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Biomedical subjects

W Kang

Publications and source records attributed to W Kang.

At least 19 recordsLinked to original sources

Interaction effects and pseudogap in two-dimensional lateral tunnel junctions.

Tunneling characteristics of a two-dimensional lateral tunnel junction are reported. A pseudogap on the order of Coulomb energy is detected in the tunneling density of states (TDOS) when two identical two-dimensional electron systems are laterally separated by a thin energy barrier. The Coulombic pseudogap remains robust well into the quantum Hall regime until it is overshadowed by the cyclotron gap in the TDOS. The pseudogap is modified by the in-plane magnetic field, demonstrating a nontrivial effect of the in-plane magnetic field on the electron-electron interaction.

Journal Article↗

Pharmacokinetic and pharmacodynamic modelling of the effects of glimepiride on insulin secretion and glucose lowering in healthy humans.

Glimepiride is an oral sulfonylurea antihyperglycaemic agent. We used pharmacokinetic-pharmacodynamic (PK-PD) modelling to analyse the relationship between plasma glimepiride concentration, insulin secretion and glucose lowering to determine the effects of the drug in healthy volunteers. A single 2-mg oral dose of glimepiride was administered to six healthy volunteers. The control group received a placebo. All subjects consumed 12 g of sugar immediately after drug administration in order to standardize the initial plasma glucose levels. Serial blood sampling was performed for 9 h after oral dosing. Plasma glimepiride, insulin and glucose levels were determined by validated methods (LC/MS/MS assay, hexokinase method and radioimmunoassay respectively). Time courses of plasma glimepiride concentration, insulin secretion, and glucose lowering effects were analysed by means of PK-PD modelling with the ADAPT II program. The time course of the plasma concentrations followed a two-compartmental model with a lag time. The glimepiride concentration peaked at 191.5 ng/mL at approximately 4 h after administration. The maximal increase in insulin secretion was 9.98 mIU/L and the maximal decrease in plasma glucose was 19.33 mg/dL. Both peak effects occurred at approximately 2.5 h after drug intake. The glucose disappearance model was used to analyse glimepiride's insulin secretion and glucose lowering effects. The PK-PD model described well the relationship between plasma glimepiride and its insulin secretion and hypoglycaemic effects in healthy volunteers.

Administration, Oral↗

Resonant nernst effect in the metallic and field-induced spin density wave States of (TMTSF)2ClO4.

We examine an unusual phenomenon where, in tilted magnetic fields near magic angles parallel to crystallographic planes, a "giant" resonant Nernst signal has been observed by Wu et al. [Phys. Rev. Lett. 91, 056601 (2003)] in the metallic state of an organic conducting Bechgaard salt. We show that this effect appears to be a general feature of these materials and is also present in the field-induced spin density wave phase with even larger amplitude. Our results place conditions on any model that treats the metallic state as a state with finite Cooper pairing.

Journal Article↗

77Se NMR probe of magnetic excitations of the magic angle effect in (TMTSF)2PF6.

We report 77Se spin-lattice relaxation rates for (TMTSF)2PF6, carried out in the regime where a set of spectacular transport anomalies known as the "magic angle effects" are observed. In situ resistance measurements (R(zz)) were used to verify the experimental conditions and give precise sample alignment information. We found that the 77Se T-11 exhibits no significant changes as the magnetic-field orientation is rotated through the magic angles, and conclude that there is no evidence for either a single-particle gap or a spin gap. The clearly observed field-induced spin-density wave transition temperature is also, unexpectedly, not enhanced at the magic angles.

Journal Article↗

Stereoselective inhibition of cytochrome P450 forms by lansoprazole and omeprazole in vitro.

The stereoselectivity of the inhibitory interaction potential of lansoprazole and omeprazole isomers on six human cytochrome P450 forms was evaluated using human liver microsomes. Lansoprazole enantiomers showed stereoselective inhibition of CYP2C9-catalysed tolbutamide 4-methylhydroxylation, CYP2C19-catalysed S-mephenytoin 4'-hydroxylation, CYP2D6-catalysed dextromethorphan O-demethylation, CYP2E1-catalysed chlorzoxazone 6-hydroxylation and CYP3A4-catalysed midazolam 1-hydroxylation, whereas omeprazole only inhibited CYP2C19 stereoselectively. Of the P450 forms tested, CYP2C19-catalysed S-mephenytoin 4'-hydroxylation was extensively inhibited by both the lansoprazole and omeprazole enantiomers in a competitive and stereoselective manner; the S-enantiomers of both drugs inhibited the hydroxylation more than the R-enantiomers. The estimated K(i) values determined for CYP2C19-catalysed S-mephenytoin 4'-hydroxylation were 0.6, 6.1, 3.4 and 5.7 microM for S-lansoprazole, R-lansoprazole, S-omeprazole and R-omeprazole, respectively. The results indicate that although both lansoprazole and omeprazole are strong inhibitors of CYP2C19, the inhibition of CYP2C19 by lansoprazole is highly stereoselective, whereas the inhibition by omeprazole is less stereoselective. In addition, S-lansoprazole, the most potent CYP2C19 inhibitor, is not a good CYP2C19-selective inhibitor owing to its inhibition of other P450 forms.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Pharmacokinetics and pharmacodynamics of benidipine using a slow receptor-binding model.

PURPOSE: This study examined the relationship between the plasma concentration of benidipine, a long-lasting antihypertensive agent with Ca(2+)-channel-blocking properties, and its cardiovascular effects (reduction in blood pressure and increase in heart rate) in order to assess the usefulness of pharmacokinetic-pharmacodynamic (PK-PD) modelling in describing this relationship. METHODS: Two groups of 24 healthy volunteers received either a 4- or 8-mg benidipine hydrochloride tablet; 11 additional subjects received a placebo. Serial blood sampling and PD measurements were performed over 8 h thereafter. Plasma concentrations of benidipine were measured with a validated LC/MS/MS system, and the effects on blood pressure and heart rate were assessed during the same period. A two-compartment open model with lag time was used to explain the PK properties, and the PD model was characterized by slow receptor binding, reflecting the binding of benidipine to the ion-channel receptor. RESULTS: Benidipine reached mean peak plasma concentrations of 1.04 and 3.85 ng/mL at 0.5 and 0.75 h after 4 and 8 mg doses, respectively. Peak cardiovascular effects were detected approximately 2 h after the administration of either dose. Maximal decreases in diastolic blood pressure with 4 and 8 mg of benidipine were 7.79 and 14.75 mmHg, respectively, and maximal increases in heart rate were 7.32 and 17.56 bpm, respectively. No significant changes in systolic blood pressure were observed. The cardiovascular effects were analysed according to a slow receptor-binding model. CONCLUSIONS: The tested PK-PD model successfully described the relationship between the plasma concentration of benidipine and its cardiovascular effects.

Adult↗

Cascade of quantum phase transitions in tunnel-coupled edge states.

We report on the cascade of quantum phase transitions exhibited by tunnel-coupled edge states across a quantum Hall line junction. We identify a series of quantum critical points between successive strong and weak tunneling regimes in the zero-bias conductance. Scaling analysis shows that the conductance near the critical magnetic fields B(c) is a function of a single scaling argument /B-B(c)/T(-kappa), where the exponent kappa=0.42. This puzzling resemblance to a quantum Hall-insulator transition points to the importance of interedge correlation between the coupled edge states.

Journal Article↗

Implant contraception in Singaporean women: one decade of experience in KK Women's and Children's Hospital.

INTRODUCTION: The aim of this study was to assess user acceptability and effectiveness of implant contraception in Singaporean women. METHODS: A prospective study was carried out on 553 patients who received Norplant implant in our hospital from 1 January 1992 to 31 December 2000, and followed-up till 15 July 2003. The patients' profile, side-effects, satisfaction and continuation rate of Norplant implant were studied. RESULTS: The mean age of the subjects was 29.4 (plus or minus 5.1) years. The mean parity was 2.1 (plus or minus 1) live births. More than one-half (55.2 percent) of the subjects had used other methods of contraception before. The main reason for them to switch to implant contraception was convenience (63.6 percent). Of the 516 users on follow-up, the common side-effects were menstrual irregularity (51 percent), secondary amenorrhoea (9.6 percent) and weight gain (15.7 percent). 29.3 percent of users did not experience any side-effect. There was only one contraceptive failure, which may be related to drug interaction. The Pearl Index was 0.054 per hundred women years. There was only one serious adverse event of a patient (0.2 percent) who developed severe hypertension requiring treatment. The continuation rate was 92.4 percent after one year, 80.8 percent after two years, 68.9 percent after three years and 58.5 percent after four years. The main reasons for early implant removal were side-effects and desire for future pregnancy. Re-insertion was carried out in 53.7 percent of users who had completed five years of Norplant contraception. CONCLUSION: This largest sub-dermal hormonal implant contraception study in multi-racial Singapore showed that Norplant contraception had a high degree of effectiveness with relatively high user satisfaction and continuation rate.

Adult↗

The scavenger receptor, cysteine-rich domain-containing molecule gp-340 is differentially regulated in epithelial cell lines by phorbol ester.

Gp-340 is a glycoprotein belonging to the scavenger receptor cysteine rich (SRCR) group B family. It binds to host immune components such as lung surfactant protein D (SP-D). Recent studies found that gp-340 interacts directly with pathogenic microorganisms and induces their aggregation, suggesting its involvement in innate immunity. In order to investigate further its potential immune functions in the appropriate cell lines, the expression of gp-340 in four conventional immune cell lines (U937, HL60, Jurkat, Raji), and two innate immune-related epithelial cell lines (A549 derived from lung and AGS from stomach), was examined by RT-PCR and immunohistochemistry. The resting immune cell lines showed weak or no gp-340 mRNA expression; while the two epithelial cell lines expressed gp-340 at much higher level, which was differentially regulated by phorbol myristate acetate (PMA) treatment. In the A549 cells, gp-340 was up-regulated along with the PMA-induced proinflammatory expression of both IL-6 and IL-8. In AGS cells, PMA down-regulation of gp-340 was seen in parallel with an up-regulation of the two mature gastric epithelial specific proteins TFF1 (trefoil factor 1) and TFF2, which are implicated as markers of terminal differentiation. Analysis of the distribution of gp-340, together with the TFFs and SP-D in normal lung and gastric mucosa, supported further our in vitro data. We conclude that the differential regulation of gp-340 in the two epithelial cell lines by PMA indicates that gp-340 s involvement in mucosal defence and growth of epithelial cells may vary at different body locations and during different stages of epithelial differentiation.

B-Lymphocytes↗

Accuracy of CT in local staging of gallbladder carcinoma.

PURPOSE: To evaluate the accuracy of CT for staging gallbladder cancers, especially the T-factor of the TNM staging system. MATERIAL AND METHODS: CT investigations of 100 patients with surgically proven gallbladder cancers were retrospectively analyzed. Dynamic helical CT was performed in 16 patients and conventional CT in the remaining 84. On CT, three radiologists attempted tumor staging for these patients; the majority opinion was used for final decision. According to CT protocols (dynamic helical CT vs. conventional CT) and each tumor type (thickened wall/intraluminal mass/massive), the accuracy of CT staging was compared. The CT staging was correlated with the surgico-pathologic results. RESULTS: The overall accuracy of CT for staging gallbladder cancers was 71%; it was 79% for T1 and T2 tumors, 46% for T3 tumors, and 73% for T4 tumors. For all three readers, the poorest accuracy was obtained in T3 tumors. No statistically significant difference was noted in the accuracy between the groups undergoing conventional CT and dynamic helical CT. A statistically significant difference was noted in the accuracy for staging thickened wall and intraluminal mass types of tumors (p<0.05); the highest accuracy was obtained in the intraluminal mass type (89%) and the massive type (83%), while it was 54% in the thickened wall type. CONCLUSION: The accuracy of tumor staging with CT in patients with gallbladder cancer depends on the morphological type of tumor. The poorest result is obtained in the thickened wall type.

Adult↗

Triplet superconductivity in an organic superconductor probed by NMR Knight shift.

The nature of the superconducting state in quasi-one-dimensional organic conductors has remained controversial since its discovery. Here we present results of (77)Se NMR Knight shift (K(s)) experiments in (TMTSF)(2)PF(6) under 7 kbar of pressure with a magnetic field aligned along the most conducting a axis. We find no noticeable shift in K(s) upon cooling through the superconducting transition. Since K(s) directly probes the spin susceptibility chi(s), the fact that chi(s) remains unchanged through the superconducting transition strongly suggests spin-triplet superconductivity.

Journal Article↗

Thermodynamic second law in irreversible processes of chaotic few-body systems.

Irreversible processes of few hard-ball (N) mechanical systems are investigated numerically and compared with the theoretical results of quasistatic processes. The thermodynamic second law is valid for N>or=2 for both equilibrium and nonequilibrium systems if the average ensemble of the large number of identical systems is taken.

Journal Article↗

Extreme genetic diversity among Pirital virus (Arenaviridae) isolates from western Venezuela.

Pirital-like virus isolates from rodents collected in a variety of habitats within a six-state area of central Venezuela were analyzed genetically by amplifying a portion of the nucleocapsid protein gene using RT-PCR. Comparisons of the sequences from 30 selected Pirital-like virus isolates demonstrated up to 26% divergence in nucleotide sequences and up to 16% divergence in deduced amino acid sequences. Within the Pirital monophyletic group, 14 distinct lineages or genotypes, differing by at least 6% in nucleotide sequences, were identified. Although sample sizes were small for some lineages, many of the different genotypes were sampled in only one region or locality, suggesting allopatric divergence. Complement fixation tests with representatives of the most divergent Pirital virus lineages failed to delineate multiple species or subtypes within the Pirital clade. These results indicate that the previously proposed 12% nucleocapsid protein amino acid sequence divergence cutoff value for delineating arenavirus species is not appropriate for the entire family. When individual clones were examined from PCR amplicons, a mean of 0.17% sequence diversity vs the consensus sequences was detected, suggesting diverse quasispecies populations within infected rodent hosts. Possible explanations for the extreme genetic diversity within and among Pirital virus populations in infected rodents are discussed.

Animals↗

Chaoslike behavior in nonchaotic systems at finite computation precision.

The dynamical behavior of a two-dimensional map is investigated numerically. A chaoslike behavior, i.e., a nonsmooth distribution of the attractor and seemly sensitive dependence of the motion on initial condition is found as the system state is nonchaotic (both Lyapunov exponents are nonpositive). The key point for this strange behavior is that the mode corresponding to the second negative Lyapunov exponent contains positive local Lyapunov exponent segments. It is argued that this kind of behavior may be typical and easily observed in practical numerical computations and experiments where small noise is inevitable.

Journal Article↗

Line emission in single-bubble sonoluminescence.

We report that single-bubble sonoluminescence (SBSL) at low light intensities produces emission bands similar to multibubble sonoluminescence (MBSL) for pure noble gas bubbles. A smooth crossover between SBSL and MBSL behavior can be induced by varying the acoustic pressure amplitude and thereby the intensity of the light emitted. The relative intensity of the band emission depends both on the molecular weight of the noble gas and the water temperature. Our results provide a connection between the mechanisms SBSL and MBSL and show that molecular emission plays a role in SBSL.

Journal Article↗

Development of expression systems for the production of recombinant human serum albumin using the MOX promoter in Hansenula polymorpha DL-1.

To optimize the secretory expression of recombinant human serum albumin (HSA) under the control of methanol oxidase (MOX) promoter in the methylotrophic yeast Hansenula polymorpha DL-1, we analyzed several parameters affecting the expression of HSA from the MOX promoter. Removal of the 5'-untranslated region derived from HSA cDNA in the expression cassette led to at least a fivefold improvement of HSA expression efficiency at the translational level. With the optimized expression cassette, the gene dosage effect on HSA expression was abolished and thus, a single copy of the expression vector integrated into the MOX locus became sufficient for the maximal expression of HSA. Northern blot analysis revealed that the levels of HSA transcript did not increase any further upon increasing copy number. The mox-disrupted (mox Delta) transformant was constructed, in which the genomic MOX gene was transplaced with the HSA expression cassette, to examine the effect of the methanol oxidase-deficient phenotype of the host on HSA expression. The mox Delta transformant showed higher levels of HSA production in shake-flask cultures than the MOX wild-type transformant, especially at low concentrations of methanol and a twofold higher specific HSA production rate in fed-batch fermentation with an abrupt induction mode. The native prepro signal sequence of HSA secreted in H. polymorpha was correctly processed and the mature recombinant protein had a pI value identical to that of the authentic HSA. Our results suggest that the H. polymorpha expression systems developed in this study are suitable for large-scale production of recombinant albumin.

5' Untranslated Regions↗

Reproducibility of scanning laser polarimetry (GDx) of peripapillary retinal nerve fiber layer thickness in normal subjects.

PURPOSE: To assess the reproducibility of measurement of retinal nerve fiber layer (RNFL) thickness among subjects using the GDx Nerve Fiber Analyzer (NFA). METHODS: One eye of each of five young and healthy volunteers was imaged by three newly trained technicians (R.-H.P, K.-R.K., and S.-T.K.). Each volunteer was scanned six consecutive times for five independent times within a 1-month period. One composite image was selected out of three best images per session. Intra- and interoperator reproducibilities were calculated and the influence of placement of measurement ellipse by a single operator on interobserver reproducibility was also investigated. RESULTS: Mean coefficients of variation for total integral value of RNFL were 3.67 +/- 1.47%, 3.86 +/- 2.13%, and 4.16 +/- 1.97%, respectively for the three technicians. Interoperator variability was not statistically significant (P = 0.075), and the difference was even less if a single ellipse drawn by one operator was used in all measurements (P = 0.1528) by repeated-measures analysis of variance (ANOVA). CONCLUSIONS: The results suggest that GDx NFA may provide acceptable intraoperator as well as interoperator reproducibility among Asian eyes.

Adult↗

Supranormal differential renal function is real but may be pathological: assessment by 99m technetium mercaptoacetyltriglycine renal scan of congenital unilateral hydronephrosis.

PURPOSE: It is unclear whether supranormal differential renal function of the hydronephrotic kidney is real or artifactual. We investigated the effect of clinical and renographic parameters on differential renal function. MATERIALS AND METHODS: The study included 34 males and 10 females from 1 to 9 months old (median age 2.6 months) with unilateral congenital hydronephrosis. A 99mtechnetium (Tc) mercaptoacetyltriglycine (MAG3) scan was performed, and regions of interest were drawn on the kidneys, and perirenal and lateral backgrounds. Differential renal function was calculated with and without background subtraction at 30-second intervals from 0.5 to 3 minutes after injection of 99mTc-MAG3. The effects of age, sex, obstruction, site and size of the hydronephrotic kidney were analyzed using the generalized estimating equations method. RESULTS: There were 11 right and 33 left hydronephrotic kidneys. An obstructive renographic pattern was present in 33 cases. The trends of differential renal function according to intervals were different between kidneys with and without background subtraction, and differential renal function increased significantly as size increased (p <0.05). Differential renal function of the hydronephrotic kidney with an obstructive renographic pattern increased with time when perirenal or no background subtraction was applied (p <0.05). The effects of age, sex or laterality on differential renal function were not significant. Supranormal function (differential renal function 55% or greater) was present regardless of background subtraction methods and measurement time. CONCLUSIONS: Differential renal function is higher in larger hydronephrotic kidney but function of the kidney with an obstructive pattern is overestimated on later phases of 99mTc-MAG3 renal scan. Supranormal differential renal function is real and may be pathologic since it is prone to occur in larger obstructive hydronephrotic kidneys.

Diuretics↗