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Biomedical subjects

C T Ting

Publications and source records attributed to C T Ting.

At least 19 recordsLinked to original sources

Genetic variation in the human urea transporter-2 is associated with variation in blood pressure.

The kidney, by regulating the volume of fluid in the body, plays a key role in regulating blood pressure (BP). The kidney uses primarily sodium and, to a lesser extent, urea to maintain the appropriate volume of fluid. Genetic variation in proteins that determine sodium reabsorption and excretion is known to significantly influence BP. However, the influence of genetic variation in urea transporters on BP has not been examined. We determined therefore whether nucleotide variation in the kidney-specific human urea transporter, HUT2, is associated with variation in BP. After determining the genomic structure of the coding sequence, seven single nucleotide polymorphisms (SNPs) were identified. Two of the SNPs result in Val/Ile and Ala/Thr amino acid substitutions at positions 227 and 357 in the HUT2 open reading frame, respectively. Another SNP is silent and four others are in introns or the 3' untranslated region. Over 1000 hypertensive and low-normotensive individuals of Chinese origin were typed for five of these SNPs using a high-throughput genotyping method. The Ile227 and Ala357 alleles were associated with low diastolic BP in men but not women, with odds ratios 2.1 [95% confidence interval (CI) 1.5-2.7, P < 0.001] and 1.5 (95% CI 1.2-1.8, P < 0.001), respectively. There was a similar trend for systolic BP, and odds ratios for the Ile227 and Ala357 alleles were 1.7 (95% CI 1.2-2.3, P = 0.002) and 1.3 (95% CI 1.1-1.6, P = 0.007), respectively, in men.

Blood Pressure↗

Incipient speciation by sexual isolation in Drosophila: concurrent evolution at multiple loci.

Drosophila melanogaster from Zimbabwe and nearby regions shows strong but asymmetric sexual isolation from its cosmopolitan counterparts. By creating stable chromosome-substitution lines, earlier studies were able to show that the two major autosomes have very large effects on both male mating success and female mating preference. In this study, we genetically dissect this sexual isolation by recombination analysis between a whole-chromosome substitution line (which carries a Zimbabwe-derived third chromosome) and a strain with seven visible markers on that chromosome. Four loci are responsible for male mating success and three others are found to control female mating preference. Because male and female traits are not closely linked, their strong association among isofemale lines is most likely a reflection of sexual selection in nature. The results suggest that a large number of behavioral loci may evolve concurrently in the incipient stage of speciation before other aspects of reproductive isolation (such as hybrid sterility) have become evident. The results shed light on the population genetic processes underlying the formation of nascent species, as well as modes of speciation.

Animals↗

Pulmonary veins and ligament of Marshall as sources of rapid activations in a canine model of sustained atrial fibrillation.

BACKGROUND: In dogs, chronic rapid pacing may result in sustained atrial fibrillation (AF). However, activation patterns in pacing-induced sustained AF are unclear. METHODS AND RESULTS: We induced sustained AF (>48 hours) in 6 dogs by rapid pacing for 139+/-84 days. We then performed computerized atrial epicardial mappings and recorded the activations in the ligament of Marshall (LOM) and the pulmonary veins (PVs). During AF, mean activation cycle length in the right atrial free wall (126+/-17 ms) was significantly longer than that in the left atrial free wall (96+/-5 ms, P:=0.006). In addition, mean activation cycle length in the left atrial free wall was significantly longer than that in the LOM (84+/-5 ms, P:<0.001), the left inferior PV (81+/-4 ms, P:=0.001), and the left superior PV (85+/-7 ms, P:=0.003). Similarly, the dominant frequency was highest in the LOM and the PVs (range 11.2 to 13.3 Hz), followed by the left and right atria (P:<0.001). In all dogs studied, rapid and complicated electrograms were consistently observed at the LOM and the PVs. During AF, both wandering wavelets and organized reentry were present. There were more wave fronts in the left atrium than in the right atrium (P:<0.001). CONCLUSIONS: In chronic pacing-induced sustained AF, the LOM and the PVs are the sources of rapid activations. The mechanism by which the left atrium activates faster and has more wave fronts than the right atrium may relate to the fact that the left atrium is closer to the sources of rapid activations.

Analysis of Variance↗

Relation between the rapid focal activation in the pulmonary vein and the maintenance of paroxysmal atrial fibrillation.

This case report describes a patient with drug refractory paroxysmal atrial fibrillation (PAF). Rapid focal activations with multiple sharp spikes were continuously identified inside the left superior pulmonary vein (PV) during sustained AF. Among seven episodes of AF, cessation of rapid focal activations coincided with the conversion of AF to flutter (n = 4) or immediate AF termination (n = 3). Guided by sharp spikes in the PV, abrupt termination of AF occurred during radiofrequency energy application. Conclusively, rapid focal activations inside the PV are critical in AF maintenance. Cessation of these rapid focal activations underlies the mechanism by which AF converts to flutter.

Adult↗

Sex in Drosophila mauritiana: a very high level of amino acid polymorphism in a male reproductive protein gene, Acp26Aa.

Many genes pertaining to male reproductive functions have been shown to evolve rapidly between species, and evidence increasingly suggest the influence of positive Darwinian selection. The accessory gland protein gene (Acp26Aa) of Drosophila is one such example. In order to understand the mechanism of selection, it is often helpful to examine the pattern of polymorphism. We report here that the level of amino acid polymorphism in the N-terminal quarter of Acp26Aa is high in Drosophila melanogaster and is unprecedented in its sibling species Drosophila mauritiana. We postulate that (1) this N-terminal segment may play a role in sperm competition, and (2) D. mauritiana may have been under much more intense sexual selection than other species. Both postulates have important ramifications and deserve to be tested rigorously.

Amino Acid Sequence↗

High-throughput genotyping with single nucleotide polymorphisms.

To make large-scale association studies a reality, automated high-throughput methods for genotyping with single-nucleotide polymorphisms (SNPs) are needed. We describe PCR conditions that permit the use of the TaqMan or 5' nuclease allelic discrimination assay for typing large numbers of individuals with any SNP and computational methods that allow genotypes to be assigned automatically. To demonstrate the utility of these methods, we typed >1600 individuals for a G-to-T transversion that results in a glutamate-to-aspartate substitution at position 298 in the endothelial nitric oxide synthase gene, and a G/C polymorphism (newly identified in our laboratory) in intron 8 of the 11-beta hydroxylase gene. The genotyping method is accurate-we estimate an error rate of fewer than 1 in 2000 genotypes, rapid-with five 96-well PCR machines, one fluorescent reader, and no automated pipetting, over one thousand genotypes can be generated by one person in one day, and flexible-a new SNP can be tested for association in less than one week. Indeed, large-scale genotyping has been accomplished for 23 other SNPs in 13 different genes using this method. In addition, we identified three "pseudo-SNPs" (WIAF1161, WIAF2566, and WIAF335) that are probably a result of duplication.

Alleles↗

Successful resuscitation of patient with massive coronary air embolism occluding two vessels during coronary angiography--a case report.

Massive coronary air embolism is usually disastrous although successful resuscitation has been reported previously. To what extent a patient with coronary air embolism can be resuscitated is not known. The authors report a rare case of massive air embolism to the left coronary arteries and successful resuscitation by vigilantly maintaining an effective driving force to dissipate the air lock.

Aged↗

Orbital adenocarcinoma of lacrimal gland origin in a dog.

A 13-year-old intact female mixed-breed dog was presented for a progressive enlargement of the right eye, which had been treated previously for conjunctivitis. A round, firm mass, approximately 4 cm in diameter, was protruding from the superotemporal aspect of the right orbit, displacing the eyeball anteriorly and ventromedially. The mass was encapsulated, distinct from the eyeball, and not associated with the eyelids. On cut surface, there was a pale multilobulated periphery, with a dark red, soft, and depressed core. Histologically, tumor cells formed cords and tubules, which were stained with mouse anti-human cytokeratin antibody AE1/AE3. Residual glands were serous, and the majority of tumor cells were negative for mucin. The supraorbital location, encapsulation, and residual serous glands suggest that this mass was a low-grade adenocarcinoma of the lacrimal gland.

Adenocarcinoma↗

The phylogeny of closely related species as revealed by the genealogy of a speciation gene, Odysseus.

Molecular differentiation between races or closely related species is often incongruent with the reproductive divergence of the taxa of interest. Shared ancient polymorphism and/or introgression during secondary contact may be responsible for the incongruence. At loci contributing to speciation, these two complications should be minimized (1, 2); hence, their variation may more faithfully reflect the history of the species' reproductive differentiation. In this study, we analyzed DNA polymorphism at the Odysseus (OdsH) locus of hybrid sterility between Drosophila mauritiana and Drosophila simulans and were able to verify such a prediction. Interestingly, DNA variation only a short distance away (1.8 kb) appears not to be influenced by the forces that shape the recent evolution of the OdsH coding region. This locus thus may represent a test case of inferring phylogeny of very closely related species.

Animals↗

Differential coronary hemodynamics and left ventricular contractility in patients with syndrome X.

The relationship between coronary hemodynamics and left ventricular contractility was studied in 20 patients with syndrome X. Among them, 10 patients with a resting left ventricular ejection fraction (LVEF, by radionuclide method) equal to or greater than the mean value of the whole group (58%) were defined as having relative increased left ventricular contractility (group H), and another 10 patients with relatively normal contractility (50%</=LVEF<58%) were in group N. Eight subjects with normal contractility, exercise test and coronary angiograms served as the control (group C). Baseline great cardiac venous flow (GCVF) was higher in group N than in group H (P<0.05) and C (P<0.05), but similar between group H and C. After dipyridamole infusion (0.56 mg/kg, i.v., for 4 min), maximum GCVF was less in group H than in group N (P<0.001) and C (P<0.001), but similar between group N and C. As compared to group C (3.09+/-0.35), coronary flow reserve was reduced in both group H (2.34+/-0.55, P=0. 004) and N (2.40+/-0.36, P=0.001). In all syndrome X patients, resting LVEF was negatively correlated to baseline GCVF (P=0.026) and tended to be positively correlated to baseline coronary vascular resistance (P=0.057). Thus, coronary hemodynamics was altered with left ventricular contractility in syndrome X patients. In these patients, coronary flow reserve was similarly reduced with different underlying mechanisms. The limited increase of GCVF after dipyridamole infusion suggests impaired coronary microvascular dilation capacity in patients with relatively increased left ventricular contractility and the increase of baseline GCVF in those with normal contractility is more likely due to an altered basal myocardial metabolism.

Adult↗

Significantly higher levels of oxidized LDL autoantibody in coronary artery disease patients.

BACKGROUND: Increasing evidence shows that oxidized low-density lipoprotein (ox-LDL) might play an important role in the pathogenesis of atherosclerosis. Ox-LDL is immunogenic and induces an autoantibody, which we used as a tool for measuring the content of ox-LDL in vivo. METHODS: Patients who were admitted for diagnostic cardiac catheterization for typical or atypical angina pectoris were enrolled in this study. After fasting for 12 hours, a venous blood sample was drawn from the antecubital vein for testing triglyceride, total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and ox-LDL autoantibody. The ox-LDL autoantibody was quantified using an enzyme linked immunosorbent assay. All patients underwent coronary angiography. Those who had more than 50% angiographic coronary luminal stenosis, were grouped into the coronary artery disease (CAD) group. RESULTS: Sixty-four patients were enrolled in the study (male/female = 46/18; mean +/- standard deviation, age, 64 +/- 9 years). The CAD group had a significantly higher level of ox-LDL autoantibody than the non-CAD group (494.0 +/- 355.0 mU/ml vs 258.1 +/- 196.8 mU/ml, p = 0.004). However, the other lipid profiles including triglyceride, total cholesterol, LDL-cholesterol and HDL-cholesterol were not statistically different between the two groups. Forty-six patients in this study had an arterial blood sample taken from the femoral artery for testing ox-LDL autoantibody. There was no significant difference between the arterial and venous samples of ox-LDL autoantibody (385.2 +/- 333.3 mU/ml vs 399.3 +/- 339.5 mU/ml, n = 46, p = 0.530). CONCLUSIONS: Ox-LDL autoantibody was significantly higher in the CAD group. Ox-LDL may prove to play a key role in the pathogenesis of atherosclerosis. Further study of Ox-LDL and its role in the process of atherosclerosis is warranted.

Adult↗

Catheter-induced coronary spasm--a view of mechanical factors and experience with selective left coronary arteriography.

BACKGROUND: Coronary spasm during cardiac catheterization is not unusual. The mechanism of spasm remains uncertain, but is considered to be multifactorial. Many researchers believe that coronary spasm that develops during catheterization is partly spontaneous and partly catheter-induced. Because catheter-induced spasm results from mechanical irritation, we tried to find the iatrogenic factors that predispose patients to coronary spasm during coronary angiography. METHODS: Retrospectively, we reviewed the records of 7,295 patients who underwent coronary angiography at our hospital from June, 1983 to November, 1997; coronary spasm was documented in 30 patients, who became the study group. We randomly selected 41 patients who had normal coronary arteries as the normal control group. After reviewing cine films of coronary angiography, we compared these two groups for several parameters. These parameters included the length and diameter of the left main coronary artery (LMC), the angle between the LMC and the aorta, the angle between the catheter tip and the LMC, whether the catheter tip came into contact with the vascular wall and whether there was vessel wall bulging, catheter size and catheter/LMC ratio. This angiographic data and the demographic features, including age, sex, history of hypertension, diabetes mellitus, smoking, previous myocardial infarction, family history of coronary artery disease, cholesterol and triglyceride levels and chest pain character (exertional or rest pain) were compared between the study patient group and the control group. RESULTS: The results disclosed that larger catheter size (7.1 +/- 0.6 mm vs 6.4 +/- 0.7 mm, p < 0.001), smaller LMC diameter (4.2 +/- 0.9 mm vs 4.9 +/- 1.0 mm, p = 0.004), larger catheter/LMC ratio (0.07 +/- 0.05 vs 0.05 +/- 0.03, p = 0.022), catheter contact with the vessel wall (27/30 vs 20/41, p < 0.001) and vessel bulging (18/30 vs 5/41, p < 0.001) were related to catheter-induced coronary spasm. We found that the catheter tip coming into contact with the vessel wall, vessel wall bulging and catheter/LMC ratio (odds ratio 8.92 x 10(14)) were statistically significant factors predisposing patients to catheter-induced coronary spasm. CONCLUSIONS: Multiple factors contribute to coronary spasm. Of those, mechanical or iatrogenic factors might predispose patients to spasm during coronary catheterization. These facts deserve our attention, because iatrogenically induced spasms may be avoided by meticulously selecting catheters and manipulating them gently.

Adult↗

Randomized, double-blind comparison of irbesartan and enalapril for treatment of mild to moderate hypertension.

BACKGROUND: Irbesartan is a newly developed angiotensin II receptor antagonist. Its antihypertensive efficacy and safety in Taiwanese patients with mild to moderate hypertension remains to be determined. METHODS: This was a multicenter, double-blind, randomized, parallel group study. One hundred and sixteen patients from three centers were enrolled. After a placebo lead-in period of 14 days, 55 patients (24-75 years-of-age) who had a mean seated diastolic blood pressure of 95 to 110 mmHg were randomized to once-daily treatment with irbesartan 150 mg or enalapril 10 mg. Doses were doubled at week 4 if trough seated diastolic blood pressure was 90 mmHg or more. Trough blood pressure was measured at zero, two, four and eight weeks of treatment. RESULTS: Both treatments lowered blood pressure with no significant difference in efficacy between treatment groups. Irbesartan 150 mg to 300 mg provided reductions in trough seated systolic and diastolic blood pressures at week 8 of -16.5 mmHg and -7.2 mmHg, respectively, with 36% of patients having a favorable response. Similarly, enalapril 10 mg to 20 mg reduced systolic and diastolic blood pressure by -10.6 mmHg and -5.0 mmHg, respectively, with a response rate of 43%. Headache, malaise and dizziness were the major adverse reactions observed in both groups. The incidence of drug-related cough was significantly higher with enalapril (18%) than with irbesartan (0%). CONCLUSIONS: Irbesartan 150 mg to 300 mg once daily was as effective in lowering blood pressure as enalapril 10 mg to 20 mg once daily. Both irbesartan and enalapril were well tolerated, while there was a significantly lower incidence of cough with irbesartan compared with enalapril.

Adult↗

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↗

Coronary artery aneurysms: A 25-patient study.

Coronary artery aneurysm is a rare disorder, characterized by abnormal dilatation of a localized portion or diffuse segments of the coronary artery. We studied clinical demographics, catheterization findings, and clinical outcomes in an Asian patient cohort with documented coronary artery aneurysms. Compared to a Caucasian adult population, our patient cohort had a lower incidence of coronary artery aneurysm (0.25% vs. 2.6%), and more patients with nonobstructive coronary artery aneurysms (70%); age, gender, and coronary distribution were comparable. The initial presentation of myocardial infarction occurred in five patients (5/17, 30%) with nonobstructive coronary artery aneurysms; however, none who were receiving preventive medications consisting of anticoagulant and antiplatelet agents subsequently developed myocardial infarction. We conclude that the incidence of coronary artery aneurysms with or without associated significant coronary stenosis seems to be lower in the Asian population. In contrast, the incidence of nonobstructive coronary artery aneurysms is considerably high and should not be thought of as a relatively benign disease entity if not treated with preventive medications. Rheumatoid arthritis-related vasculitis might be a cause of coronary artery aneurysm. Surgical intervention is based on the severity of coronary artery stenosis. The result of medical treatment has been compatible with long-term survival. Cathet. Cardiovasc. Intervent. 48:31-38, 1999.

Adult↗

Insulin-like growth factor I improves cardiovascular function and suppresses apoptosis of cardiomyocytes in dilated cardiomyopathy.

To investigate how insulin-like growth factor I (IGF-I) modulates cardiovascular function and myocardial apoptosis in heart failure, the therapeutic effects of IGF-I were determined in a canine model of dilated cardiomyopathy. The animals were paced at 220 beats/min, and the left ventricular (LV) chamber became dilated after 2 weeks. A subset of paced dogs was treated with s.c. injections of IGF-I from week 3 to week 4. After 4 weeks of pacing, untreated paced dogs developed significant ventricular dysfunction. IGF-I-treated paced dogs showed better cardiac output, stroke volume, LV end-systolic pressure, and LV end-diastolic pressure. Moreover, pulmonary wedge pressure and systemic vascular resistance were increased in the untreated group and decreased in the IGF-I-treated group. IGF-I treatment was associated with less thinning of the ventricular wall. Compared with the controls, untreated paced dogs showed increased apoptosis of cardiac muscle cells, which was partially suppressed by IGF-I treatment. The myocardial apoptotic index was negatively related to the thickness of the ventricular wall and to cardiac output, suggesting that ventricular remodeling/dysfunction involves the occurrence of myocardial apoptosis. Due to the close resemblance between this experimental model of dilated cardiomyopathy and human heart failure, the results of this study provide evidence that IGF-I may be a potential therapeutic agent for the failing human heart.

Animals↗