SERT polymorphisms and IBS have shown diverse results among different countries, which might be due to racial and subject composition differences. The aim of this study was to assess the potential association between SERT polymorphisms and IBS in Koreans. A total of 190 IBS patients, who met the Rome II criteria, and 437 healthy controls were subjected to genotyping. SERT polymorphisms differed in the IBS and control groups (P = 0.014). The SERT deletion/deletion genotype occurred with greater frequency in the diarrhoea-predominant IBS group than in the controls. A strong genotypic association was observed between the SERT deletion/deletion genotype and diarrhoea-predominant IBS (P = 0.012). None of the clinical symptoms analysed was significantly associated with the SERT genotypes. The frequency of the SERT insertion/insertion genotype was much lower than that of the other two genotypes. A significant association was observed between the SERT polymorphism and IBS, especially diarrhoea-predominant IBS, suggesting that the SERT gene is a potential candidate gene involved in IBS in Korea.

Adult↗

Primary colon lymphoma in Korea: a KASID (Korean Association for the Study of Intestinal Diseases) Study.

Although almost all primary colorectal lymphomas are of B-cell lineage in Western countries, primary colorectal T-cell lymphomas are not uncommon in the East. The aim of this study was to review the clinical characteristics and treatment outcomes of primary colorectal lymphomas, with special emphasis on the differences between T-cell and B-cell lymphomas. Ninety-five cases of primary colorectal lymphomas that satisfied Dawson's criteria were identified from the clinical databases of 13 university hospitals in Korea. The mean age at the time of presentation was 51.1 years and the male:female ratio was 64:31. The clinical information, including endoscopic and histological characteristics, was retrospectively analyzed. Of the primary colorectal lymphomas, 78 cases (82.1%) were of B-lineage and 17 cases (17.9%) were of T-cell lineage. Patients with T-cell lymphomas presented at a younger age than patients with B-cell lymphomas (42.8 vs 52.9 years, respectively; P = 0.016). The most common presenting symptom was abdominal pain (87.1%) for B-cell lymphomas, whereas hematochezia or night fever was more common for T-cell lymphomas (52.9% and 35.3%, respectively). The most common endoscopic type was fungating mass (54.0%) for B-cell lymphomas and ulcerative/ulcero-infiltrative lesions (80.0%) for T-cell lymphomas. Intussusception was more common in B-cell lymphomas than in T-cell lymphomas (30.8% vs 5.9%, respectively; P = 0.035), but perforation was more common in T-cell lymphomas than in B-cell lymphomas (23.5% vs 3.8%, respectively; P = 0.005). The prognosis was significantly worse for T-cell lymphomas than for B-cell lymphomas (P = 0.002). Primary colorectal T-cell lymphomas are characterized by multifocal ulcerative lesions in relatively young patients, a high rate of hematochezia, fever, or perforation, and a poor prognosis even for cases of localized disease.

Adolescent↗

Endoscopic hemoclipping using a transparent cap in technically difficult cases.

BACKGROUND AND STUDY AIMS: Technical difficulties have been experienced in endoscopic hemoclipping on the posterior wall of the body of the stomach because the angle of approach is tangential. It has been suggested that the use of a transparent cap on the tip of the endoscope could help to solve this problem. The purpose of this study was to examine the efficacy of endoscopic hemoclipping using a transparent cap over the tip of the endoscope. PATIENTS AND METHODS: A total of 74 patients with a bleeding peptic ulcer or stigmata of recent hemorrhage underwent endoscopic hemoclipping. Technical difficulty in hemoclipping was experienced in 18 patients and the transparent cap was used in these cases. We therefore conducted a nonrandomized prospective study to compare bleeding control with the hemoclip with and without the aid of a transparent cap. RESULTS: There were no statistically significant differences between the patients treated with the cap and those treated without the cap with regard to the initial hemostasis rate (94.4 % vs. 91.1 %), the rebleeding rate (11.7 % vs. 11.8 %), or the permanent hemostasis rate (94.4 % vs. 96.4 %). CONCLUSIONS: Although there was no statistically significant difference between patients treated with or without a transparent cap, hemoclipping with the aid of the cap made it possible to clip a lesion too tangential to be clipped without it. However, this study did not compare conventional hemoclipping with hemoclipping using a cap because the cap was only used in cases in which conventional clipping had failed.

Duodenal Ulcer↗

Two cases of steakhouse syndrome associated with nutcracker esophagus.

The most common type of esophageal food-related foreign body is the meat bolus, which is frequently associated with underlying esophageal stenosis. Herein, we report two cases of meat bolus impaction associated with nutcracker esophagus. In the first case, the 63-year-old male patient had chest discomfort and swallowing difficulty after ingestion of butcher's meat. In the second case, the 55-year-old male patient had complained of swallowing difficulty after ingestion of chicken. In both cases, no pathologic findings were observed endoscopically after removal of the esophageal meat bolus. We performed esophageal manometry, which showed very high amplitudes of esophageal pressure in the mid- and distal esophagus. These findings were consistent with nutcracker esophagus. These cases show that esophageal motility disorder may be the cause of esophageal foreign body impaction, and esophageal manometry should be performed for evaluation of the cause of foreign body, especially in an endoscopically normal patient.

Deglutition Disorders↗

Maintenance of alpha-helical structures by phenyl rings in the active-site tyrosine triad contributes to catalysis and stability of ketosteroid isomerase from Pseudomonas putida biotype B.

Ketosteroid isomerase (KSI) from Pseudomonas putida biotype B is a homodimeric enzyme catalyzing an allylic rearrangement of Delta5-3-ketosteroids at rates comparable with the diffusion-controlled limit. The tyrosine triad (Tyr14.Tyr55.Tyr30) forming a hydrogen-bond network in the apolar active site of KSI has been characterized in an effort to identify the roles of the phenyl rings in catalysis, stability, and unfolding of the enzyme. The replacement of Tyr14, a catalytic residue, with serine resulted in a 33-fold decrease of kcat, while the replacements of Tyr30 and Tyr55 with serine decreased kcat by 4- and 51-fold, respectively. The large decrease of kcat for Y55S could be due to the structural perturbation of alpha-helix A3, which results in the reorientation of the active-site residues as judged by the crystal structure of Y55S determined at 2.2 A resolution. Consistent with the analysis of the Y55S crystal structure, the far-UV circular dichroism spectra of Y14S, Y30S, and Y55S indicated that the elimination of the phenyl ring of the tyrosine reduced significantly the content of alpha-helices. Urea-induced equilibrium unfolding experiments revealed that the DeltaG(U)H2O values of Y14S, Y30S, and Y55S were significantly decreased by 11.9, 13.7, and 9.5 kcal/mol, respectively, as compared with that of the wild type. A characterization of the unfolding kinetics based on PhiU-value analysis indicates that the interactions mediated by the tyrosine triad in the native state are very resistant to unfolding. Taken together, our results demonstrate that the internal packing by the phenyl rings in the active-site tyrosine triad contributes to the conformational stability and catalytic activity of KSI by maintaining the structural integrity of the alpha-helices.

Amino Acid Substitution↗

Evidence for an unconventional magnetic instability in the spin-tetrahedra system Cu(2)Te(2)O(5)Br(2).

Thermodynamic experiments as well as Raman scattering have been used to study the magnetic instabilities in the spin-tetrahedra systems Cu(2)Te(2)O(5)X(2), X = Cl and Br. While the phase transition observed in the Cl system at T(N) = 18.2 K is consistent with 3D antiferromagnetic ordering, the phase transition at T(o) = 11.4 K in the Br system has several unusual features. We propose an explanation in terms of weakly coupled tetrahedra with a singlet-triplet gap and low-lying singlets.

Journal Article↗

The role of Tyr248 probed by mutant bovine carboxypeptidase A: insight into the catalytic mechanism of carboxypeptidase A.

We have investigated the function of Tyr248 using bovine wild-type CPA and its Y248F and Y248A mutants to find that the K(M) values were increased by 4.5-11-fold and the k(cat) values were reduced by 4.5-10.7-fold by the replacement of Tyr248 with Phe for the hydrolysis of hippuryl-L-Phe (HPA) and N-[3-(2-furyl)acryloyl]-Phe-Phe (FAPP), respectively. In the case of O-(trans-p-chlorocinnamoyl)-L-beta-phenyllactate (ClCPL), an ester substrate, the K(M) value was increased by 2.5-fold, and the k(cat) was reduced by 20-fold. The replacement of Tyr248 with Ala decreased the k(cat) values by about 18- and 237-fold for HPA and ClCPL, respectively, demonstrating that the aromatic ring of Tyr248 plays a critical role in the enzymic reaction. The increases of the K(M) values were only 6- and 5-fold for HPA and ClCPL, respectively. Thus, the present study indicates clearly that Tyr248 plays an important role not only in the binding of substrate but also in the enzymic hydrolysis. The kinetic results may be rationalized by the proposition that the phenolic hydroxyl of Tyr248 forms a hydrogen bond with the zinc-bound water molecule, causing further activation of the water molecule by reducing its pK(a) value. The pH dependency study of k(cat) values and the solvent isotope effects also support the proposition. A unified catalytic mechanism is proposed that can account for the different kinetic behavior observed in the CPA-catalyzed hydrolysis of peptide and ester substrates.

Amino Acid Sequence↗

Pseudoreversion of the catalytic activity of Y14F by the additional substitution(s) of tyrosine with phenylalanine in the hydrogen bond network of delta 5-3-ketosteroid isomerase from Pseudomonas putida biotype B.

Delta5-3-ketosteroid isomerase (KSI) from Pseudomonas putida Biotype B catalyzes the allylic isomerization of Delta5-3-ketosteroids to their conjugated Delta4-isomers via a dienolate intermediate. Two electrophilic catalysts, Tyr-14 and Asp-99, are involved in a hydrogen bond network that comprises Asp-99 Odelta2...O of Wat504...Tyr-14 Oeta...Tyr-55 Oeta.Tyr-30 Oeta in the active site of P. putida KSI. Even though neither Tyr-30 nor Tyr-55 plays an essential role in catalysis by the KSI, the catalytic activity of Y14F could be increased ca. 26-51-fold by the additional Y30F and/or Y55F mutation in the hydrogen bond network. To identify the structural basis for the pseudoreversion in the KSI, crystal structures of Y14F and Y14F/Y30F/Y55F have been determined at 1.8 and 2.0 A resolution, respectively. Comparisons of the two structures near the catalytic center indicate that the hydrogen bond between Asp-99 Odelta2 and C3-O of the steroid, which is perturbed by the Y14F mutation, can be partially restored to that in the wild-type enzyme by the additional Y30F/Y55F mutations. The kinetic parameters of the tyrosine mutants with the additional D99N or D99L mutation also support the idea that Asp-99 contributes to catalysis more efficiently in Y14F/Y30F/Y55F than in Y14F. In contrast to the catalytic mechanism of Y14F, the C4 proton of the steroid substrate was found to be transferred to the C6 position in Y14F/Y30F/Y55F with little exchange of the substrate 4beta-proton with a solvent deuterium based on the reaction rate in D2O. Taken together, our findings strongly suggest that the improvement in the catalytic activity of Y14F by the additional Y30F/Y55F mutations is due to the changes in the structural integrity at the catalytic site and the resulting restoration of the proton-transfer mechanism in Y14F/Y30F/Y55F.

Acrylamide↗

Folding mechanism of ketosteroid isomerase from Comamonas testosteroni.

Ketosteroid isomerase (KSI) from Comamonas testosteroni is a homodimeric enzyme with 125 amino acids in each monomer catalyzing the allylic isomerization reaction at rates comparable to the diffusion limit. Kinetic analysis of KSI refolding has been carried out to understand its folding mechanism. The refolding process as monitored by fluorescence change revealed that the process consists of three steps with a unimolecular fast, a bimolecular intermediate, and most likely unimolecular slow phases. The fast refolding step might involve the formation of structured monomers with hydrophobic surfaces that seem to have a high binding capacity for the amphipathic dye 8-anilino-1-naphthalenesulfonate. During the refolding process, KSI also generated a state that can bind equilenin, a reaction intermediate analogue, at a very early stage. These observations suggest that the KSI folding might be driven by the formation of the apolar active-site cavity while exposing hydrophobic surfaces. Since the monomeric folding intermediate may contain more than 83% of the native secondary structures as revealed previously, it is nativelike taking on most of the properties of the native protein. Urea-dependence analysis of refolding revealed the existence of folding intermediates for both the intermediate and slow steps. These steps were accelerated by cyclophilin A, a prolyl isomerase, suggesting the involvement of a cis-trans isomerization as a rate-limiting step. Taken together, we suggest that KSI folds into a monomeric intermediate, which has nativelike secondary structure, an apolar active site, and exposed hydrophobic surface, followed by dimerization and prolyl isomerizations to complete the folding.

Aldose-Ketose Isomerases↗

15N NMR relaxation studies of backbone dynamics in free and steroid-bound Delta 5-3-ketosteroid isomerase from Pseudomonas testosteroni.

The backbone dynamics of Delta(5)-3-ketosteroid isomerase (KSI) from Pseudomonas testosteroni has been studied in free enzyme and its complex with a steroid ligand, 19-nortestosterone hemisuccinate (19-NTHS), by (15)N relaxation measurements. The relaxation data were analyzed using the model-free formalism to extract the model-free parameters (S(2), tau(e), and R(ex)) and the overall rotational correlation time (tau(m)). The rotational correlation times were 19.23 +/- 0.08 and 17.08 +/- 0.07 ns with the diffusion anisotropies (D( parallel)/D( perpendicular)) of 1.26 +/- 0.03 and 1.25 +/- 0.03 for the free and steroid-bound KSI, respectively. The binding of 19-NTHS to free KSI causes a slight increase in the order parameters (S(2)) for a number of residues, which are located mainly in helix A1 and strand B4. However, the majority of the residues exhibit reduced order parameters upon ligand binding. In particular, strands B3, B5, and B6, which have most of the residues involved in the dimer interaction, have the reduced order parameters in the steroid-bound KSI, indicating the increased high-frequency (pico- to nanosecond) motions in the intersubunit region of this homodimeric enzyme. Our results differ from those of previous studies on the backbone dynamics of monomeric proteins, in which high-frequency internal motions are typically restricted upon ligand binding.

Binding Sites↗

Strong anisotropy of superexchange in the copper-oxygen chains of La(14)-xCaxCu24O41.

Electron spin resonance data of Cu2+ ions in La(14)-xCaxCu24O41 single crystals (x = 9,11,12) reveal a very large width of the resonance line in the paramagnetic state. This signals an unusually strong anisotropy of approximately 10% of the isotropic Heisenberg superexchange in the Cu-O chains of this compound. The strong anisotropy can be explained by the specific geometry of two symmetrical 90 degrees Cu-O-Cu bonds, which boosts the importance of orbital degrees of freedom. Our data show the apparent limitations of the applicability of an isotropic Heisenberg model to the low-dimensional cuprates.

Journal Article↗

Prolonged activation of mitogen-activated protein kinases during NSAID-induced apoptosis in HT-29 colon cancer cells.

The mechanisms of the antineoplastic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) still are unknown, but the induction of apoptosis is one of the possible mechanisms. We attempted to demonstrate the role of mitogen-activated protein (MAP) kinases, generally considered to be important mediators of proliferative and apoptotic signals, in NSAID-induced colon cancer cell apoptosis. Apoptosis was detected by demonstration of DNA fragmentation in agarose gel electrophoresis. Cell death was assessed by trypan blue dye exclusion method. MAP kinase activation was assessed by Western blot using phosphospecific antibodies to MAP kinases. Kinase assay using activating transcription factor-2 (ATF-2) fusion protein as a substrate was also performed for measuring p38 MAP kinase activity. For the inhibition of p38 MAP kinase, pyridinylimidazole compound (SB203580) was utilized. Caspase-3 activity was measured using the tetrapeptide fluorogenic substrate Ac-DEVD-AMC. Treatment of HT-29 cells with NSAIDs results in time- and dose-dependent induction of apoptosis, accompanied by sustained activation of all three MAP kinase subfamilies. The SB203580, a p38 MAP kinase inhibitor, reduced indomethacin-induced cell death by 43%, while PD098059, a MAPK/ERK kinase (MEK)1 inhibitor, did not affect cell death. p38 MAP kinase and caspase-3 activation were not significantly interlinked in indomethacin-induced apoptosis. From these results, we conclude that NSAIDs can induce prolonged activation of MAP kinases in colon cancer cells and that, of these, p38 MAP kinase may play a partial but significant role in indomethacin-induced apoptosis.

Anti-Inflammatory Agents, Non-Steroidal↗

Structure and enzymology of Delta5-3-ketosteroid isomerase.

The three-dimensional structures of Delta5-3-ketosteroid isomerases from two different bacterial species have been determined. The structures reveal an unusually apolar active site, in which each of several competitive inhibitors of the enzyme are held by two hydrogen bonds with the general acids Tyr14 and Asp99, and by hydrophobic interactions. The hydrogen bond between the Tyr14 hydroxyl and the C3 oxyanion of a transition-state analog is a low-barrier hydrogen bond, as indicated by a highly deshielded nuclear magnetic resonance. Structural and other biochemical studies have enabled the proposal of a detailed catalytic mechanism for Delta5-3-ketosteroid isomerase and provided a major thrust towards understanding the mechanism not only in chemical terms but also in energetics terms.

Binding Sites↗

Bis[3,6-bis(6-methyl-2pyridyl)pyridazine-kappa2N2,N3]chlorocopper(II) perchlorate.

The title compound, [CuCl(C16H14N4)2]ClO4, consists of a mononuclear complex cation and a perchlorate anion. The coordination of the copper(II) ion exhibits a trigonal bipyramidal geometry, where the equatorial plane is composed of the Cl atom and two N atoms of the two pyridazine rings, and the axial positions are occupied by the N atoms of two methylpyridine rings.

Crystallography, X-Ray↗