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Biomedical subjects

M S Chang

Publications and source records attributed to M S Chang.

At least 217 records · Page 12Linked to original sources

Comparisons of oral propafenone and quinidine as an initial treatment option in patients with symptomatic paroxysmal atrial fibrillation: a double-blind, randomized trial.

OBJECTIVE: The main aim of the study was to evaluate the safety and efficacy of propafenone versus quinidine as an initial choice in treatment of symptomatic paroxysmal atrial fibrillation. DESIGN: The study consisted of a 3-month treatment with oral propafenone hydrochloride or quinidine sulphate in patients with paroxysmal symptomatic atrial fibrillation, according to a double-blind randomized system. SETTING: The study was performed in the out-patient clinic of university hospital. MAIN OUTCOME MEASURES: The effects of the two drugs on attack frequency, ventricular rate and symptoms of symptomatic paroxysmal atrial fibrillation. RESULTS: In the oral propafenone group (n = 48), two patients (4%) discontinued the treatment because of dizziness. In the 46 patients who continued the treatment, the attack frequency decreased from 11 +/- 3 times per week at baseline to 1 +/- 1 times per week after treatment (P < 0.01). Forty (87%) out of the 46 patients had effective response to oral propafenone (more than 75% reduction of symptomatic arrhythmic attacks) on a mean dose of 615 +/- 10 mg day-1; the decrease in attack frequency was from 10 +/- 3 to 1 +/- 1 times per week. Twenty-three (50%) patients were free from recurrence of symptomatic paroxysmal atrial fibrillation. Comparisons of symptom scores for patients (n = 23) with attacks of paroxysmal atrial fibrillation after oral propafenone treatment showed that there was a significantly lower symptom score of palpitation, asthenia, effort dyspnea, dizziness, rest dyspnea and chest oppression in attacks of paroxysmal atrial fibrillation after propafenone treatment (11.05 +/- 3.78 versus 7.60 +/- 3.46, P < 0.01). From the oral quinidine group (n = 48), two patients (4%) discontinued treatment because of gastrointestinal discomfort. In the 46 patients who continued the treatment, the attack frequency decreased from 11 +/- 4 times per week at baseline to 3 +/- 2 times per week after treatment (P < 0.01). Twenty-one (46%) out of the 46 patients had effective response to oral quinidine on a mean dose of 1067 +/- 462 mg day-1, with a decrease in attack frequency from 12 +/- 3 to 1 +/- 1 times per week. Only 10 (22%) patients were free from recurrence of paroxysmal atrial fibrillation. Comparisons of symptom scores for patients (n = 36) with attacks of paroxysmal atrial fibrillation after quinidine treatment showed that there was no significant decrease of symptom score in attacks of atrial fibrillation (10.65 +/- 3.92 versus 10.20 +/- 3.80, P = 0.57). Furthermore, the percentage decrease of ventricular rate during atrial fibrillation was significantly greater in patients with propafenone (-25 +/- 4% versus -8 +/- 3%, P < 0.01). CONCLUSIONS: Oral propafenone appeared to be more effective than quinidine in suppressing attacks and alleviating symptoms of paroxysmal atrial fibrillation.

Administration, Oral↗

Expression, characterization, and genomic structure of carp JAK1 kinase gene.

A 3.7-kb cDNA encodes the carp JAK1 kinase of 1,156 amino acid residues. The overall amino acid sequence identity between carp JAK1 and murine JAK1, JAK2, JAK3, and human TYK2 is 57%, 35.5%, 31.3%, and 42.4%, respectively. In addition, carp JAK1 shows higher sequence homology to mammalian JAK1 in both the kinase-like (JH2) and kinase (JH1) domains (approximately 70% identity). Therefore, carp JAK1 is a homolog of mammalian JAK1. To investigate the possible function of JH2 domain, full-length, and various truncated forms of carp JAK1 were produced in the baculovirus system. Our results demonstrate that c-JH1 and c-JH2 associate with each other and c-JH2 can be tyrosine-phosphorylated by c-JAK1 and by c-JH(1 + 2). The JAK1 gene was also isolated from a carp genomic library and characterized. This gene is divided into 24 exons spanning at least 31 kb of genomic DNA. Exon 1 contains the 5'-untranslated region and exon 2 contains the putative translation initiation site. The 2.5-kb DNA region upstream of the transcription initiation site contains numerous potential binding sites for transcription factors including NF-IL6, HNF-5, AP1, GHF-5, and E2A. When this DNA fragment was placed upstream of the chloramphenicol acetyltransferase (CAT) reporter gene and transfected into a carp CF cell line, it could drive the synthesis of CAT enzyme 16 times more efficiently than the promoterless pCAT-Basic. Deletion analysis defined a positive regulatory region between -1,023 and -528. A smaller region (-181 to +59) without any typical TATA-box sequences, G + C-rich sequences, or other binding sequences for known transcription factors still had promoter activity. Constructs without this region did not have detectable promoter activity. This suggests that this region of DNA may play an important role in the expression of carp JAK1 gene.

Amino Acid Sequence↗

Electrophysiologic characteristics and anatomical complexities of accessory atrioventricular pathways with successful ablation of anterograde and retrograde conduction at different sites.

INTRODUCTION: Catheter ablation may eliminate anterograde and retrograde accessory pathway conduction at closely adjacent but anatomically discrete sites. However, the mechanisms of this discrepancy, the electrophysiologic and anatomical characteristics, and information about systematic study from a large patient population are not available. The purpose of this study was to investigate the electrophysiologic characteristics and anatomical complexities of the accessory pathway in which anterograde and retrograde conduction was successfully ablated at different sites. METHODS AND RESULTS: Thirty-eight (10.9%) patients (19 men and 19 women; mean age 37 +/- 2.4 years) fulfilling the criteria of having separate ablation sites for anterograde and retrograde conduction were designated as group I, and the other 310 patients (215 men and 95 women; mean age 47 +/- 0.6 years) were designated as group II. The patients with right-sided free-wall pathways had the highest incidence (18.6%) of separate ablation sites. The anatomical distance between anterograde and retrograde directions (left anterior oblique view, 13 +/- 0.6 vs 8 +/- 0.9 mm, P < 0.01; right anterior oblique view, 17 +/- 0.6 vs 5 +/- 0.7 mm, P < 0.01), and incidence of conduction impairment in one direction after successful ablation of another direction (15% vs 78%, P < 0.05) differed significantly between left and right free-wall pathways. The mean distances obtained from left (7 +/- 0.4 vs 14 +/- 0.4 mm, P < 0.05) and right (7 +/- 1.1 vs 15 +/- 0.9 mm, P < 0.05) anterior oblique views were shorter in patients who had impairment of conduction properties than those in patients without impaired conduction after successful ablation of one direction. CONCLUSIONS: This study showed that anatomical and functional dissociation of the accessory pathway into anterograde and retrograde components was possible. Further study on the relation between electrophysiologic and pathologic characteristics would be helpful to confirm these findings.

Adolescent↗

Dimension and related anatomical distance of Koch's triangle in patients with atrioventricular nodal reentrant tachycardia.

INTRODUCTION: The dimension of Koch's triangle in patients with AV nodal reentrant tachycardia has not been well described. Understanding the dimension and anatomical distance related to Koch's triangle might be useful in avoiding accidental AV block during ablation of the slow pathway. The purposes of this study were to define the dimension of Koch's triangle and its related anatomical distance and correlate these parameters with the successful ablation sites in patients with AV nodal reentrant tachycardia. METHODS AND RESULTS: We studied 218 patients with AV nodal reentrant tachycardia. The distance between the presumed proximal His-bundle area and the base of the coronary sinus orifice (DHis-OS) measured in the right anterior oblique view was used to define the dimension of Koch's triangle. The distance of the proximal His-bundle recording site from the successful ablation site (DHis-Ab) and the distance as a fraction of the entire length of Koch's triangle (DHis-Ab/DHis-Os) were determined. The mean DHis-Os and DHis-Ab were 25.9 +/- 7.9 and 13.4 +/- 3.8 mm, respectively. DHis-Os negatively correlated with patient age (r = -0.41, P < 0.0001) and body mass index (r = -0.18, P = 0.004). Among the patients with successful ablation sites in the medial area, DHis-Os was longer (27.2 +/- 6.6 vs 24.6 +/- 8.4 mm, P < 0.005), DHis-Ab was similar (12.9 +/- 3.1 vs 13.9 +/- 4.0, P > 0.05) and DHis-Ab/DHis-Os was smaller (0.48 +/- 0.04 vs 0.74 +/- 0.11, P < 0.05). Furthermore, the patients with successful ablation sites in the medial location needed more radiofrequency pulse numbers than those in the posterior location (6 +/- 4 vs 4 +/- 3, P < 0.05). CONCLUSION: The site of successful slow pathway ablation was consistently about 13 mm from the site recording the proximal His-bundle deflection in patients with AV nodal reentrant tachycardia despite marked variability in the dimensions of Koch's triangle; therefore, patients with large triangles required ablation in the medial region rather than the posterior region. Care should be taken when delivering radiofrequency energy to the posteroseptal area in patients with shorter DHis-Os to avoid injury to AV node.

Adolescent↗

Temperature monitoring in radiofrequency catheter ablation of atrial flutter using the linear ablation technique.

INTRODUCTION: Information about temperature and impedance monitoring during radiofrequency catheter linear ablation of atrial flutter has not been reported. We proposed that a radiofrequency catheter ablation system using a closedloop temperature control model could decrease the incidence of coagulum formation and shorten the radiation exposure and procedure times compared with those found in a power control model. METHODS AND RESULTS: Forty patients (8 women and 32 men; mean age 64 +/- 7 years) with atrial flutter were referred for radiofrequency ablation. The patients were randomized into two groups: group I patients underwent radiofrequency catheter linear ablation of atrial flutter using a power control of energy output model; and group II patients underwent the closedloop temperature control model with a target electrode temperature of 70 degrees C. As compared with group II, group I patients had a higher incidence of coagulum formation (12% vs 2%, P < 0.05), temperature shutdown (11% vs 0%, P < 0.01), and impedance shutdown (16% vs 3%, P < 0.01), more radiofrequency applications (7 +/- 3 vs 4 +/- 2, P < 0.01), and longer procedure time (100 +/- 25 vs 75 +/- 23 minutes, P < 0.05) and radiation exposure time (31 +/- 10 vs 20 +/- 7 minutes, P < 0.05) required for successful ablation. Larger deviations of temperature (9.0 degrees +/- 2.4 degrees C vs 5.0 degrees +/- 1.2 degrees C, P < 0.0001) and impedance (9.2 +/- 2.6 omega vs 5.3 +/- 1.6 omega, P < 0.0001) were also found in group I patients compared with those in group II. CONCLUSIONS: This study demonstrated that a closed-loop temperature control model could facilitate the effects of radiofrequency catheter ablation of the atrial flutter circuit by decreasing coagulum formation, temperature and impedance shutdown, and procedure and radiation exposure times.

Adult↗

Validation of carotid artery tonometry as a means of estimating augmentation index of ascending aortic pressure.

Our objective was to validate a carotid artery tonometry-derived augmentation index as a means to estimate augmentation index (AI) of ascending aortic pressure under various physiological conditions. A total of 66 patients (50 men, 16 women; mean age, 55 years; range, 21 to 78 years; 44 in Taiwan and 22 in the United States) undergoing diagnostic catheterization were studied. Arterial pressure contours were obtained simultaneously from the right common carotid artery by applanation tonometry with an external micromanometer-tipped probe and from the ascending aorta by a micromanometer-tipped catheter at baseline (n = 62), after handgrip (n = 36), or after sublingual nitroglycerin administration (n = 17). The AI (expressed as percentage values) was calculated as the ratio of amplitude of the pressure wave above its systolic shoulder to the total pulse pressure. The carotid AI was consistently lower than the aortic AI, but the two were highly correlated at baseline and after both handgrip and nitroglycerin. Mean +/- SD and correlation coefficients were baseline (14 +/- 16, 28(+) +/- 17, .77), handgrip (18 +/- 19, 32(+) +/- 15, .86), and nitroglycerin (7 +/- 12, 18(+) +/- 13, .52). In addition, after adjusting for age, sex, height, blood pressure, heart rate, and study site, the changes of both AIs from baseline values with handgrip or nitroglycerin were highly associated such that the aortic AI could be approximated from the carotid AI with appropriate regression equations. The high correlations and predictable changes after interventions between the central AI and those estimated from noninvasive carotid tonometry suggest that this technique may have wide applicability for many cardiovascular studies.

Adolescent↗

Changes in cardiac autonomic activities in patients with syndrome X. A study of spectral analysis of heart rate variability.

The present study was designed to assess cardiac autonomic activities, coronary microvascular function, and their relationship in patients with syndrome X. Control of coronary blood flow is complex, and impaired coronary flow reserve has been attributed as the cause of myocardial ischemia in patients with syndrome X. It is unknown whether cardiac autonomic activities are altered in the presence of coronary microvascular dysfunction in patients with syndrome X. Eighteen patients with syndrome X were studied. Great cardiac vein flow was measured by the thermodilution method and the coronary flow reserve was determined by intravenous dipyridamole (0.56 mg/kg) infusion. Twenty-four-hour ambulatory electrocardiograms were obtained in a drug-free state. Another 14 age- and sex-matched normal subjects served as a control group. The amplitude (in ms) of ultralow (ULF), very-low (VLF), low (LF), and high (HF) frequency bands and total spectra of heart rate variability were measured for twenty-four-hour and every four-hour interval of the day.

Adult↗

Effects of right ventricular pacing on ventriculoatrial conduction and systemic venous responses in sick sinus patients.

This study was designed to assess the ventriculoatrial (VA) conduction and systemic venous responses to right ventricular pacing at different pacing rates and the feasibility of identifying patients prone to pacemaker syndrome by means of a Doppler and two-dimensional echocardiographic technique. Twenty-two sick sinus patients who received ventricular-demand permanent pacemakers constituted the study group. The proximal inferior vena cava (IVC) diameters were measured by two-dimensional echocardiography. Fourteen patients had VA conduction by preimplant electrophysiologic study or paced electrocardiogram (Group II), while the other 8 patients presented no VA conduction (Group I). Abnormal systolic retrograde flow in the hepatic vein following each paced beat could be demonstrated in those patients with VA conduction in the basal state. In the 8 patients without VA conduction, the IVC diameters were significantly increased during rapid right ventricular pacing in those with left ventricular dysfunction (n = 4) as compared with those with normal left ventricular function (n = 4) (% increment at 120 beats per minute.

Blood Flow Velocity↗

Paradox of accessory pathway block after radiofrequency ablation in patients with the Wolff-Parkinson-White syndrome.

Although pacing technique has demonstrated that the most common site of conduction block in a manifest accessory pathway (AP) was between the AP and the ventricle, most of the block sites have been found to be between the atrium and AP after successful radiofrequency ablation. Furthermore, the block site in a concealed AP after successful radiofrequency catheter ablation has not been reported in the literature, and comparisons between a manifest and concealed AP have not been performed. This study included 219 consecutive patients undergoing successful radiofrequency catheter ablation of a single AP. AP potential was recorded at the successful target site in 76 of 92 (82.6%) patients with manifest APs, and in 99 of 127 (77.9%) patients with concealed APs. All the left-sided APs (including left posteroseptal APs) were ablated by a ventricular approach, and right-sided APs (including anteromidseptal and right posteroseptal APs) were ablated by an atrial approach. The site of conduction block was determined by analyzing and comparing the local electrograms recorded before and after radiofrequency ablation at successful ablation sites. Conduction block of manifest APs was between the atrial-AP (A-AP) in 69 patients (75%) and between the AP-ventricle (AP-V) interface in 7 patients (7.6%), whereas the conduction block of concealed APs occurred between the AP-V in 90 patients (70.9%) and between the A-AP interface in 9 patients (7.1%). Neither the preablation electrogram nor electrophysiologic characteristics of APs predicted the site of conduction block. Furthermore, neither the location of the APs nor the position of the ablation catheter affected the block site. It was concluded that the most common site of conduction block during successful radiofrequency catheter ablation of a manifest and concealed AP was between the A-AP and AP-V interface, respectively, and the impedance mismatch theory explained only part of the findings.

Adult↗

Electrocardiographic and electrophysiologic characteristics of anteroseptal, midseptal, and para-Hisian accessory pathways. Implication for radiofrequency catheter ablation.

STUDY OBJECTIVE: To investigate the ECG characteristics, the electrophysiologic properties, and an effective radiofrequency catheter ablation technique in patients with septal accessory pathways. PATIENTS: Forty-six consecutive subjects with septal accessory pathways located in the anteroseptal, midseptal, and para-Hisian areas. DESIGN AND INTERVENTIONS: ECGs obtained during sinus rhythm and orthodromic tachycardia, conduction properties obtained from electrophysiologic study, and results of two different ablation techniques were analyzed. MEASUREMENTS AND RESULTS: (1) Twenty-four (52.2%) had manifest preexcitation and 15 (32.6%) had multiple accessory pathways; (2) midseptal pathways could be differentiated from anteroseptal and para-Hisian pathways by a negative delta wave in lead III and a biphasic delta wave in lead aVF during sinus rhythm, and a negative retrograde P wave in two inferior leads during orthodromic tachycardia; (2) midseptal pathways had better antegrade conduction properties and a significantly higher incidence (61.5%) of inducible atrial fibrillation; (4) radiofrequency catheter ablation using lower energy (20+/-6 W) had a comparable effect to ablation using higher energy (36+/-5 W), but without impairment of atrioventricular (AV) node conduction or development of AV block; and (5) during the follow-up period of 26+/-14 months (range, 5 to 54 months), three (6.5%) patients had recurrence. CONCLUSIONS: Midseptal accessory pathways had ECG and electrophysiologic characteristics that were distinctive from those of anteroseptal and para-Hisian pathways. Catheter ablation of these septal pathways using low radiofrequency energy was safe and effective.

Adolescent↗

Hemodynamic mechanism of vasovagal syncope.

Vasovagal syncope is a common clinical problem, however the hemodynamic mechanism is not clearly understood. The aim of the present study was to investigate the circulatory control mechanism of vasovagal syncope provoked by the head-up tilt test. Thirty two patients with recurrent unexplained syncope were studied using a head-up (60 degrees) tilt test. The electrocardiogram, arterial blood pressure, pulmonary arterial pressure and central venous pressure were monitored continuously, and the cardiac output was measured by the thermodilution method. Twenty patients (62.5%) had positive tilt test responses, of which 12 developed typical vasovagal syncope with marked hypotension and bradycardia; the others developed hypotension without bradycardia. There were five women and seven men with a mean age (+/- SD) of 53.3 +/- 15 years. The effect of head-up tilt resembled that of hypovolemia. The central venous pressure, pulmonary capillary wedge pressure and cardiac output declined with an increase of heart rate and systemic vascular resistance. However the mean blood pressure was maintained. During vasovagal syncope, the heart rate and blood pressure fell precipitously and significantly, the cardiac index was reduced from 2.22 +/- 0.43 to 1.51 +/- 0.32 liters/min/m2 (p value < 0.05) and the systemic vascular resistance index decreased from 3,689 +/- 859 to 1,999 +/- 543.9 dynes s cm5/m2 (p value < 0.05). The results of our study showed that both reduction of cardiac output and withdrawal of sympathetic vasoconstriction tone contribute to the development of hypotension in vasovagal syncope.

Adult↗

Coronary microvascular dysfunction is associated with ischemic-like electrocardiogram during exercise in patients with anginal chest pain and normal coronary angiograms.

To determine the possible mechanism of the ischemic-like electrocardiogram (ECG) during exercise in the presence of anginal chest pain and normal coronary angiograms, both a treadmill exercise test (TET) and coronary hemodynamic study were prospectively performed in 33 consecutive patients (18 females and 15 males, aged 48 +/- 10 years) with angina of unknown cause. Although baseline characteristics and coronary hemodynamics were similar between patients with (TET+, n = 17) and those without (TET-, n = 16) ischemic-like ECG during TET, effort angina was more frequently seen in the former group (p < 0.01). Compared to TET- patients, TET+ patients had a significantly lower maximum great cardiac vein flow (GCVF, 108.8 +/- 47.0 vs 146.4 +/- 23.4 ml/min, p = 0.007), higher minimum coronary vascular resistance (0.94 +/- 0.41 vs 0.61 +/- 0.09 mmHg/ml/min., p = 0.003), and lower corrected GCVF (GCVF/rate-pressure product, 0.0087 +/- 0.0036 vs 0.0125 +/- 0.0019, p = 0.001) after dipyridamole infusion (0.56 mg/kg for 4 min). Though coronary flow reserve was significantly lower in TET+ than in TET- patients (2.26 +/- 0.59 vs 3.08 +/- 0.48, p = 0.0001), myocardial oxygen consumption and myocardial efficiency (rate-pressure product/myocardial oxygen consumption) were still similar between these two groups after dipyridamole infusion. Thus, coronary microvascular dysfunction rather than altered cardiac metabolism could contribute to effort angina and ischemic-like ECG during exercise in patients with anginal chest pain and normal coronary angiograms.

Adult↗

Establishment of primary cell culture from stria vascularis explants. Morphological and functional characterization.

To provide the prerequisite for long-term study of the inner ear related to structural and functional integrity, tissue of stria vascularis with spiral ligament was isolated from Wistar rat cochleas and cultured using the explant-culture technique. The following culture media were used: EMEM with Hepes buffer, hydrocortisone (400 ng/ml), transferrin (5 micrograms/ml). triiodothyronine (10(-9) M), cholera toxin (10(-10) M), insulin (5 micrograms/ml), and epidermal growth factor (10 ng/ml). To characterize the cells growing out from the explant, immunofluorescence with cytokeratin (cytokeratin 18) and ultrastructural examination with SEM and TEM were performed. The marginal cell function was investigated by expression of Na+, K(+)-ATPase antisera against beta 2 subunit of rat Na+, K(+)-ATPase and P-NPPase. We were able to maintain the cultured cells for 3 weeks or more. Monolayered marginal cells were observed beyond 14 days in vitro and the expression of cytokeratin 18 was especially enhanced. The cultured marginal cells were almost identical to in vivo cells both as regards ultrastructural features and Na+, K(+)-ATPase activity. The present results suggest that the primary explant culture technique is a reliable in vitro model of strial marginal cells. However, establishment of the cell line is needed for long-term study.

Animals↗

Myocardial infarction with normal coronary artery after carbon monoxide exposure: a case report.

Carbon monoxide intoxication usually disturbs the normal human biochemical respiratory chain cascade from which high affinity of carboxyhemoglobin to oxygen causes ischemic insult to the human tissues and cells. Ubiquitous injuries to human cells have already been well documented for a long period of time. Here we reported a 42-year-old female who was sent to the medical emergent unit under the suspicion of carbon monoxide exposure mainly with neurologic deficits. Serum carboxyhemoglobin level was found to be 18%. Serial revolutional changes of serum CK level and ECG were noted. The echocardiogram showed hypokinesia of left ventricular apical lateral wall. Normal coronary arteriogram was found in later admission date. The patient received hyperbaric oxygen therapy and was discharged with residual psychotic symptoms. This report presented normal coronary arteriogram with serial EKG and biochemical changes in a victim of CO intoxication with evidence of myocardial infarction. Impaired oxygen delivery and disturbed intracellular mitochondrial metabolism were considered to be responsible for the ischemic insult associated with carbon monoxide exposure. The role of hyperbaric oxygen therapy was also discussed in this report; however, more experiences in application are needed to determine it's benefits for patients.

Adult↗

Accessory atrioventricular pathway at the antero-medial mitral annulus--electrophysiologic characteristics and radiofrequency catheter ablation: a case report.

Accessory atrioventricular (AV) pathway located at or near the region of aorta-mitral continuity has rarely been mentioned. This report describes one such case with a concealed accessory AV pathway at the anteromedial mitral annulus adjacent to aorta-mitral continuity. The location of the accessory pathway was confirmed by successful radiofrequency catheter ablation. This patient was a 26-year-old male. His 12-lead surface ECG showed no evidence of ventricular preexcitation during sinus rhythm. The earliest retrograde atrial depolarization recorded from the routine catheters was at the His bundle area during ventricular pacing and orthrodromic AV reentrant tachycardia; paradoxically, the earliest left-sided atrial activation recorded from the coronary sinus catheters was at the distal coronary sinus area. The unique retrograde atrial activation sequence over the left atrium and His bundle area was not true for patients with left lateral or anterolateral accessory pathway. During tachycardia, the local electrogram from the successful ablation site showed local VA fusion in the anteromedial mitral annulus. After delivering one pulse of radiofrequency energy (30W), the accessory AV pathway was successfully eliminated without complication. This report presents a concealed left-sided accessory AV pathway at an unusual location. It is very important to describe special electrophysiologic characteristics and ablation technique in this unusual accessory pathway to improve knowledge in the era of interventional electrophysiology.

Adult↗

Identification, molecular cloning, and distribution of a short variant of the 5-hydroxytryptamine2C receptor produced by alternative splicing.

The actions of the neurotransmitter 5-hydroxytryptamine (5-HT) (serotonin) are mediated by multiple receptor subtypes. One of the prominent serotonin receptors in the brain is the 5-HT2C receptor (5-HT2C-R). We report the occurrence of a second 5-HT2C-R transcript, first identified using S1 nuclease protection of total RNA isolated from the choroid plexus. Analyses of the distribution of these two RNAs revealed that the short form is expressed in the same structures as the 5-HT2C-R mRNA, including choroid plexus, striatum, hippocampus, hypothalamus, olfactory tubercles, and spinal cord. Cloning and sequence analyses revealed a second cDNA with a 95-nt deletion in the region coding for the putative second intracellular loop and the fourth transmembrane domain of the 5-HT2C-R. This deletion leads to a frameshift in the coding sequence and the introduction of a premature stop codon. The predicted truncated protein (5-HT2C-tr) contains 172 amino acids, with 153 residues at the amino terminus, identical to the 5-HT2C-R, and 19 carboxyl-terminal amino acids that are unique. Although antibodies specific to the 5-HT2C-tr protein showed that the truncated form is expressed in a transfected fibroblast cell model system, there was no serotonergic ligand binding activity or phosphoinositide hydrolysis. Analyses of the 5-HT2C-R gene revealed that the two transcripts arise from a single gene by differential splicing using alternative donor sites and a common 3'-splice acceptor. Polymerase chain reaction amplification of mouse and human brain cDNAs demonstrated the occurrence of the same splicing patterns in these species. Although this study demonstrates tissue-specific expression of two 5-HT2C mRNA splice variants in rat, mouse, and human, the significance of the truncated form in these three species remains to be established.

3T3 Cells↗

Transduction of human interleukin-9 receptor gene into human cord blood erythroid progenitors increases the number of erythropoietin-dependent erythroid colonies.

We constructed a retroviral vector, pLhIL-9RSN, containing CDNA encoding the human interleukin-9 receptor (IL-9R) along with a neomycin phosphotransferase gene (Neo). In order to study the biological effects of the IL-9R, high titer (1-5 x 10(5) CFU/ml) viral supernatant, generated from the packaging cell lines, ecotropic GPE86 and amphotropic PA317, was used to transduce the IL-9R gene into sorted populations of CD34++ CD33-cells from human cord blood which are highly enriched for erythroid progenitor cells (BFU-E). Colony formation by BFU-E transduced with the IL-9R gene and grown without selection in G418 and in the presence of erythropoietin (Epo) and interleukin (IL)-9 was significantly increased up to three-fold and the size of the erythroid colonies was significantly increased 50-100% compared to colony formation by mock virus transduced cells. Moreover, colony formation by IL-9R-transduced cells was more sensitive to stimulation with lower doses of IL-9 and Epo. Individual colonies formed with or without selection in G418 were evaluated. Proviral integration and mRNA expression were respectively assessed by polymerase chain reaction (PCR) and reverse transcriptase (RT) PCR analysis and were apparent in 93% and 84% of the G418-resistant colonies and 52% and 48% of the colonies grown in the absence of G418. Our study demonstrates that a functional human IL-9R gene can be efficiently transduced into human cord blood hematopoietic progenitors using retroviral vectors with increased cytokine-dependent erythroid colony formation.

Cell Division↗

Different exercise performance between aged patients with syndrome X and those with coronary artery disease.

BACKGROUND: Both patients with coronary artery disease (CAD) and those with syndrome X (anginal chest pain, exercise-induced myocardial ischemia, normal coronary angiogram and no evidence of coronary spasm) have ischemic electrocardiogram (ECG) during exercise. However, the difference of ECG change during treadmill exercise test in these two patient groups has rarely been studied. METHODS: In this prospective study, we evaluated and compared the changes of hemodynamics and 12-lead ECG during treadmill exercise test by modified Bruce protocol in 29 patients with syndrome X and 46 patients with CAD. RESULTS: As compared with CAD patients, syndrome X patients had significantly higher heart rate, higher systolic blood pressure and higher rate-pressure product at 1mm ST depression and peak exercise. The time to 1mm ST depression (304 +/- 128 vs 254 +/- 92 seconds, p = 0.06) and total exercise duration (463 +/- 108 vs 331 +/- 111 seconds, p < 0.001) were also longer in syndrome X than in CAD patients. However, coronary flow reserves, obtained from 20 syndrome X patients and 9 CAD patients, did not differ between both groups. (2.3 +/- 0.6 vs 2.5 +/- 0.6, p = NS) CONCLUSIONS: Patients with syndrome X had higher ischemic threshold and better exercise tolerance than CAD patients though coronary flow reserve was similar between them. During exercise, more work-load as well as metabolic demands was required for the development of similar degree of myocardial ischemia in these aged syndrome X patients as compared with CAD patients.

Aged↗