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Biomedical subjects

M K Chung

Publications and source records attributed to M K Chung.

At least 37 records · Page 2Linked to original sources

Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

Arabidopsis↗

Left ventricular diastolic dysfunction in lone atrial fibrillation determined by Doppler tissue imaging of mitral annular motion.

In this study, we sought evidence for an underlying atrial or ventricular myopathy in patients with paroxysmal lone atrial fibrillation using standard echocardiographic parameters in addition to Doppler tissue imaging of mitral annular motion. No impairment in atrial contractile function was found, but there was evidence for impaired diastolic function in these patients.

Adult↗

Embryo lethality and teratogenicity of a new fluoroquinolone antibacterial DW-116 in rats.

DW-116, 1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-l-piperazinyl)-1, 4-dihydro-4-oxoquinolone-3-carboxylic acid hydrochloride, is a newly developed fluoroquinolone antibacterial. The potential of DW-116 to induce developmental toxicity was, investigated in Sprague-Dawley rats. DW-116 was administered by gavage to pregnant rats from days 6 to 16 of gestation at dose levels of 0, 31.3, 125, and 500 mg/kg per day. All dams were subjected to caesarean section on day 20 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. At 500 mg/kg, toxic effects including clinical signs of toxicity, suppressed body weight and decreased food intake were found in dams. An increase in the resorption rate, a decrease in the litter size, a reduction in the fetal weight, and a decrease in the placental weight were also seen. In addition, various types of external, visceral, and skeletal malformations occurred at an incidence of 17.9, 74.2 and 8.3%, respectively. Characteristic malformations included oedema, cleft palate, dilated cerebral ventricle, hypoplasia of lung and ventricular septum defect. A dramatic increase in the incidence of skeletal variations (55.6%) and retardations (94.4%) and a decrease in the number of ossification centres of sternebra, metacarpals, metatarsals and sacrocaudal vertebra were also observed. At 125 mg/kg, a reduction in the placental weight and an increase in the incidence of skeletal variations were found. There were no signs of maternal toxicity or embryotoxicity at 31.3 mg/kg. These results indicate that the fluoroquinolone antibacterial DW-116 is embryotoxic and teratogenic at minimally maternally toxic dose and is minimally embryotoxic at nonmaternally toxic dose in rats.

Abnormalities, Drug-Induced↗

Ineffectiveness and potential proarrhythmia of atrial pacing for atrial fibrillation prevention after coronary artery bypass grafting.

BACKGROUND: Atrial pacing is often used empirically to suppress atrial ectopy and prevent atrial fibrillation after coronary artery bypass grafting. METHODS: To determine whether atrial overdrive pacing reduces atrial fibrillation and atrial ectopy after coronary artery bypass grafting, 100 patients were randomized to no atrial pacing (Control) versus AAI pacing at 10 beats/min or more above the resting heart rate (Paced), started by postoperative day 1 and continued through day 4. Major end points were new atrial fibrillation and frequency of atrial ectopy during the first 4 days after coronary artery bypass grafting. RESULTS: Atrial fibrillation occurred by day 4 in 13 of 51 (25.5%) Paced and in 14 of 49 (28.6%) Control patients, p = 0.90. Control patients who developed atrial fibrillation had significantly more atrial ectopy than those who did not. Atrial ectopy was paradoxically more frequent in the Paced group (2,106+/-428 versus 866+/-385 per 24 hours, p = 0.0001). Loss of capture, sensing, and consistent atrial pacing occurred frequently during atrial pacing. CONCLUSIONS: Contrary to prevailing opinion and practice, postoperative atrial overdrive pacing significantly increases atrial ectopy and does not reduce the likelihood of atrial fibrillation.

Adrenergic beta-Antagonists↗

An epidemiological study of enuresis in Korean children.

OBJECTIVE: To estimate the prevalence of enuresis in children of elementary school age, to evaluate the impact of enuresis on these children and their parents, and to identify the methods and effectiveness of managing enuresis. Subjects and methods A randomly selected cross-sectional study was conducted in one elementary school in each urban ward (nine schools) in Pusan, Korea. The parents of these 12 570 children aged 7-12 years were asked to complete questionnaires which included items about the presence and frequency of enuresis, its perceived impact and management. Enuresis was defined as an episode of wetting occurring at least once per month. RESULTS: The overall response rate to the questionnaire was 55.8% (girls 28.2%, boys 27.6%). The prevalence of nocturnal, diurnal and combined enuresis was 9.2%, 2.2% and 1.4%, respectively. The overall prevalence of enuresis declined with age from 20.4% at 7 years old to 5.6% at 12 years old; 342 (57.0%) parents and 318 (55. 6%) children were concerned about enuresis. The common self-help strategies were waking the child at night to void (38.1%) and restriction of water intake (25.7%). Of the enuretic children, only 13.7% had consulted a health worker. CONCLUSION: The prevalence rates for enuresis in Pusan are similar to those reported from European countries. Enuretic children and their parents were moderately concerned about enuresis and the parents primarily used self-management within the family.

Child↗

Cardiac surgery: postoperative arrhythmias.

Arrhythmias are common after surgery, particularly after cardiac surgery. Atrial fibrillation is the most common arrhythmia encountered postoperatively, although ventricular arrhythmias and conduction disturbances can also occur. Older age is the most consistent predictor of postoperative atrial arrhythmias. beta-adrenergic blockers, amiodarone, and sotalol are the most effective at preventing postoperative atrial fibrillation. Sustained ventricular arrhythmias in the recovery period after cardiac surgery warrant aggressive therapy, usually with an implantable cardioverter-defibrillator in the absence of reversible causes. Postoperative, nonsustained ventricular tachycardia in the setting of left ventricular dysfunction and ischemic coronary disease also usually warrants risk stratification and possible treatment, often with electrophysiologic testing and implantation of an implantable cardioverter-defibrillator, if sustained ventricular arrhythmias are induced. Transient bradyarrhythmias may be managed with temporary pacing wires placed at surgery, but significant and persistent atrioventricular block or sinus node dysfunction can occur and indicate a need for permanent pacing.

Algorithms↗

Atrial fibrillation early postoperatively following minimally invasive cardiac valvular surgery.

We report a cohort of our first 100 minimally invasive cardiac valvular operations matched 1:1 by age and valvular surgery type with patients undergoing a traditional midline sternotomy approach. The prevalence of postoperative atrial fibrillation among patients with minimally invasive procedures versus traditional midline sternotomy was 26.3% versus 38.0%, respectively (p = 0.08). Neither multiple logistic regression nor Kaplan-Meier distribution analysis identified differences in postoperative atrial fibrillation between the 2 surgical techniques.

Adult↗

Higher energy synchronized external direct current cardioversion for refractory atrial fibrillation.

OBJECTIVES: We sought to evaluate the safety and efficacy of higher energy synchronized cardioversion in patients with atrial fibrillation refractory to standard energy direct current (DC) cardioversion. BACKGROUND: Standard external electrical cardioversion fails to restore sinus rhythm in 5% to 30% of patients with atrial fibrillation. METHODS: Patients with atrial fibrillation who failed to achieve sinus rhythm after at least two attempts at standard external cardioversion with 360 J were included in the study. Two external defibrillators, each connected to its own pair of R-2 patches in the anteroposterior position, were used to deliver a synchronized total of 720 J. RESULTS: Fifty-five patients underwent cardioversion with 720 J. Mean weight was 117 +/- 23 kg (body mass index 48.3 +/- 4.1 kg/m2). Structural heart disease was present in 76% of patients. Mean left ventricular ejection fraction was 45 +/- 12%. Atrial fibrillation was present for over three months in 55% of the patients. Sinus rhythm was achieved in 46 (84%) of the 55 patients. No major complications were observed. No patient developed hemodynamic compromise and no documented cerebrovascular accident occurred within one month after cardioversion. Of the 46 successful cardioversions, 18 patients (39%) remained in sinus rhythm over a mean follow-up of 2.1 months. CONCLUSIONS: External higher energy cardioversion is effective in restoring sinus rhythm in patients with atrial fibrillation refractory to standard energy DC cardioversion. This method is safe and does not result in clinical evidence of myocardial impairment. It may be a useful alternative to internal cardioversion because it could be done within the same setting of the failed standard cardioversion and obviates the need to withhold protective anticoagulation for internal cardioversion.

Adult↗

Induction of cytotoxic T lymphocytes with peptides in vitro: identification of candidate T-cell epitopes in hepatitis B virus X antigen.

Cytotoxic T lymphocytes (CTL) have been suggested to contribute to viral clearance during hepatitis B virus (HBV) infection. To induce effective CTL against viral infection by peptide vaccination, it is essential to identify the epitope peptides recognized by CTL. Here, 15 peptide sequences that contain HLA-A2.1-restricted CTL binding consensus motif were identified on hepatitis B virus X (HBx) protein and synthesized for further characterization. In the binding assay, 8 of 15 synthetic peptides enhanced the expression of HLA-A2.1 molecules on the surface of T2 cells, a human transport-associated antigen processing-deficient cell line. This result implies that these eight peptides are able to bind to the HLA-A2.1 molecules. These peptides were further tested for their ability to activate CTL from peripheral blood mononuclear cells (PBMCs) isolated from HBV chronic carriers. Five of eight tested peptides activated PBMC-derived T cells, resulting in the lysis of the target T2 cells pulsed with the same peptide. Furthermore, the CTL responses to HBx antigen in HBV chronic carriers were shown to be polyclonal, multispecific, and mediated mainly by CD8+ T cells. In contrast, these responses were not detected in uninfected healthy blood donors. Although the five CTL epitope peptides identified in this study have not been proven to be the naturally processed epitopes in HBV-infected hepatocytes, they could be candidates for peptide-based immunotherapy against HBV infection.

Amino Acid Sequence↗

Effects of extracorporeal shock wave lithotripsy on tiered therapy implantable cardioverter defibrillators.

The effects of extracorporeal shock wave lithotripsy (ESWL) were tested on four advanced generation implantable cardioverter-defibrillators (ICDs) in vitro and in vivo in two patients. During in vitro testing, advancement of nonsustained episode counters occurred in one device, and a set screw and power source cell loosened in another, which was connected to an external power source. No arrhythmias occurred during in vivo procedures, but programmed parameters were reset and elective replacement indicated after one procedure. ESWL can be performed safely in selected patients with ICDs, but testing should be performed afterwards to confirm satisfactory function and component continuity.

Defibrillators, Implantable↗

Voltage-dependent sodium and calcium currents in acutely isolated adult rat trigeminal root ganglion neurons.

Voltage-dependent sodium (INa) and calcium (ICa) currents in small (<30 microM) neurons from adult rat trigeminal root ganglia were characterized with a standard whole cell patch-clamp technique. Two types of INa showing different sensitivity to tetrodotoxin (TTX) were recorded, which showed marked differences in their activating and inactivating time courses. The activation and the steady-state inactivation kinetics of TTX-resistant INa were more depolarized by about +20 and +30 mV, respectively, than those of TTX-sensitive INa. Voltage-dependent ICa was recorded under the condition that suppressed sodium and potassium currents with 10 mM Ca2+ as a charge carrier. Depolarizing step pulses from a holding potential of -80 mV evoked two distinct inward ICa, low-voltage activated (LVA) and high-voltage activated (HVA) ICa. LVA ICa was first observed at -60 to -50 mV and reached a peak at about -30 mV. Amiloride (0.5 mM) suppressed approximately 60% of the LVA ICa, whereas approximately 10% of HVA ICa was inhibited by the same concentration of the amiloride. LVA ICa was far less affected by the presence of external Cd2+ or the replacement of Ca2+ by 10 Ba2+ than HVA ICa. The omega-conotoxin GVIA (omega-CgTx), an N-type ICa blocker, suppressed approximately 65% of the whole cell HVA ICa at the concentration of 1 microM. The omega-CgTx-resistant HVA ICa was sensitive to nifedipine (10 microM), a dihydropyridine (DHP) calcium channel antagonist, which produced an additional blockade by approximately 25% of the drug-free control ( approximately 70% of the omega-CgTx-resistant ICa). The combination of 10 microM nifedipine and 1 microM omega-CgTx left approximately 13% of the drug-free control ICa unblocked. The DHP agonist S(-)-BayK8644 (5 microM) shifted the activation of the HVA ICa to more negative potentials and increased its maximal amplitude. Additionally, S(-)-BayK8644 caused the appearance of a slowed component of the tail current. These results clearly demonstrate that the presence of two types of sodium channels, TTX sensitive and resistant, and three types of calcium channels, T, L, and N type, in the small-sized adult rat trigeminal ganglion neurons.

Animals↗

Simultaneous determination of flupyrazofos and its metabolite 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole and flupyrazofos oxon in rat plasma by high-performance liquid chromatography with ultraviolet absorbance detection.

An isocratic high-performance liquid chromatography (HPLC) system with UV detection was developed for simultaneous determination of flupyrazofos and its metabolites, 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole and flupyrazofos oxon, in rat plasma. Optimal analytical conditions involved an analytical cartridge column consisting of a phenyl bonded phase, a mobile phase of 50 mM phosphate buffer (pH3.0)-acetonitrile (40:60, v/v) and a UV detection wavelength of 232 nm. Under these conditions the peaks of flupyrazofos and its metabolites were all well separated and the total time for complete separation was less than 12 min. The limit of quantitation was 40 ng/ml for flupyrazofos and 20 ng/ml for PTMHP. Recoveries from rat plasma were higher than 90%. Following intravenous administration of flupyrazofos, the method has been successfully applied in a toxicokinetic study in rats involving plasma samples. Therefore, the current method is a valuable analytical tool for investigating the metabolism and toxicokinetics of flupyrazofos.

Animals↗

Analysis of risk factors for development of atrial fibrillation early after cardiac valvular surgery.

Atrial fibrillation (AF) commonly develops after cardiac valvular surgery. The objective of this study was to identify risk factors for postoperative AF following valvular surgery. A cohort of 915 consecutive adult patients undergoing isolated valvular surgery with preoperative sinus rhythm was analyzed. Univariate and independent multivariate risk factors for postoperative AF were determined. A second cohort of 305 patients with the same inclusion criteria was used to validate the multivariate predictors. Patients studied had a mean age of 56.1 +/- 14.7 years, 57.9% were men, 79.6% had a normal left ventricular ejection fraction, and their mean left atrial size was 46.2 +/- 9.3 mm. The incidence of postoperative AF was 36.7%. Independent predictors of postoperative AF included: advanced age (odds ratio [OR] 1.506 per decade, 95% confidence interval, [CI] 1.35 to 1.68, p = 0.0001); mitral stenosis (OR 2.066, CI 1.21 to 3.52, p = 0.0077); left atrial enlargement (OR 1.468, CI 1.07 to 2.01, p = 0.0165); use of systemic hypothermia (OR 0.572, CI 0.422 to 0.776, p = 0.0003); and a history of cardiac surgery (OR 0.676, CI 0.465 to 0.981, p = 0.0393). Among these variables, advanced age, mitral stenosis, and left atrial enlargement were confirmed as independent risk factors in the validation cohort.

Atrial Fibrillation↗

Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats.

Increased intrahepatic resistance in cirrhotic livers is in part caused by increased vascular tone. Several morphological abnormalities have been described in the sinusoidal endothelial cells of cirrhotic livers, but the functional impact of these abnormalities on the intrahepatic vascular tone has not been studied. The aim of this study was to investigate the intrahepatic endothelial function and the role of nitric oxide (NO) with regard to vascular tone in cirrhotic livers. Isolated rat liver perfusions were performed in cirrhotic rats (induced by chronic carbon tetrachloride inhalation) and weight-matched normal controls. After preconstricting the intrahepatic microcirculation with methoxamine (10(-4) mol/L), response to cumulative doses of receptor-mediated endothelial agonist, acetylcholine (10(-7) mol/L-10(-5) mol/L), was obtained. In another series, response to the receptor-independent endothelial agonist, calcium ionophore A23187 (10(-7) mol/L and 3 x 10(-7) mol/L), was obtained in the absence and presence of Nomega-nitro-L-arginine (NNA) and indomethacin. In a third series of rats, nitrate and nitrite production was measured in the perfusate of perfused normal and cirrhotic livers. There was significantly less vasorelaxation in cirrhotic livers as compared with normal livers in response to acetylcholine and calcium ionophore A23187 (P < .0001). The impaired vasorelaxation was a result of a decrease in both NO-mediated and non-NO-mediated components of vasorelaxation. Cirrhotic livers from ascitic rats had significantly less vasorelaxation as compared with livers from nonascitic rats (P < .005). There was significantly less production of nitrates and nitrites in cirrhotic livers (P < .05). The liver microcirculation of cirrhotic livers is characterized by endothelial dysfunction that results in impaired release of endothelial relaxing factors including NO.

Acetylcholine↗

Synthetic peptides of human papillomavirus type 18 E6 harboring HLA-A2.1 motif can induce peptide-specific cytotoxic T-cells from peripheral blood mononuclear cells of healthy donors.

To identify cytotoxic T-cell (CTL) epitopes against human papillomavirus type 18 (HPV 18) E6 protein that might be useful for developing peptide-based vaccine against HPV 18 infection, 18 peptides which possibly contain CTL epitopes were selected on the basis of previously described human leukocyte antigen (HLA)-A2.1-binding motif and chemically synthesized. In the binding assay of the synthetic peptides, 8 out of 18 synthetic peptides enhanced the expression of HLA-A2.1 molecules on T2 cell surface, which implies that these peptides were able to bind the HLA molecules. Those peptides having good binding affinity to HLA-A2.1 were tested for their ability to activate CTLs which were isolated from peripheral blood mononuclear cells (PBMCs) of healthy blood donors and to kill the target T2 cells pulsed with the same peptide. Five out of eight tested peptides activated CTLs and killed the target cells.

Binding Sites↗

Is hospital admission for initiation of antiarrhythmic therapy with sotalol for atrial arrhythmias required? Yield of in-hospital monitoring and prediction of risk for significant arrhythmia complications.

OBJECTIVES: We sought to determine the yield of in-hospital monitoring for detection of significant arrhythmia complications in patients starting sotalol therapy for atrial arrhythmias and to identify factors that might predict safe outpatient initiation. BACKGROUND: The need for hospital admission during initiation of antiarrhythmic therapy has been questioned, particularly for sotalol, with which proarrhythmia may be dose related. METHODS: The records of 120 patients admitted to the hospital for initiation of sotalol therapy were retrospectively reviewed to determine the incidence of significant arrhythmia complications, defined as new or increased ventricular arrhythmias, significant bradycardia or excessive corrected QT (QTc) interval prolongation. RESULTS: Twenty-five patients (20.8%) experienced 35 complications, triggering therapy changes during the hospital period in 21 (17.5%). New or increased ventricular arrhythmias developed in 7 patients (5.8%) (torsade de pointes in 2), significant bradycardia in 20 (16.7%) (rate <40 beats/min in 13, pause >3.0 s in 4, third-degree atrioventricular block in 1, permanent pacemaker implantation in 3) and excessively prolonged QTc intervals in 8 (6.7%) (dosage reduced or discontinued in 6). Time to the earliest detection of complications was 2.1 +/- 2.5 (mean +/- SD) days after initiation of sotalol, with 22 of 25 patients meeting criteria for complications within 3 days of monitoring. Baseline electrocardiographic intervals or absence of heart disease failed to distinguish a low risk group. Multivariate analysis identified absence of a pacemaker as the only significant predictor of arrhythmia complications (p = 0.022). CONCLUSIONS: Because clinically significant complications can be detected with in-hospital monitoring in one of five patients starting sotalol therapy, hospital admission is warranted for initiation of sotalol. Patients without pacemakers are at higher risk for these complications.

Aged↗