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Biomedical subjects

M S Chang

Publications and source records attributed to M S Chang.

At least 91 records · Page 5Linked to original sources

Is 8-mm more effective than 4-mm tip electrode catheter for ablation of typical atrial flutter?

BACKGROUND: The prospective, randomized study comparing 4- with 8-mm tip electrodes for radiofrequency linear ablation of typical atrial flutter is not available. METHODS AND RESULTS: A total of 104 consecutive patients with typical atrial flutter were randomly assigned to undergo radiofrequency linear ablation using a 4- (Group I, n=54) or 8-mm tip electrode (Group II, n=50) catheter (temperature-control model, preset 70 degrees C). If complete bidirectional isthmus block could not be achieved after 5 pulses, the ablation catheter was changed to the other type; the maximal radiofrequency pulse number was limited to <10 pulses. Complete or incomplete isthmus conduction block was assessed by activation sequence in a multielectrode Halo catheter during low lateral right atrial and proximal coronary sinus pacing. Before shifting to the other catheter type, the 8-mm electrode catheter achieved higher complete isthmus block rate (92% versus 67%, P<0.05) with fewer pulses (2+/-1 versus 3+/-1, P<0.05), shorter procedure time (24+/-15 versus 31+/-12 minutes, P<0.05), and shorter fluoroscopic time (14+/-10 versus 23+/-15 minutes, P<0.05). After 5 failed ablation pulses, 12 (67%) of 18 patients in group I attained complete isthmus block by using an 8-mm tip catheter, but none of 4 patients in group II achieved complete block by changing to a 4-mm tip catheter. CONCLUSIONS: The 8-mm tip electrodes are more effective than the standard 4-mm length electrodes in linear ablation for typical atrial flutter. This clinical benefit may be of particular value for some patients with broad and/or thick isthmus.

Aged↗

Effects of radiofrequency catheter ablation on quality of life in patients with atrial flutter.

The long-term effects of radiofrequency catheter ablation on quality of life in patients with typical atrial flutter are still unknown. This study included 100 consecutive patients with clinically documented typical atrial flutter. Subjective perception of quality of life was assessed by a semiquantitative questionnaire before, and 1 and 6 months after ablation. Ablation of typical atrial flutter was associated with a significant improvement in the general quality of life, frequency of significant symptoms, and symptoms during attacks. The frequency of hospital admission and emergency room visits, and number of antiarrhythmic drugs significantly decreased after ablation. Activity capacity significantly improved after ablation in patients with depressed left ventricular function. All improvements after ablation were maintained over 6-month follow-up. However, patients with atrial fibrillation compared with those without atrial fibrillation before ablation had less improvement in the general quality of life, frequency of significant symptoms, and symptoms during attacks (including palpitation, asthenia, effort, dyspnea, rest dyspnea, and dizziness). Furthermore, patients with atrial fibrillation before ablation needed more antiarrhythmic drugs, and had a higher frequency of hospital admission and emergent room visits at 6-month follow-up (all variables p <0.01). Multivariate analysis demonstrated that only the presence of atrial fibrillation before ablation could independently predict improvement in general quality of life (p = 0.03), frequency of significant symptoms (p = 0.03), symptoms during attacks (p = 0.04), and decrease in the consumption of health care resources including antiarrhythmic drugs (p = 0.01), hospital admission (p = 0.02), and emergency room visits (p = 0.02). Ablation of typical atrial flutter could significantly improve quality of life, but patients who had atrial flutter associated with atrial fibrillation before ablation had less improvement than those without atrial fibrillation.

Activities of Daily Living↗

Targeting expression with light using caged DNA.

In this report, we describe the inactivation and site-specific light induction of plasmid expression using a photosensitive caging compound. Plasmids coding for luciferase were caged with 1-(4, 5-dimethoxy-2-nitrophenyl)diazoethane (DMNPE) and transfected into approximately 1-cm diameter sites of the skin of rats with particle bombardment. Skin sites transfected with caged plasmids did not express luciferase. However, subsequent exposure of transfected skin sites to 355-nm laser light induced luciferase expression in proportion to the amount of light. Liposome transfection of HeLa cells with DMNPE-caged green fluorescent protein (GFP) plasmids showed similar results. Caging DNA with DMNPE blocks expression at the level of transcription, since in vitro production of mRNA from linearized GFP plasmid was also blocked by caging and subsequently restored by exposure to light. Under the reaction conditions of these experiments, our absorbance data indicate that each DMNPE-caged GFP plasmid contains approximately 270 caging groups. In addition to inhibition and subsequent restoration of plasmid bioactivity, the presence and photocleavage of this relatively small number of cage groups also alters electrophoretic mobility of plasmids and optical absorption characteristics. This light-induced expression strategy provides a new means to target the expression of genetic material with spatial and temporal specificity.

Animals↗

Induction of the rat Cu/Zn superoxide dismutase gene through the peroxisome proliferator-responsive element by arachidonic acid.

The Cu/Zn superoxide dismutase (SOD1) catalyzes the dismutation of superoxide radicals produced from biological oxidation and environmental stresses. From the sequence analysis of transcription factor binding sites, the peroxisome proliferator-responsive element (PPRE) was located between nt -797 and -786 of the 5'-flanking sequence of the SOD1 gene. A promoter region was fused to a chloramphenicol acetyl-transferase gene, and the resultant construct was transiently transfected into HepG2 cells. The expression of the SOD1 gene was induced by arachidonic acid (AA). Functional analyses of the PPRE site by deletion, mutations, and the heterologous promoter system confirmed the induction of the SOD1 gene by AA through the PPRE site. Gel mobility shift assays showed AA inducible binding of the peroxisome proliferator-activated receptor (PPAR) to the PPRE. The intensity of PPAR binding was also increased by the treatment of retinoic acid (RA) and 9-cis retinoic acid (9-cis RA). These results suggest that the PPRE participates in the induction of the rat SOD1 gene by the peroxisome proliferator.

Animals↗

Differential coronary microvascular function in patients with left ventricular dysfunction of unknown cause--implication for possible mechanism of myocardial ischemia in early stage of cardiomyopathy.

To evaluate whether or not coronary microvascular dysfunction is associated with exercise-induced myocardial ischemia in left ventricular dysfunction of unknown cause, both the treadmill exercise test (TET) and coronary hemodynamics were studied in 20 patients with impaired left ventricular ejection fraction (<50% by radionuclide ventriculogram), normal cardiac size, normal coronary angiogram and no evidence of clinical heart failure. Ten subjects with atypical chest pain were studied as the control. Coronary hemodynamics were studied both at baseline and after dipyridamole infusion (0.56mg/kg, i.v. for 4'). There was no difference in age, gender, blood pressure, baseline great cardiac venous flow (GCVF) and coronary vascular resistance between ten patients with a positive TET and the other ten with a negative TET. At baseline, coronary sinus oxygen concentration was increased and myocardial oxygen consumption reduced in patients with a positive TET compared with those with negative a TET. After dipyridamole infusion, maximum GCVF (102+/-47 vs. 144+/-31 ml/min, P=0.027) and coronary flow reserve (2.31+/-0.49 vs. 3.00+/-0.61, P=0.012) were significantly reduced and minimum coronary vascular resistance was higher (1.00+/-0.42 vs. 0.63+/-0.12 mmHg/ml/min, P=0.016) in patients with a positive TET than in those with a negative TET. At follow-up, 40% of patients with a positive TET and 10% of those with a negative TET developed clinical heart failure with a dilated left ventricle during a period of 45 months. Thus, coronary microvascular function is heterogeneous in patients with left ventricular dysfunction of unknown cause. In some of them, coronary microvascular dysfunction could be related to the presence of exercise-induced myocardial ischemia, suggesting that similar pathophysiology underlies the early stage of dilated cardiomyopathy and syndrome X.

Adult↗

HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma.

Using the palindromic PCR-cDNA display method, we have cloned a novel gene overexpressed by human colon carcinoma relative to normal colon. Among normal tissues examined, only testis expresses it at a high level. Sequence analysis revealed its extensive homology with checkpoint genes rad17 of Schizosaccharomyces pombe and RAD24 of Saccharomyces cerevisiae. This novel gene designated as hRad17 is localized to chromosome 5q12,13.1, a region known to be deleted in a variety of human cancers. Promoter region and one pseudogene of hRad17 have been identified. Whereas the increased expression of hRad17 by human colon carcinomas may be related to the known resistance of these cells to DNA-damaging agents during therapy, the deletion of hRad17 in a variety of cancers may predispose them to increased rate of mutation and heightened sensitivity to DNA-damaging agents, including radiation and anticancer drugs.

Animals↗

Positive and negative regulatory elements in the upstream region of the rat Cu/Zn-superoxide dismutase gene.

Cu/Zn-superoxide dismutase (SOD1) catalyses the dismutation of superoxide radicals and neutralizes the oxidative effects of various chemicals. Deletion analysis of the upstream region of the rat SOD1 gene revealed that the promoter contains a positive regulatory element (PRE) and a negative regulatory element (NRE), which encompass the regions from -576 to -412 and from -412 to -305 respectively from the site of initiation of transcription. These DNA elements showed enhancer and silencer activities respectively in the natural context and in a heterologous promoter system. Using an electrophoretic-mobility-shift assay and a supershift assay with a specific antibody, the cis-elements of the PRE and NRE were identified as binding sites for transcription factors Elk1 and YY1 (Ying-Yang 1) respectively. Consistent with the presumed roles of the PRE and NRE, Elk1 increased SOD1 gene transcription about 4-5-fold, whereas YY1 exerted a negative effect of about 6-fold. Mutations of the Elk1- and YY1-binding sites led to diminution and elevation respectively of transcriptional activities, both in the natural context and in heterologous promoter systems. These results suggest that the transcription factors Elk1 and YY1, binding in the PRE and NRE respectively, co-ordinate the expression of the SOD1 gene.

Animals↗

Regional differences in the recovery course of tachycardia-induced changes of atrial electrophysiological properties.

BACKGROUND: Regional differences in recovery of tachycardia-induced changes of atrial electrophysiological properties have not been well studied. METHODS AND RESULTS: In the control group (5 dogs), atrial effective refractory period (AERP) and inducibility of atrial fibrillation (AF) were assessed before and every 4 hours for 48 hours after complete atrioventricular junction (AVJ) ablation with 8-week VVI pacing. In experimental group 1 (15 dogs), AERP and inducibility of AF were assessed before and after complete AVJ ablation with 8-week rapid right atrial (RA) pacing (780 bpm) and VVI pacing. In experimental group 2 (7 dogs), AERP and inducibility of AF were assessed before and after 8-week rapid left atrial (LA) pacing and VVI pacing. AERP and inducibility and duration of AF were obtained from 7 epicardial sites. In the control group, atrial electrophysiological properties obtained immediately and during 48-hour measurements after pacing did not show any change. In the 2 experimental groups, recovery of atrial electrophysiological properties included a progressive recovery of AERP shortening, recovery of AERP maladaptation, and decrease of duration and episodes of reinduced AF. However, recovery of shortening and maladaptation of AERP and inducibility of AF was slower at the LA than at the RA and Bachmann's bundle. CONCLUSIONS: The LA had a slower recovery of tachycardia-induced changes of atrial electrophysiological properties, and this might play a critical role in initiation of AF.

Animals↗

Xenobiotic-responsive element for the transcriptional activation of the rat Cu/Zn superoxide dismutase gene.

Cu/Zn superoxide dismutase (SOD1) catalyzes the dismutation of superoxide radicals produced from biological oxidation and environmental stresses. A number of xenobiotics are toxic because they generate free radicals, such as superoxide and hydroxyl radicals, through a redox cycle. The xenobiotic responsive element (XRE) was located between the nt -268 and -262 region of the 5'-flanking sequence of the SOD1 gene. Functional analyses of this element by deletion, mutations, and heterologous promoter systems confirmed that the expression of the SOD1 gene was induced by a xenobiotic through the XRE. Gel mobility shift assays showed the xenobiotic inducible binding of the receptor-ligand complex to XRE. The cytoplasmic fraction from nontreated HepG2 cells also contains the factor as a cryptic form and prominently reveals its DNA-binding activity by incubation with betaNF in vitro. These results suggest that the XRE participates in the induction of the rat SOD1 gene by xenobiotics.

Animals↗

Transcriptional activation of Cu/Zn superoxide dismutase and catalase genes by panaxadiol ginsenosides extracted from Panax ginseng.

Superoxide dismutase (SOD) converts superoxide radical to H(2)O(2), which is in turn broken down to water and oxygen by catalase. Thus, SOD and catalase constitute the first coordinated unit of defence against reactive oxygen species. A wide variety of chemical and environmental factors are known to induce these antioxidant enzymes. Here, we examined the effect of ginseng saponins on the induction of SOD and catalase gene expression. To explore this possibility, the upstream regulatory promoter region of Cu/Zn superoxide dismutase (SOD1) and catalase genes were linked to the chloramphenicol acetyltransferase (CAT) structural gene and introduced into human hepatoma HepG2 cells. Total saponin and panaxatriol did not activate the transcription of SOD1 and catalase genes but panaxadiol increased the transcription of these genes about 2-3 fold. Among the panaxadiol ginsenosides, the Rb(2) subfraction appeared to be a major inducer of SOD1 and catalase genes. The specificity of the Rb(2) effect was further confirmed by time course- and dose-dependent induction experiments. These results suggest that the panaxadiol fraction and its ginsenosides could induce the antioxidant enzymes which are important for maintaining cell viability by lowering the level of oxygen radical generated from intracellular metabolism.

Carcinoma, Hepatocellular↗

Results of coronary stenting after delayed angioplasty of the culprit vessel in patients with recent myocardial infarction.

Little information is available concerning the effect of late coronary stenting in patients with recent myocardial infarction, especially long-term results. We retrospectively reviewed our results of 57 stent placements in 52 consecutive patients who received stents at an infarct-related lesion 24 hr to 30 days after an acute myocardial infarctions (median, 14 days). The average age was 67 years; 90% were male. Two patients who suffered from acute stent thrombosis received revascularization again and two early deaths were due to refractory cardiogenic shock before discharge. Mean patient clinical follow-up was 18.3 +/- 6.5 months. There were 1 subacute stent thrombosis, 1 cardiogenic death, and 10 patients (20.8%) in total suffering from angina class II to IV. Angiographic follow-up was performed in 36 patients (80%) at a mean of 7.5 +/- 3.1 months. Of these 36 patients, only 1 (3% of the total population undergoing follow-up angiography) had reocclusion at follow-up, but restenosis existed in 18 patients (50%). We conclude that there is still relatively high incidence of angiographic recurrence that is often silent in long-term follow-up, though the long-term result of late stenting in recent MI is low incidence of reocclusion.

Aged↗

Heavy metal-mediated activation of the rat Cu/Zn superoxide dismutase gene via a metal-responsive element.

The Cu/Zn superoxide dismutase (SODI) catalyzes the dismutation of superoxide radicals produced in the course of biological oxidations. When placed under the control of the rat SOD1 gene promoter and transfected into human HepG2 hepatoma cells, the activity of a chloramphenicol acetyltransferase reporter gene was found to increase three- to four-fold in the presence of heavy metals (cadmium, zinc and copper). Functional analysis of mutant derivatives of the SOD1 gene promoter and the use of a heterologous promoter system confirmed that the induction of the SOD1 gene by metal ions requires a metal-responsive element (MRE) located between positions -273 and -267 (GCGCGCA). It was also shown by gel mobility shift assays that an MRE binding protein is induced by the exposure of the human liver cell line HepG2 to heavy metals. These results suggest that the MRE participates in the induction of the SOD1 gene by heavy metals.

Animals↗

Reversal of atrial electrical remodeling following cardioversion of long-standing atrial fibrillation in man.

BACKGROUND: In animal studies, atrial fibrillation has been shown to shorten the atrial refractory period and impair its rate adaptation. However, little is known about the effects of chronic atrial fibrillation on atrial electrophysiology and its recovery course in humans. METHODS AND RESULTS: Nineteen patients, mean age 64 +/- 14 years, with chronic atrial fibrillation of more than six months duration were included in this study. All of them were successfully converted to sinus rhythm with an external defibrillator. Atrial effective refractory periods at right atrial appendage and distal coronary sinus were determined with five pacing cycle lengths (300, 400, 500, 600 and 700 ms) at 30 min after cardioversion and once a day for four days. The atrial conduction properties, including P wave duration of surface ECG, and right and left atrial conduction times, were also measured at the same time interval. Twenty age-matched patients without a history of atrial tachyarrhythmia were evaluated as controls. In comparison with controls, chronic atrial fibrillation significantly shortened the atrial effective refractory period, impaired its rate adaptation response, especially at distal coronary sinus, and depressed the conduction properties of atria. The atrial conduction properties did not change during the four-day follow-up period; however, the atrial effective refractory period was gradually prolonged and its rate adaptation response improved after restoration of sinus rhythm. CONCLUSIONS: In humans, chronic atrial fibrillation significantly shortened the atrial effective refractory period, and impaired its rate adaptation response. Restoration and maintenance of sinus rhythm could reverse these electrophysiological changes.

Aged↗

Agonist-directed signaling of serotonin 5-HT2C receptors: differences between serotonin and lysergic acid diethylamide (LSD).

For more than 40 years the hallucinogen lysergic acid diethylamide (LSD) has been known to modify serotonin neurotransmission. With the advent of molecular and cellular techniques, we are beginning to understand the complexity of LSD's actions at the serotonin 5-HT2 family of receptors. Here, we discuss evidence that signaling of LSD at 5-HT2C receptors differs from the endogenous agonist serotonin. In addition, RNA editing of the 5-HT2C receptor dramatically alters the ability of LSD to stimulate phosphatidylinositol signaling. These findings provide a unique opportunity to understand the mechanism(s) of partial agonism.

3T3 Cells↗

General pharmacological properties of YJA 20379-1, a novel proton pump inhibitor with antiulcer activities.

The general pharmacological properties of YJA 20379-1 (2-amino-4,5-dihydro-8-phenylimidazo[2,1-b]thiazolo[4,5-g]benzo thi azole), a novel proton pump inhibitor with antiulcer activities, were investigated in mice, rats, guinea pig and rabbits. YJA 20379-1 at oral doses of 50, 100 and 200 mg/kg did not affect the general behaviour, hexobarbital hypnosis, motor coordination and body temperature in mice. The drug does not have analgesic and anticonvulsant action at 200 mg/kg p.o. The locomotor activity was not affected at 100 mg/kg p.o., but at 200 mg/kg, the activity was suppressed. YJA 20379-1 (at 2 x 10(-4) g/ml) did neither produce any contraction nor relaxation of isolated organs such as rat fundus, rat uterus, guinea pig ileum and guinea pig vas deferens, and the drug did not antagonize the contractile response to several spasmogens, such as histamine, acetylcholine, serotonin and oxytocin, and the drug up to 200 mg/kg p.o. did not affect pupil size of mice. The intestinal propulsion in mice was not affected up to 200 mg/kg p.o. The gastric emptying in rats was not affected at 100 mg/kg p.o., even if retardation in gastric emptying occurred at 200 mg/kg. YJA 20379-1 did not show anti-inflammatory action nor did it affect urinary excretion up to 200 mg/kg p.o. From these results, it is suggested that YJA 20379-1 at the high dose of 100 mg/kg p.o. may not exert any adverse effects.

Analgesics↗

Early recurrence of atrial fibrillation after external cardioversion.

UNLABELLED: Early recurrence of atrial fibrillation (AF) has been reported to occur in a significant number of patients after internal cardioversion. However, information about early recurrence of AF after external cardioversion has never been reported. The present study was conducted to investigate the clinical and electrophysiological characteristics of early recurrence of AF and its role in failure of cardioversion in patients with chronic AF. METHODS AND RESULTS: The study included 50 consecutive patients, age 69+/-9, with a history of chronic AF for more than 3 months duration and electrical cardioversion. They were divided into two groups according to the presence (group 1) or absence (group 2) of early recurrence of AF. There were 13 (26%) patients in group 1 and 37 (74%) patients in group 2. The age, gender, duration of AF, left ventricular function, left atrial dimension, and underlying heart disease were similar between group 1 and 2. Forty-five patients were successfully converted to sinus rhythm with a mean energy of 158+/-57 . Among those who failed to be converted to sinus rhythm, 4 (80%) belonged to group 1 and 1 (20%) belonged to group 2. The early recurrences of AF were initiated with consecutive APDs; but the numbers of APD in the first 30 seconds after cardioversion were similar between group 1 and 2. However, the coupling interval of the second APD was shorter in group 1 than group 2 (188+/-22 vs 324+/-59 ms, P = 0.003). Nine of the 13 early recurrences were prevented by an increase of shock energy (n = 3) or intravenous amiodarone infusion (n = 6). There were no differences in duration of follow-up, recurrence rate, and time interval to recurrence between group 1 and group 2. Early recurrence of AF occurred in 26% of chronic AF patients who underwent external electrical cardioversion and was a major cause of failure in cardioversion. Early recurrence of AF was initiated by APDs with decreasing coupling intervals and could be prevented with an increase of shock energy or amiodarone.

Aged↗