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Biomedical subjects

Y Kwon

Publications and source records attributed to Y Kwon.

At least 19 recordsLinked to original sources
PubMed1999

Survey of extended-spectrum beta-lactamases in clinical isolates of Escherichia coli and Klebsiella pneumoniae: prevalence of TEM-52 in Korea.

Two hundred ninety isolates of Escherichia coli were investigated for the production of extended-spectrum beta-lactamases (ESBLs). Fourteen (4.8%) of the 290 strains were found to produce ESBLs. Each of the 14 strains produced one or two ESBLs, as follows: 10 strains produced TEM-52, 1 strain produced SHV-2a, 1 strain produced SHV-12, 1 strain produced a CMY-1-like enzyme, and 1 strain expressed SHV-2a and a CMY-1-like enzyme. Another two strains for which the MICs of ceftazidime and cefoxitin were high, were probable AmpC enzyme hyperproducers. Because of the high prevalence of TEM-52 in E. coli isolates, we further investigated the TEM-type ESBLs produced by Klebsiella pneumoniae in order to observe the distribution of TEM-52 enzymes among Enterobacteriaceae in Korea. All TEM enzymes produced by 12 strains of K. pneumoniae were identified as TEM-52. To evaluate the genetic relatedness among the organisms, ribotyping of TEM-52-producing E. coli and K. pneumoniae was performed. The ribotyping profiles of the organisms showed similar but clearly different patterns. In conclusion, TEM-52 is the most prevalent TEM-type ESBL in Korea.

Bacterial Proteins↗
PubMed1999

Radiologic and histopathologic changes after Gamma Knife radiosurgery for acoustic schwannoma.

Gamma knife radiosurgery (GKRS) is a widely used treatment option for acoustic schwannomas, 3 cm in diameter or less. Between May 1990 and February 1998, 102 acoustic tumors in 101 patients were treated with GKRS. There are 77 patients with a follow-up period of more than six months (mean 55, range 7 to 90 months). Seventy (91%) of these tumors have remained unchanged or reduced in volume. After GKRS there was an increase in volume in seven cases. In four the volume increase affected solid tumour. Among these, three patients were in stable condition and are being observed. One of these patients developed brain stem compression symptoms and was operated. In another three cases, cysts with multiple septa developed medial to the tumor and compressed the brain stem and fourth ventricle, thus necessitating post-GKRS surgery. In these three patients, MRI had shown loss of central contrast enhancement followed by its return. Histological findings at surgery before and after GKRS were compared for these four tumours. In spite of the MRI changes, there were no definite histological findings after GKRS which could be attributed to radiation induced changes. The development of cysts occurred after the treatment of larger tumors.

Adolescent↗
PubMed1998

Induction of topoisomerase II-mediated DNA cleavage by a protoberberine alkaloid, berberrubine.

Topoisomerase II is the cytotoxic target for a number of clinically relevant antitumor drugs. Berberrubine, a protoberberine alkaloid which exhibits antitumor activity in animal models, has been identified as a specific poison of topoisomerase II in vitro. Topoisomerase II-mediated DNA cleavage assays showed that berberrubine poisons the enzyme by stabilizing topoisomerase II-DNA cleavable complexes. Subsequent proteinase K treatments revealed that berberrubine-induced DNA cleavage was generated solely by topoisomerase II. Topoisomerase II-mediated DNA religation with elevated temperature revealed a substantial reduction in DNA cleavage induced by berberrubine, to the extent comparable to that of other prototypical topoisomerase II poison, etoposide, suggesting that DNA cleavage involves stabilization of the reversible enzyme-DNA cleavable complex. However, the step at which berberrubine induces cleavable complex may differ from that of etoposide as revealed by the difference in the formation of the intermediate product, nicked DNA. This suggests that berberrubine's primary mode of linear formation may involve trapping nicked molecules, formed at transition from linear to covalently closed circular DNA. Unwinding of the duplex DNA by berberrubine is consistent with an intercalative binding mode for this compound. In addition to the ability to induce the cleavable complex mediated with topoisomerase II, berberrubine at high concentrations was shown to specifically inhibit topoisomerase II catalytic activity. Berberrubine, however, did not inhibit topoisomerase I at concentrations up to 240 microM. Cleavage sites induced by topoisomerase II in the presence of berberrubine and etoposide were mapped in DNA. Berberrubine induces DNA cleavage in a site-specific and concentration-dependent manner. Comparison of the cleavage pattern of berberrubine with that of etoposide revealed that they share many common sites of cleavage. Taken together, these results indicate that berberrubine represents a new class of antitumor agent which exhibits the topoisomerase II poison activity as well as catalytic inhibition activity and may have a potential clinical value in cancer treatment.

Berberine↗
PubMed1998

Survey of Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases: prevalence of SHV-12 and SHV-2a in Korea.

Fifty-three clinical isolates of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae collected from three hospitals in Korea were investigated for phenotypical and genotypical characterizations. Among these, 39 strains (74%) were shown by isoelectric focusing to carry SHV-type beta-lactamases: 27 strains showed the pI 8.2 beta-lactamase, and another 12 strains showed the pI 7.6 beta-lactamase. The SHV gene of each of these strains was amplified by PCR, followed by nucleotide sequencing analysis. The gene of the pI 8.2 beta-lactamase was found to be identical to the sequences encoding SHV-12, and the gene of the pI 7.6 beta-lactamase was identical to the sequences encoding SHV-2a. A total of eight cefoxitin-resistant strains were found to have the plasmid-mediated AmpC-type beta-lactamase, with a pI of 8.0, and this was confirmed to be CMY-1 beta-lactamase by PCR and hybridization analysis. Noteworthy in this study is the fact that SHV-12 and SHV-2a have been the most commonly identified SHV-type ESBLs in Korea.

Anti-Bacterial Agents↗
PubMed1998

Gamma knife treatment of acoustic neurinoma.

The results of treatment of acoustic neurinomas using Gamma Knife radiosurgery (GKR) during a 6-year period in our center were reviewed. Since May 7, 1990, we treated 88 cases of acoustic neurinoma with GKR. During a 52-month mean follow-up period, MRI was obtained in 63 patients. Reduction in tumor size occurred in 34 (54%) cases, and another 27 (42.8%) tumors showed no change. The tumor control rate was thus 95%. Tumor size increased in 3 (4.8%) cases, but one case is still in early follow-up. Two cases were operated after GKR. Histological examination of the tumors removed at surgery 8 months after GKR were obtained. The examinations showed enlargement of nucleoli and cytoplasm and proliferation of endothelial cells due to delayed radiation changes. Post-GKR facial neuropathy was noted in 7 (8.8%) patients, of which 4 recovered during the follow-up period. The tumor volume, margin dose, number of isocenters and marginal isodose did not have any statistically significant relationship with the development of facial neuropathy. Transient trigeminal neuropathy were noted in 3 patients. Hearing was preserved in 2 of 3 hearing patients. In conclusion, our GKR results for acoustic neurinomas were very similar to the previously reported series, which makes GKR for acoustic tumors an excellent treatment modality for small- to medium-sized tumors with or without microsurgical tumor removal.

Adolescent↗
PubMed1998

Plasma glucose levels are reduced in rats and mice treated with an inhibitor of glucose-6-phosphate translocase.

The activity of glucose-6-phosphatase (G-6-Pase) in isolated rat microsomes was inhibited by a new selective inhibitor of the multi-subunit G-6-Pase system, 1-[2-(4-chloro-phenyl)-cyclopropylmethoxy]-3,4-dihydroxy-5-(3-imid azo[4,5-b]pyridin-1-yl-3-phenyl-acryloyloxy)-cyclohexanecarboxylic acid (compound A) with a 50% inhibitory concentration (IC50) of approximately 10 nmol/l. Compound A (500 nmol/l) inhibited the uptake of [14C]glucose-6-phosphate (G-6-P) into intact isolated rat microsomes, confirming that this agent blocks G-6-P translocation, as suggested by previous studies using intact and permeabilized microsomes. The inhibition of microsomal G-6-P transport by compound A was associated with inhibition of the rate of glucose output from rat hepatocytes incubated in the presence of 25 nmol/l glucagon (IC50 approximately 320 nmol/l.) Compound A (1 micromol/l) also inhibited the basal rate of glucose production by rat hepatocytes by 47%. Intraperitoneal administration of compound A to fasted mice lowered circulating plasma glucose concentrations dose-dependently at doses as low as 1 mg/kg. This effect was comparatively short-lived; glucose lowering was maximal at 30 min after dosing with 100 mg/kg compound A (-71%) and declined thereafter, being reversed within 3 h. A similar time course of glycemic response was observed in fasted rats; glucose lowering was maximal 30 min after dosing with 100 mg/kg compound A (-36%) and declined until the effect was fully reversed by 3 h postdose. In rats subjected to compound A treatment, liver glycogen content was increased. G-6-P and lactate levels were maximally elevated 30 min after dosing and declined thereafter. Cumulatively, these results suggest that the mechanism of glucose lowering by compound A was via inhibition of G-6-Pase activity, mediated through inhibition of the T1 subunit of the microsomal G-6-Pase enzyme system. Drug levels measured over the same time course as that used to assess in vivo efficacy peaked within 30 min of administration, then declined, which is consistent with the transient changes in plasma glucose and liver metabolites.

Animals↗
PubMed1997

A solenoid-like coil producing transverse RF fields for MR imaging.

A solenoidal RF coil is presented that generates an RF field only perpendicular to the long axis, so that it can be used longitudinally in the usual superconducting solenoid magnet for NMR. This new design is superior to the traditional saddle coil or Helmholtz pair. Applications for the coil will include imaging of legs, arms, etc., as well as analytical application in high-resolution NMR. A tilted single-turn-solenoid, which has the plane of each loop tilted with respect to the cylinder axis, is implemented to generate an RF field with a component perpendicular to the coil-cylinder axis. The novel addition of an eddy-current coil eliminates the undesirable longitudinal component of the RF field, leaving an RF field entirely perpendicular to the coil-cylinder axis. By inserting the eddy coil, the spatial homogeneity of the transverse RF field is greatly improved, with significant increases in the H1 field strength and receiving sensitivity. Images with the eddy-coil-modified tilted solenoid are remarkably uniform in intensity over a large useful volume.

Hand↗
PubMed1997

Membrane transport in hepatic clearance of drugs. I: Extended hepatic clearance models incorporating concentration-dependent transport and elimination processes.

PURPOSE: The objective of the present study was to develop hepatic clearance models which incorporate a unidirectional carrier-mediated uptake and bidirectional diffusional transport processes for drug transport in the sinusoidal membrane of hepatocytes as well as nonlinear intrinsic elimination. METHODS: Two models were derived which view the liver as two separate compartments, i.e., sinusoid and hepatocyte. Model I assumes the instantaneous complete mixing of drugs within each compartment (similar to that of the "well-stirred" model), while model II assumes that the drug concentrations in both compartments decrease progressively in the direction of the hepatic blood flow path (similar to that of the "parallel-tube" model). Computer simulations were performed using a range of steady-state infusion rates for a substrate, while varying the Vmax (capacity) and Km (Michaelis-Menten constant) for the carrier-mediated uptake process, the diffusional clearance, the Vmax and Km for the intrinsic elimination process, blood flow and protein binding. RESULTS: Simulations in which Vmax and Km for the sinusoidal membrane transporter and the diffusional clearance were varied, demonstrated that these membrane transport processes could affect the clearance of drugs to a significant extent in both models. The estimates for clearance of substrates with the same pharmacokinetic parameters are always lower in model I than in model II, although the quantitative differences in parameter estimates between models varied, depending on the steady state infusion rates. CONCLUSIONS: These more general hepatic clearance models will be most useful for describing the hepatic clearance of hydrophilic compounds, such as organic anions or cations, which exhibit facilitated uptake and limited membrane diffusion in hepatocytes.

Biological Transport↗
PubMed1997

Membrane transport in hepatic clearance of drugs. II: Zonal distribution patterns of concentration-dependent transport and elimination processes.

PURPOSE: The objective of the present simulation study was to investigate the effects of hepatic zonal heterogeneity of membrane transporter proteins and intrinsic elimination activities on hepatic clearance (CL) and drug concentration gradient profiles in the sinusoidal blood and hepatocytes. METHODS: The model used in the simulations assumes an apparent unidirectional carrier-mediated transport and a bidirectional diffusion of substrates in the hepatic sinusoidal membrane as well as a nonlinear intrinsic elimination. Three different distribution patterns of the transporter and the metabolizing enzyme along the sinusoidal flow path were used for the simulations. The effects of changes in the Michaelis-Menten parameters for those nonlinear processes, and in the unbound fractions of the drug in blood and tissue components were investigated. RESULTS: Significant differences in CL occurred when the distribution patterns of the transporter and/or the metabolizing enzyme activities were altered under nonlinear conditions. The highest CL values were observed when the transporter and the metabolizing enzyme had similar distribution patterns within the liver acinus, while opposite distribution patterns produced the lowest CL values. Tissue concentration profiles were significantly affected by the distribution patterns of the transporter, but the changes in blood concentration profiles were relatively small. Altering protein binding in blood produced significant changes in CL, and blood and tissue concentration gradients, while altering protein binding in tissue affected only drug accumulation patterns within hepatocytes, regardless of the distribution patterns of the transporter or the metabolizing enzyme. CONCLUSIONS: The present simulations demonstrate that hepatic zonal heterogeneities in the transporter and the metabolizing enzyme activities can significantly influence hepatic clearance and/or drug concentration gradient profiles in the sinusoidal blood and hepatocytes.

Biological Transport↗
PubMed1996

Inhibitors of P-glycoprotein-mediated daunomycin transport in rat liver canalicular membrane vesicles.

P-glycoprotein (P-gp), the multidrug resistance (MDR) gene product, is exclusively located on the canalicular membrane of hepatocytes. Recent studies using isolated rat canalicular liver plasma membrane (cLPM) vesicles indicate that daunomycin (DNM) is a substrate for the ATP-dependent P-gp efflux system in the rat liver. The isoforms of P-gp present in cLPM and in cancer cell lines differ in that the major form present in the liver represents the gene product of mdr2 in mice (MDR3 in humans; class III) while the isoform of P-gp in cancer cells is the gene product of mdr1 in mice (MDR1 in humans, class I). The objective of this study was to examine the inhibitory effects of various organic compounds, most of which have been studied previously in MDR cancer cells, on P-gp-mediated [3H]DNM uptake into cLPM. Also, the stereospecificity of P-gp for its substrates was investigated by comparing the inhibitory effects of the enantiomers and the racemic mixtures of verapamil and propranolol. DNM exhibited ATP-dependent active transport into rat liver cLPM with a Km of 26.8 +/- 13.4 microM and a Vmax of 4.9 +/- 0.8 nmol/45 s/mg of protein (n = 4). ADP, AMP, and a nonhydrolyzable ATP analogue did not increase DNM transport over the control value. Thirty-one potential inhibitors were examined; only acridine orange, doxorubicin, verapamil, propranolol, phosphatidylcholine, beta-estradiol glucuronide, and DNM itself showed statistically significant inhibition of [3H]DNM uptake into cLPM. These results suggest that only a limited number of substrates bind to or are transported across the hepatic canalicular membrane via P-gp. Phosphatidylcholine, a substrate for the gene product of the class III P-gp gene, produced significant inhibition of [3H]DNM transport (30.6% at a 10-fold-higher substrate concentration), suggesting that transport may be mediated, at least in part, by this P-gp gene product. There were no statistically significant differences in the inhibitory effects of the enantiomers and racemate of verapamil on [3H]DNM transport into cLPM, but the enantiomers of propranolol exhibited stereospecific inhibition of DNM transport. (R)-(+)-Propranolol produced a statistically significant inhibition of [3H]DNM transport similar to that observed with the racemic mixture, while (S)(-)-propranolol showed no inhibition. These findings suggest that bile canalicular P-gp may exhibit stereospecificity of binding or transport for its substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Theoretical considerations on two equations for estimating the extent of absorption after oral administration of drugs.

PURPOSE: The amount of drug absorbed into portal blood after oral dosing (Dp.o,g) has been estimated using Fick's principle (Q-method), i.e., Dp.o,g = Qh x (AUCp.o,g--AUCp.o,c), where Qh is the portal blood flow rate, and AUCp.o,g and AUCp.o,c are the areas under the concentration-time curves of portal vein and systemic blood after oral dosing, respectively. However, this method may underestimate Dp.o,g, when the drug is subject to systemic intestinal elimination. An alternate equation (CL-method; Dp.o,g = CLs x AUCp.o,g) is described using a simple pharmacokinetic model, to estimate Dp.o,g in the presence of systemic intestinal elimination, where CLs is systemic clearance. METHODS: The model is composed of central, intestine and liver compartments, assuming that drug is eliminated by intestinal and/or hepatic pathways only. A comparison of both methods for estimating Dp.o,g was made using computer-simulation or experimental data of phenacetin from the literature. RESULTS: The simulation study demonstrated that the Q-method underestimated Dp.o,g in the presence of significant intrinsic intestinal clearance, compared to the CL-method. The similar results were observed using the experimental data of phenacetin. CONCLUSIONS: The CL-method can provide a better estimate of Dp.o,g, while the Q-method may underestimate Dp.o,g, when there is significant systemic intestinal elimination of drugs after oral administration. In addition, useful information for understanding the relationship between the extent of absorption and the first-pass effect by intestine and/or liver after oral dosing of drugs can be obtained from the present approach.

Administration, Oral↗
PubMed1996

Acute subdural hematoma caused by a ruptured giant intracavernous aneurysm: case report.

A case of a giant intracavernous carotid artery aneurysm that presented as an acute subdural hematoma is reported. The patient was initially treated unsuccessfully with endovascular aneurysmal embolization and subsequently underwent attempted microsurgical clipping with preservation of the parent artery. At operation, an angiogram showed occlusion of the parent vessel, and the aneurysm was trapped by occlusion of the internal carotid artery. The patient did well for 2 days postoperatively but then developed contralateral progressive hemiplegia and aphasia. Emergent subsequent exploration and middle cerebral artery embolectomy were performed, and the hemiplegia and aphasia resolved rapidly. At 2-year follow-up, the patient continues to do well. To our knowledge, this is the first reported case of a patient who survived an acute subdural hematoma caused by an intracavernous carotid artery aneurysm.

Acute Disease↗