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Biomedical subjects

S W Cho

Publications and source records attributed to S W Cho.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of ADP on different inhibitory properties of brain glutamate dehydrogenase isoproteins by perphenazine.

Incubation of glutamate dehydrogenase isoproteins (GDH I and GDH II) from bovine brains with perphenazine resulted in a time-dependent loss of enzyme activity. 2-Oxoglutarate and NADH, separately or together, gave partial but not complete protection against the inhibition. Although there were no detectable differences between GDH I and GDH II in inhibition by perphenazine in the absence of ADP, the sensitivities to the inhibition by the drug were significantly distinct for the two isoproteins in the presence of ADP. Low concentrations of ADP (0.05-0.20 mM) did not interfere with the inhibition of GDH I and GDH II by perphenazine. However, in the presence of high concentrations of ADP (0.5-1.0 mM), inhibitory effects of perphenazine on GDH isoproteins were significantly diminished as determined by enzyme kinetics and quantitative affinity chromatography on perphenazine-Sepharose. GDH I was more sensitively reacted with ADP than GDH II on the inhibition by perphenazine. Since physiological ADP levels can vary from 0.05 to > 1.0 mM depending on the rate of oxidative phosphorylation, our results suggest a possibility that two types of GDHs are differently regulated by the antipsychotic actions of perphenazine depending on the physiological concentrations of ADP. GTP and L-leucine, other well-known allosteric regulators, did not affect the inhibitory actions of perphenazine on bovine brain GDH isoproteins.

Adenosine Diphosphate↗
PubMed2001

Cassette mutagenesis of lysine 130 of human glutamate dehydrogenase. An essential residue in catalysis.

It has been suggested that reactive lysine residue(s) may play an important role in the catalytic activities of glutamate dehydrogenase (GDH). There are, however, conflicting views as to whether the lysine residues are involved in Schiff's base formation with catalytic intermediates, stabilization of negatively charged groups or the carbonyl group of 2-oxoglutarate during catalysis, or some other function. We have expanded on these speculations by constructing a series of cassette mutations at Lys130, a residue that has been speculated to be responsible for the activity of GDH and the inactivation of GDH by pyridoxal 5'-phosphate (PLP). For these studies, a 1557-bp gene that encodes human GDH has been synthesized and inserted into Escherichia coli expression vectors. The mutant enzymes containing Glu, Gly, Met, Ser, or Tyr at position 130, as well as the wild-type human GDH encoded by the synthetic gene, were efficiently expressed as a soluble protein and are indistinguishable from that isolated from human and bovine tissues. Despite an approximately 400-fold decrease in the respective apparent Vmax of the Lys130 mutant enzymes, apparent Km values for NADH and 2-oxoglutarate were almost unchanged, suggesting the direct involvement of Lys130 in catalysis rather than in the binding of coenzyme or substrate. Unlike the wild-type GDH, the mutant enzymes were unable to interact with PLP, indicating that Lys130 plays an important role in PLP binding. The results with analogs of PLP suggest that the aldehyde moiety of PLP, but not the phosphate moiety, is required for efficient binding to GDH.

Amino Acid Sequence↗
PubMed2001

Brain succinic semialdehyde dehydrogenase: identification of reactive lysyl residues labeled with pyridoxal-5'-phosphate.

An NAD+ dependent succinic semialdehyde dehydrogenase from bovine brain was inactivated by pyridoxal-5'- phosphate. Spectral evidence is presented to indicate that the inactivation proceeds through formation of a Schiff's base with amino groups of the enzyme. After NaBH(4) reduction of the pyridoxal-5'-phosphate inactivated enzyme, it was observed that 3.8 mol phosphopyridoxyl residues were incorporated/enzyme tetramer. The coenzyme, NAD+, protected the enzyme against inactivation by pyridoxal-5'-phosphate. The absorption spectrum of the reduced and dialyzed pyridoxal-5'-phosphate-inactivated enzyme showed a characteristic peak at 325 nm, which was absent in the spectrum of the native enzyme. The fluorescence spectrum of the pyridoxyl enzyme differs completely from that of the native enzyme. After tryptic digestion of the enzyme modified with pyridoxal-5'-phosphate followed by [3H]NaBH4 reduction, a radioactive peptide absorbing at 210 nm was isolated by reverse-phase HPLC. The sequences of the peptide containing the phosphopyridoxyllysine were clearly identical to sequences of other mammalian succinic semialdehyde dehydrogenase brain species including human. It is suggested that the catalytic function of succinic semialdehyde dehydrogenase is modulated by binding of pyridoxal-5'-phosphate to specific Lys(347) residue at or near the coenzyme-binding site of the protein.

Aldehyde Oxidoreductases↗
PubMed2001

Efficacy of flubendazole and albendazole against Trichinella spiralis in mice.

Efficacy of flubendazole and albendazole against Trichinella spiralis in mice were studied. ICR mice were experimentally infected with Trichinella spiralis and treated with either flubendazole (FBZ) or albendazole (ABZ) at four different stages of the parasite life-cycle. Oral administration of either FBZ or ABZ at 20 mg/kg and 50 mg/kg on 2 h, 8 h and 24 h (pre-adult stage) after infection eliminated 94.7-100% of adults as determined at necropsy on day 7 post infection (p.i.) and 96.9-100% of larvae on day 45 p.i. FBZ was more effective than ABZ against adult T. spiralis (at 2 to 6 days p.i.), when treated with a dosage of 20 mg/kg for 5 consecutive days (99.4% and 46.0% reduction with respect to the control group). Against migrating larval T. spiralis, FBZ was more effective than ABZ at 20 mg/kg for five consecutive days (on days 11-15 p.i.), and the reduction rate of recovered larvae were 99.6% (FBZ) and 80.8% (ABZ) respectively. FBZ was more effective against early encapsulated larval T. spiralis (at 21 to 25 days p.i.), than ABZ when both were given at 20 mg/kg for five consecutive days (99.8% and 45.4% reduction, respectively). In conclusion, flubendazole was more effective than albendazole against adult and parenteral stages of Trichinella spiralis in mice.

Albendazole↗
PubMed2001

Self-expanding coil stent with a long delivery system for palliation of unresectable malignant gastric outlet obstruction: a prospective study.

BACKGROUND AND STUDY AIMS: Peroral intubation of a self-expanding metal stent is usually difficult in patients with unresectable malignant gastric outlet obstruction, because the delivery systems currently available are not long enough and cannot easily pass the angulated gastroduodenal structure. We carried out a prospective study to assess the efficacy of a coil stent with a newly developed long delivery system, for palliation of unresectable malignant gastric outlet obstruction. PATIENTS AND METHODS: In 29 patients with unresectable malignant gastric outlet obstruction, caused by gastric cancer (26 patients), pancreatic head cancer (two patients), or duodenal cancer (one patient), peroral intubation of a self-expanding nickel-titanium coil stent was attempted, using a lengthened delivery system of 150 cm, under endoscopic and fluoroscopic guidance. RESULTS: Management was successful in 26 of 29 patients (89.7 %) without immediate major complications. In one patient in whom peroral intubation failed, percutaneous intubation of the coil stent via percutaneous endoscopic gastrostomy was done. After insertion of the coil stent, food ingestion with symptomatic improvement with regard to vomiting was achieved in 26 of 27 patients (96.3 %), including the patient with percutaneous stent insertion. During the follow-up period, dysphagia and Karnofsky scores improved significantly. Stent migration occurred in two patients, and tumor ingrowth in another two; re-intervention was done successfully performed in two instances. The mean survival time was 124 days (range 34 - 310 days) in the 22 patients who had no need for re-intervention during follow-up; among these was a patient who experienced stent occlusion by food material, which was easily corrected with endoscopic flushing. CONCLUSIONS: Peroral intubation of a self-expanding coil stent using a long delivery system is a safe and effective palliative technique for unresectable malignant gastric outlet obstruction, and significantly improves the quality of life of patients.

Adult↗
PubMed2001

Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats.

BACKGROUND: Although antisecretory medications such as histamine type II receptor antagonists or proton pump inhibitors have been used to treat reflux oesophagitis, a considerable number of patients do not achieve complete mucosal healing or suffer from either sustained symptoms or ensuing complications, suggesting other damaging factors or impaired mucosal resistance are also involved in the pathogenesis of reflux oesophagitis. AIMS: The present study was designed to evaluate oxidative stress as the major pathogenic factor of reflux oesophagitis and to determine the usefulness of antioxidants in the treatment of reflux oesophagitis. MATERIALS AND METHODS: Reflux oesophagitis was induced by insertion of a 3 mm calibre ring into the duodenum, 1 cm distal to the ligament of Treitz, in Sprague-Dawley rats. RESULTS: DA-9601, a novel antioxidant substance, significantly attenuated the gross and histopathological scores of reflux oesophagitis compared with those treated with ranitidine alone or reflux oesophagitis controls in a dose dependent manner. Only scattered erosions were observed in the antioxidant pretreated group but acid suppression by ranitidine was not effective in decreasing the severity of reflux oesophagitis. Significantly increased amounts of malondialdehyde (MDA), increased nuclear factor kappaB (NFkappaB) activation, and depletion of reduced glutathione (GSH) were observed in experimentally induced reflux oesophagitis. DA-9601 pretreatment attenuated the decrement in mucosal GSH levels and decreased MDA formation significantly. DA-9601 treatment caused significant reductions in activation of NFkappaB transcription factor, especially the p50 subunit, in accordance with the significantly higher levels of inhibitory protein of NFkappaB expression. CONCLUSION: Reflux oesophagitis caused considerable levels of oxidative stress in the oesophageal mucosa and antioxidant treatment should be considered as supplementary therapy in the prevention or treatment of reflux oesophagitis with acid suppression.

Animals↗
PubMed2001

Emergence of vaccine-induced escape mutant of hepatitis B virus with multiple surface gene mutations in a Korean child.

The S protein of hepatitis B virus is the principal component of virus envelope and the primary target of anti-HBs response. Mutants or variants that escape neutralization by anti-HBs have been selected during immunoprophylaxis of HBV after birth and liver transplantation. We investigated a case of a Korean child who was vaccinated at birth against hepatitis B and also given hepatitis B immunoglobulin, but nevertheless later became infected with the virus. Hepatitis B virus-specific deoxyribonucleic acid covering the region of genome encoding the predominant "a" determinant of hepatitis surface antigen was amplified using polymerase chain reaction, and the nucleotide sequence was determined. We present for the first time in Korea the independent emergence of an escape mutant with substitution of arginine for glycine at amino acid 145 and proline for glutamate at amino acid 120 in "a" determinant after immunization.

Cloning, Molecular↗
PubMed2000

Elevation of the gamma-aminobutyric acid transaminase expression in the gerbil CA1 area after ischemia-reperfusion damage.

gamma-Aminobutyric acid-transaminase (GABA-T) plays an important role in the metabolism of GABA, particularly in the neurons or glial cells. The present study was undertaken to determine the alteration of GABA-T expression in the gerbil hippocampus after ischemia-reperfusion. In the sham, GABA-T(+) neurons were scattered in the hippocampus proper and dentate gyrus. The intensity of the GABA-T immunoreactivity had nearly disappeared in the interneurons at 12 h after ischemia. In contrast, 24 h post-ischemia the dramatic augmentation of GABA-T immunoreactivity in the pyramidal cells was observed in the CA1 area but not in the CA2 or CA3 areas. Forty-eight hours after ischemia-reperfusion, its immunoreactivity was preserved in the CA1 neurons. These results suggest that the over-expression of GABA-T in the CA1 area may be related to delayed neuronal death after ischemia-reperfusion insult.

4-Aminobutyrate Transaminase↗
PubMed2000

Regulatory properties of glutamate dehydrogenase from Sulfolobus solfataricus.

The purified glutamate dehydrogenase (GDH) from Sulfolobus solfataricus showed remarkable thermostability and retained 90-95% of the initial activity after incubation at -20 degrees C, 4 degrees C, and 25 degrees C for up to 6 months. Unlike mammalian GDHs, the activity of GDH from Sulfolobus solfataricus was not significantly affected by the presence of various allosteric effectors such as ADP, GTP, and leucine. Incubation of GDH with increasing concentration of o-phthalaldehyde resulted in a progressive decrease in enzyme activity, suggesting that the o-phthalaldehyde-modified lysine or cysteine is directly involved in catalysis. The inhibition was competitive with respect to both 2-oxoglutarate (Ki = 30 microM) and NADH (Ki = 100 microM), further supporting a possibility that the o-phthalaldehyde-modified residues may be directly involved at the catalytic site. The modification of GDH by the arginine-specific dicarbonyl reagent phenylglyoxal was also examined with the view that arginine residues might play a general role in the binding of coenzyme throughout the family of pyridine nucleotide-dependent dehydrogenases. The purified GDH was inactivated in a dose-dependent manner by phenylglyoxal. Either NADH or 2-oxoglutarate did not gave any protection against the inactivation caused by a phenylglyoxal. This result indicates that GDH saturated with NADH or 2-oxoglutarate is still open to attack by phenylglyoxal. Phenylglyoxal was an uncompetitive inhibitor (Ki = 5 microM) with respect to 2-oxoglutarate and a noncompetitive inhibitor (Ki = 6 microM) with respect to NADH. The above results suggests that the phenylglyoxal-modified arginine residues are not located at the catalytic site and the inactivation of GDH by phenylglyoxal might be due to a steric hindrance or a conformational change affected by the interaction of the enzyme with its inhibitor.

Dose-Response Relationship, Drug↗
PubMed2000

Anticonvulsant compounds from the wood of Caesalpinia sappan L.

80% Aqueous MeOH extracts from the wood of Caesalpinia sappan, which showed remarkable anticonvulsant activity, were fractionated using EtOAc, n-BuOH, and H2O. Among them, the EtOAc fraction significantly inhibited the activities of two GABA degradative enzymes, succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR). Repeated column chromatographies for the fraction guided by activity test led to the isolation of the two active principal components. Their chemical structures were determined to be sappanchalcone and brazilin based on spectral data. The pure compounds, sappanchalcone (1) and brazilin (2), inactivated the SSAR activities in a dose dependent manner, whereas SSADH was inhibited partially by sappanchalcone and not by brazilin.

Aldehyde Oxidoreductases↗
PubMed2000

Effects of solvent selection and fabrication method on the characteristics of biodegradable poly(lactide-co-glycolide) microspheres containing ovalbumin.

To demonstrate the effect of formulation conditions on the controlled release of protein from poly(lactide-co-glycolide) (PLGA) microspheres for use as a parenteral drug carrier, ovalbumin (OVA) microspheres were prepared using the W/O/W multiple emulsion solvent evaporation and extraction method. Methylene chloride or ethyl acetate was applied as an organic phase and poly(vinyl alcohol) as a secondary emulsion stabilizer. Low loading efficiencies of less than 20% were observed and the in vitro release of OVA showed a burst effect in all batches of different microspheres, followed by a gradual release over the next 6 weeks. Formulation processes affected the size and morphology, drug content, and the controlled release of OVA from PLGA microspheres.

Lactic Acid↗
PubMed2000

Mitochondrial ATPase 6 gene expression in unfertilized oocytes and cleavage-stage embryos.

OBJECTIVE: To compare the level of mitochondrial ATPase 6 gene expression in unfertilized oocytes and cleavage-stage embryos. DESIGN: Reverse transcription polymerase chain reaction was performed in unfertilized oocytes and cleavage-stage embryos derived from tripronucleate embryos to determine ATPase 6 gene expression. SETTING: Department of Obstetrics and Gynecology, Human Genetics Laboratory, Infertility Medical Center of CHA General Hospital, College of Medicine, Pochon CHA University, Seoul, Korea. PATIENT(S): Oocytes were obtained from infertile couples undergoing in vitro fertilization. INTERVENTION(S): Unfertilized oocytes collected at 48 hours after retrieval and cleavage-stage embryos derived from tripronucleate embryos were prepared for evaluation of mitochondrial gene expression. MAIN OUTCOME MEASURE(S): Comparison of ATPase 6 gene expression by using single-cell reverse transcription polymerase chain reaction. RESULT(S): Expression of unfertilized oocytes decreased compared with early cleavage-stage embryos. CONCLUSION(S): Our findings of decreased ATPase 6 expression in unfertilized oocytes suggest that there may be a decrease in the mitochondrial functional capacity of oxidative phosphorylation.

Adenosine Triphosphatases↗
PubMed2000

Functional characteristics of two BKCa channel variants differentially expressed in rat brain tissues.

cDNAs encoding large-conductance Ca2+-activated K+ channel alpha-subunit (rSlo) were obtained from rat brain. From the DNA sequence of multiple rslo clones, we identified a specific sequence variation of 81 nucleotides, which is either absent from or present at the N-terminal region of a putative Ca2+-sensing domain of the channel. Transcripts containing such variations were detected in different ratios from several brain regions, and their functional significance was further examined. When heterologously expressed in Xenopus oocytes, both rSlo variants, named rSlo0 and rSlo27, generated Ca2+-activated and voltage-activated K+ currents characteristic of neuronal large-conductance Ca2+-activated K+ (BKCa) channels. Single-channel recordings of the two channels showed almost identical permeation characteristics and steady-state gating behavior. Noticeable differences between rSlo0 and rSlo27 were revealed when the macroscopic currents were measured at various voltages and intracellular Ca2+ concentrations. rSlo27 activated was more rapidly than rSlo0 in the presence of the same voltage stimulus, and the differences in these activation kinetics were dependent on the concentration of intracellular Ca2+. Despite their similar apparent affinities for Ca2+, rSlo0 and rSlo27 showed significant differences in their co-operative gating behavior. The Hill coefficient for intracellular Ca2+ was estimated to be about 3.7 for rSlo27 regardless of the membrane voltage, and that for rSlo0 was reduced from about 5 to 2 as the membrane voltage changed from 40 to 140 mV. As activation of BKCa channels is involved in rapid hyperpolarization of action potentials, the differential processing of rslo transcripts, and the generation of channels with different activation kinetics and Ca2+ cooperativity may be a mechanism for tuning the excitability of neurons in different brain regions.

Amino Acid Sequence↗
PubMed2000

Human brain GABA transaminase tissue distribution and molecular expression.

Human brain gamma-aminobutyrate transaminase is differentially expressed in a tissue-specific manner. mRNA master dot-blot analysis for 50 different human tissues, including different brain regions and fetal tissues, provided a complete map of the tissue distribution. Genomic Southern analysis revealed that the gamma-aminobutyrate transaminase gene is a single copy, at least 15 kb in size. In addition, human brain gamma-aminobutyrate transaminase cDNA was expressed in Escherichia coli using a pGEX expression vector system. Catalytically active gamma-aminobutyrate transaminase was expressed in large quantities and the purified recombinant enzyme had kinetic parameters that were indistinguishable from those isolated from other mammalian brains. The human enzyme was inactivated by a well-known antiepileptic drug vigabatrin. Values of Ki and kinact were 1 mM and 0.35 min-1, respectively. Results from inactivation kinetics suggested that human gamma-aminobutyrate transaminase is more sensitive to the vigabatrin drug than the enzyme isolated from bovine brain.

4-Aminobutyrate Transaminase↗
PubMed2000

Reversion from precore/core promoter mutants to wild-type hepatitis B virus during the course of lamivudine therapy.

The effect of lamivudine administration on the evolution of precore/core promoter mutation is unknown. The aim of this study was to determine the changes of precore/core promoter sequences in chronic type B hepatitis patients treated with lamivudine. Serial sera were obtained from 11 patients before, at the beginning of, and during therapy. Serum samples were polymerase chain reaction-amplified, and nucleotide sequences of hepatitis B virus (HBV) were analyzed. At baseline, precore and core promoter mutations were found in 6 and 4 of 11 patients, respectively. A precore stop codon mutant was replaced by a wild-type virus in all 6 patients infected with precore mutant at a median treatment of 12 months (vs. before therapy; P =.011). Mutations in the core promoter appeared in only 1 of 10 patients (vs. before therapy; P =.021). However, precore and core promoter mutations appeared in 5 and 7 of 10 patients at a median treatment of 21 months, respectively. Acute exacerbation occurred after lamivudine withdrawal in 2 patients who had hepatitis B e antigen (HBeAg) loss or seroconversion. The serum remained HBeAg-negative throughout the study period, and each of 2 patients had precore wild-type virus during acute exacerbation. HBV mutants with core gene deletions are not eliminated completely during prolonged therapy in 2 patients in whom the HBV genomes had core gene deletions at baseline. In conclusion, lamivudine therapy resulted in reversion from precore/core promoter mutants to wild-type. However, mutations in the precore and core promoter region reappeared during prolonged therapy. HBeAg-negative wild-type precore hepatitis B virus could be selected after lamivudine withdrawal in patients who had HBeAg loss or seroconversion.

Adult↗
PubMed2000

Randomized trial of N-butyl-2-cyanoacrylate compared with injection of hypertonic saline-epinephrine in the endoscopic treatment of bleeding peptic ulcers.

BACKGROUND AND STUDY AIMS: Theoretically, the injection of cyanoacrylate may be effective for peptic ulcer bleeding, but randomized clinical trials are rare. The aim of this study was to compare the efficacy of N-butyl-2-cyanoacrylate (Histoacryl) and hypertonic saline-epinephrine (HSE) in the endoscopic treatment of major peptic ulcer hemorrhage. PATIENTS AND METHODS: A total of 126 patients with major peptic ulcer hemorrhage and active bleeding or a nonbleeding visible vessel were randomly allocated to endoscopic injection with HSE (63 patients; group 1) or to injection with Histoacryl (63 patients; group 2). The two groups were well matched for age, sex, initial hemoglobin values, ulcer size and location, and bleeding stigmata. RESULTS: Initial hemostasis was achieved in 58 cases (92.1%) in group 1 and in 60 cases (95.2%) in group 2 (P=0.717). Rebleeding rates were 16 of 58 in group 1 and seven of 60 in group 2 (P=0.051). There were no significant differences regarding the rates of permanent hemostasis (51 of 63 in group 1 vs. 57 of 63 in group 2, P=0.203), emergency surgery (seven of 58 in group 1 vs. three of 60 in group 2, P=0.200), or hospital mortality due to bleeding (0 in group 1 and 0 in group 2). With regard to the rebleeding rate, there was a significant difference between group 1 and group 2 in the subgroup with active arterial bleeding (11 of 26 in group 1 and four of 29 in group 2, P=0.039) but not in the subgroup with a nonbleeding visible vessel (five of 32 in group 1 and three of 31 in group 2, P=0.708). There were no statistically significant differences in hemostatic results between the two treatment groups in the subgroups with gastric ulcers or duodenal ulcers. Although no complications followed HSE therapy, arterial embolization with infarction occurred in two patients in the Histoacryl group, of whom one died. CONCLUSIONS: Compared with HSE injection, Histoacryl injection showed no statistically significant differences in hemostatic results, except for decreasing the rebleeding rate in the patients with active arterial bleeding. However, the use of Histoacryl to control peptic ulcer bleeding should be reserved as a last resort before surgery, because of possible embolic complication.

Adult↗
PubMed2000

Life-threatening intraabdominal arterial embolization after histoacryl injection for bleeding gastric ulcer.

N-butyl-cyanoacrylate (Histoacryl) injection has become the treatment of choice for acutely bleeding esophagogastric varices, and is the only effective option for endoscopic treatment of gastric varices. Recent reports confirm the ability of Histoacryl injection therapy to achieve immediate hemostasis in cases of gastric ulcer bleeding or Dieulafoy ulcer, where conventional endoscopic hemostatic treatment had failed. Although the overall safety record of Histoacryl injection has been relatively good, there have been scattered cases of serious complications. Here, we present two patients showing life-threatening intraabdominal arterial embolization after Histoacryl injection. They had chronic gastric ulcers with active arterial bleeding. In spite of attempts at hemostatic treatment, complete hemostasis was not achieved. We injected Histoacryl, diluted with Lipiodol, into bleeding gastric ulcers, resulting in successful hemostasis. Soon after the procedure, intraabdominal arterial embolization developed in both patients. One patient survived and the other died. Based on these experiences, we would like to warn gastrointestinal endoscopists to be alert to these fatal complications, and we propose that less diluted Histoacryl seems to be preferable in cases of bleeding peptic ulcers.

Celiac Artery↗