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Biomedical subjects

Y T Lee

Publications and source records attributed to Y T Lee.

At least 55 records · Page 3Linked to original sources

Increased levels of tissue plasminogen activator antigen and factor VIII activity in nonvalvular atrial fibrillation: relation to predictors of thromboembolism.

INTRODUCTION: Given that nonvalvular atrial fibrillation (AF)-associated stroke can be either cardioembolic or atherothrombotic, we investigated the relationships between nonvalvular AF and hemostatic factors reflecting intrinsic thrombogenic and atherogenic potentials (tissue plasminogen activator [t-PA] antigen, plasminogen activator inhibitor-1, and factor VIII activity). We also evaluated the clinical applicability of these hemostatic factors by examining whether AF subjects with established clinical or echocardiographic predictors of thromboembolism had higher levels of these factors. METHODS AND RESULTS: Of the 3,212 participants of a Chinese population-based study, 53 subjects (1.7%) with AF were identified. Among the hemostatic factors measured, t-PA antigen (median 12.8 vs 8.1 ng/mL; P < 0.01) and factor VIII activity (median 155% vs 133%; P < 0.05) were significantly higher in AF subjects after adjustment for age and sex. In multivariate analysis, features independently associated with t-PA antigen levels were AF, sex, body mass index, systolic blood pressure, total cholesterol, triglycerides, and left ventricular systolic dysfunction. Features independently associated with factor VIII activity levels included AF, age, and total cholesterol. Levels of both t-PA antigen and factor VIII activity were primarily elevated in AF subjects with predictors of thromboembolism (age > 75 years, hypertension, diabetes, and left ventricular systolic dysfunction), whereas in AF subjects with no thromboembolic predictors, plasma levels of hemostatic factors examined were similar to those without AF. CONCLUSION: We demonstrated that nonvalvular AF was independently associated with increased peripheral levels of t-PA antigen and factor VIII activity. Levels of both hemostatic factors were primarily elevated in AF subjects with predictors of thromboembolism. Whether these hemostatic factors are independently predictive of future thromboembolic events in AF patients requires further investigation.

Adult↗

Is non-Helicobacter pylori, non-NSAID peptic ulcer a common cause of upper GI bleeding? A prospective study of 977 patients.

BACKGROUND: Non-Helicobacter pylori, non-NSAID ulcer is relatively common in Western countries. Whether it is a significant problem in the Orient is unclear. The aim of this study was to investigate the incidence of non-H pylori, non-NSAID ulcers presenting with GI bleeding. METHODS: A prospective study was done of 1675 consecutive patients presenting with upper GI bleeding over a period of 12 months. Upper endoscopy was performed with biopsy specimens taken from the antrum and body of the stomach for a biopsy urease test (BUT) and histology for detection of H pylori. Exposure to nonsteroidal anti-inflammatory drugs (NSAID) or aspirin within 4 weeks of hospitalization was carefully scrutinized. A 6-week course of treatment with an H2-receptor antagonist was prescribed for patients who did not use an NSAID and had a negative BUT result. Follow-up endoscopy was performed to confirm H pylori status with a BUT and histology. Positive histology at either initial or follow-up endoscopy was used as the standard for diagnosing H pylori infection. RESULTS: Among 977 patients who were found to have ulcer bleeding, 434 (44%) had exposure to aspirin or an NSAID. Of the 543 non-NSAID users, 431 (79.4%) had a positive BUT and 112 (20.6%) were BUT negative on initial endoscopy. Eighty-nine of 112 patients who were NSAID negative, BUT negative returned for follow-up endoscopy. Forty-nine of 89 (55.1%) were found to have a positive BUT and positive histology at follow-up endoscopy. Only 40 of 977 (4.1%) patients admitted with ulcer bleeding were confirmed to have non-H pylori, non-NSAID ulcers. CONCLUSIONS: Non-H pylori, non-NSAID bleeding ulcer is uncommon. A negative BUT is unreliable for exclusion of H pylori infection during the acute phase of ulcer bleeding.

Adolescent↗

Effect of gemfibrozil on the composition and oxidation properties of very-low-density lipoprotein and high-density lipoprotein in patients with hypertriglyceridemia.

Recent studies suggest that both oxidized very-low-density lipoprotein (VLDL) and oxidized high-density lipoprotein (HDL) may play a role in the pathogenesis of atherosclerosis. Gemfibrozil is widely used and is reported to decrease VLDL levels and increase HDL levels. The aim of this study was to investigate the effect of gemfibrozil on the chemical composition and oxidative susceptibility of VLDL and HDL and their relationship with atherosclerosis. Twenty patients with hypertriglyceridemia were treated with 300 mg gemfibrozil, 3 times daily, for 12 weeks. Venous blood samples were collected before treatment, at the end of treatment, and 4 weeks after the end of treatment. Gemfibrozil effectively lowered concentrations of plasma lipid, apolipoprotein (apo) B, and apo E. The lipid and protein content of VLDL were also decreased, but not by the same extent. The surface-to-core ratio and apo E/apo B ratio of VLDL particles were increased after gemfibrozil treatment. HDL(2) cholesteryl ester and HDL(3) apo A-II content were also increased. Gemfibrozil treatment lowered levels of lipid peroxides in both VLDL and HDL particles. The susceptibility of VLDL to oxidation was unchanged, whereas maximal peroxide production was decreased. The oxidative susceptibility of both HDL(2) and HDL(3) decreased with gemfibrozil treatment. These results indicate that after gemfibrozil treatment, VLDL and HDL particles in patients with hypertriglyceridemia are less atherogenic, which may explain why gemfibrozil treatment is beneficial in terms of coronary heart disease in hypertriglyceridemia.

Adult↗

Suppression of collagen-induced arthritis in rats by continuous administration of dae-bang-poong-tang (da-fang-feng-tang).

Although dae-bang-poong-tang (an herbal formula of 15 herbs)-treated rats exhibited a mild inflammation, the significant histological changes including a marked infiltration of inflammatory cells in the synovium and damaged articular cartilages were not observed. The staining abilities of the cartilage such as periodic acid Schiff s reaction in the interterritorial matrix of hyaline cartilage, alcian blue and aldehyde fuchsin staining in the capsule of chondrocytes and in the interterritorial matrix of articular cartilage and Con A, sWGA and BSL-1 affinities of chondrocytes tended to decrease in the rats with collagen-induced arthritis compared with normal rats. Decreased stainabilities and affinities were almost recovered in the dae-bang-poong-tang-treated rats. In the collagen-induced rats, iNOS expression in the synovial lining cells and subsynovial tissue were significantly increased and numerous strong immunoreactive cells were demonstrated in the subsynovial tissue. Somewhat decreased immunoreaction of iNOS was shown in the synovial lining cells and subsynovial tissue of dae-bang-poong-tang-treated rats. It was concluded that dae-bang-poong-tang showed a notable protection against histological changes and histochemical staining, and it acted as an inhibitor of iNOS expression. Dae-bang-poong-tang may be used as a complementary therapeutic agent to alleviate the rheumatoid arthritis.

Administration, Oral↗

Further characterization of apolipoprotein B genetic variations in Taiwanese.

Apolipoprotein B (apoB, protein; APOB, gene) is the main protein component of low-density lipoprotein (LDL) and plays an important role in blood lipid metabolism. Previously, we have reported four APOB coding regions, 5' signal peptide, and 3' repeat sequence polymorphisms in our population. In this report, we further characterize other APOB genetic variations. The results illustrate that the mutation frequencies for Arg3500Gln (1/846 alleles), Arg4019Trp (2/786 alleles), -265 C/T promoter region (0/264 alleles), and intron 2 A/G (0/450 alleles) are very low. Our population showed a frequency of 68.9% for the B4311 Ser allele. The B4311 Asn allele was associated with a higher apoB level than the Ser group (p < 0.05) in normal controls. In the normal controls, a higher B4311 Asn/Asn genotype frequency was found in the group with total cholesterol (TC) > 200 mg/dL and apoB concentration > 85 mg/dL than in the group with a TC < 200 mg/dL and apoB < 85 mg/dL (p = 0.03 for TC comparison).

Analysis of Variance↗

Hypoxia delays the intracellular Ca2+ clearance by Na+-Ca2+ exchanger in human adult cardiac myocytes.

Transient myocardial ischemia during cardiac surgery causes a loss of energy sources, contractile depression, and accumulation of metabolites and H+ ion resulting in intracellular acidosis. The reperfusion following ischemic cardioplegia recovers intracellular pH, activates Na+-H+ exchange and Na+-Ca2+ exchange transports and consequently produces Ca2+ overload, which yields cell death. Among the various Ca2+ entry pathways, the Na+-Ca2+ exchanger is known to play one of the major roles during the ischemia/reperfusion of cardioplegia. Consequently, information on the changes in intracellular Ca2+ activities of human cardiac myocytes via the Na+-Ca2+ exchanger is imperative despite previous measurements of Ca2+ current of human single myocytes. In this study, human single myocytes were isolated from the cardiac tissues obtained during open-heart surgery and intracellular Ca2+ activity was measured with cellular imaging techniques employing fluorescent dyes. We report that the Na+-Ca2+ exchanger of adult cardiac myocytes is more susceptible to hypoxic insult than that of young patients.

Adult↗

A young male patient with persistent fever due to tuberculous peritonitis.

Tuberculous peritonitis is an uncommon disease in Hong Kong. We report a case of tuberculous peritonitis in a young male. The patient presented with persistent fever and intermittent cough for 1 month, but had no gastrointestinal symptoms. It was only through detection of slight abdominal ascites that subsequent abdominal paracentesis and laparoscopic biopsy confirmed the diagnosis. Appropriate antituberculous treatment was prescribed. Progress was complicated by persistent fever and liver function derangement, successfully managed by careful titration of antituberculous medications.

Adult↗

Differential effects of cilostazol and pentoxifylline on vascular endothelial growth factor in patients with intermittent claudication.

Cilostazol is a new phosphodiesterase inhibitor with anti-platelet and vasodilatory properties. Cilostazol and pentoxifylline are the only two drugs that have been approved for the treatment of patients with intermittent claudication. However, the mechanisms by which exercise tolerance is improved remain unclear. Vascular endothelial growth factor (VEGF) is a potent endothelial mitogen that results in angiogenesis when overexpressed in human subjects. To assess the potential role of VEGF in the improvement in exercise tolerance, we investigated plasma levels of VEGF in 50 patients with intermittent claudication who were allocated randomly to groups receiving cilostazol (n=17), pentoxifylline (n=17) or placebo (n=16). Patients given either cilostazol or pentoxifylline showed a significant improvements in maximal walking distance compared with the placebo group (34 m and 33 m respectively, compared with 5 m; both P<0.05). Neither cilostazol nor pentoxifylline increased the ankle-brachial index after treatment. Circulating VEGF levels were increased (from 116+/-29 to 169+/-45 pg/ml; P=0.002), and the levels of VEGF were correlated significantly with exercise tolerance in a positive direction (r=0.88, P=0.004), in those patients treated with cilostazol that did not have diabetes mellitus. In contrast, VEGF levels remained stable after the administration of pentoxifylline. These findings suggest that VEGF may contribute to the cilostazol-related improvement in exercise tolerance in non-diabetic patients. However, pentoxifylline did not affect VEGF levels, although a similar improvement in maximal walking distance was achieved. Thus the mechanisms involved in the pentoxifylline-treated group were different from those in the cilostazol-treated group, and require further study.

Aged↗

Hypertension status is the major determinant of carotid atherosclerosis: a community-based study in Taiwan.

BACKGROUND AND PURPOSE: Extracranial carotid artery (ECCA) atherosclerosis has been associated with hypertension-related stroke. The present study was aimed at investigating the determinants of ECCA atherosclerosis in patients with hypertension in Taiwan. METHODS: The extent and severity of ECCA atherosclerosis were measured by high-resolution B-mode ultrasonography and expressed as maximal intima-media thickness (IMT) of the common carotid artery, ECCA plaque score, and carotid stenosis >/=50%. From July through December 1996, 263 hypertensive patients (146 with hypertension and 117 with borderline hypertension) and 270 normotensive adults from the Chin-Shan Community Cardiovascular Cohort participated in this study. Risk factors and ECCA atherosclerosis were stratified by the blood pressure status. RESULTS: A significant dose-response relationship was found between the status of hypertension and the severity of carotid atherosclerosis. Multivariate logistic regression models revealed that hypertension (including borderline), male gender, smoking, and age >/=65 years significantly increased the risk of thicker IMT. The risk of ECCA plaque score >6 increased significantly in conjunction with hypertension, age >/=65 years, left ventricular hypertrophy on ECG, and smoking. However, hypertension and smoking were the 2 evident determinants of carotid stenosis >/=50% after adjustment for other covariates. Compared with the normotensive subjects, the ORs (and 95% CIs) for the hypertensive patients to develop carotid atherosclerosis were 5.0 (3.0 to 8.4) indexed by maximal common carotid artery IMT >/=75th percentile, 3.7 (1.8 to 7.9) by ECCA score >6, and 4.8 (1.4 to 16.5) by carotid stenosis >/=50%. CONCLUSIONS: Hypertension strongly influence carotid atherosclerosis. Our findings reinforce the hypothesis that hypertension has a major role in the pathogenesis of atherosclerosis.

Adult↗

Ambulance utilization in metropolitan and rural areas in Taiwan.

BACKGROUND AND PURPOSE: Emergency medical services (EMS) have expanded rapidly in the Asian developing countries recently. However, the patterns of ambulance utilization in the rural and urban areas of these countries have not been thoroughly described. This study investigated the patterns of ambulance utilization in two urban areas and the larger rural area of Taiwan formerly designated Taiwan Province. METHODS: We studied a total of 304,368 ambulance missions during 1997 in Taiwan. We analyzed the differences in the characteristics of emergency calls and the interventions performed on the scene in two urban areas, Taipei City and Kaohsiung City, and in the rural area formerly designated Taiwan Province. RESULTS: The call volume and percentage of non-transport calls were higher in the more developed of the two urban areas, Taipei City, than in Kaohsiung (p < 0.01). The incidence of calls with trauma-related causes was higher in both urban areas. However, the percentage of calls placed for trauma-related reasons was higher in the rural area (p < 0.01). More calls for acute medical illness were placed in Taipei City (p < 0.01) than in the rural area. The number of interventions performed by ambulance staff was higher in Taipei City and Kaohsiung City than in the rural area (p < 0.01). The availability of acute illness management was generally lower than needed in all areas. CONCLUSIONS: Call volume and the number of interventions performed were higher in the urban area, whereas the percentage of trauma-related calls was higher in the rural area. These findings suggest that EMS use patterns in Taiwan are transitioning towards a pattern characteristic of a more developed country. The differences in ambulance utilization patterns must be considered in plans to further develop EMS services in these areas.

Ambulances↗

Components of insulin resistance syndrome in a community-based population assessed by log-linear models.

BACKGROUND AND PURPOSE: To investigate the clustering of insulin resistance syndrome with hyperinsulinemia, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hypertension, and obesity, we conducted this cross-sectional study and analyzed the patterns of conditional independence among these five elements. METHODS: Fasting insulin, lipid profiles, blood pressure, and anthropometric data from 2165 Taiwanese older than 35 years in the Chin-Shan community were examined. The cut-off points of these five factors (all binary variables) were defined. The hierarchical log-linear regression with nested effects model was applied to fit this higher-order contingency table of five variables, and likelihood ratio (chi2) statistics were used to test the goodness of fit. RESULTS: Hyperinsulinemia was independently correlated with obesity (odds ratio [OR] 5.7, 95% confidence interval [CI] 4.5-7.3), low HDL (OR 2.3, 95% CI 1.8-2.9), and hypertriglyceridemia (OR 1.6, 95% CI 1.2-2.2). Hypertriglyceridemia was significantly associated with low HDL (OR 3.6, 95% CI 2.7-4.8), and non-significantly associated with hypertension (OR 1.3, 95% CI 0.9-1.7) and obesity (OR 1.1, 95% CI 0.8-1.6). In persons with normal triglyceride levels, hypertension was positively associated with obesity (OR 2.8, 95% CI 2.1-3.7) and low HDL (OR 2.0, 95% CI 1.5-2.8). Analyses from forward and backward selection methods gave similar results. Graphical models with conditional independence relationships among these five variables were demonstrated. CONCLUSIONS: The components of insulin resistance syndrome have intricate relationships. Hyperinsulinemia was most related to obesity, and hypertriglyceridemia was most related to low HDL.

Adult↗

Mutagenesis studies on the sensitivity of Escherichia coli acetohydroxyacid synthase II to herbicides and valine.

Acetohydroxyacid synthase (EC 4.1.3.18, also known as acetolactate synthase) isoenzyme II from Escherichia coli is inhibited by sulphonylurea and imidazolinone herbicides, although it is much less sensitive than the plant enzyme. This isoenzyme is also unusual in that it is not inhibited by valine. Mutating S100 (Ser(100) in one-letter amino acid notation) of the catalytic subunit to proline increases its sensitivity to sulphonylureas, but not to imidazolinones. Mutating P536 to serine, as found in the plant enzyme, had little effect on the properties of the enzyme. Mutating E14 of the regulatory subunit to glycine, either alone or in combination with the H29N (His(29)-->Asn) change, did not affect valine-sensitivity.

Acetolactate Synthase↗

Effects of methionine-induced hyperhomocysteinemia on endothelium-dependent vasodilation and oxidative status in healthy adults.

BACKGROUND: Homocysteine-mediated endothelial dysfunction has been proposed to occur via oxidative stress mechanisms in humans. However, there is controversy regarding the effects of homocysteine on endothelial function and oxidative status, which may in part result from age discrepancy across the studies. The present study was designed to investigate the aging effect on the relationship between endothelium-dependent vasodilation and oxidative status in methionine-induced hyperhomocysteinemia. METHODS AND RESULTS: Plasma homocysteine, phosphatidylcholine hydroperoxide (PCOOH), P-selectin levels, and brachial artery flow-mediated vasodilation were measured at baseline and 4 hours after an oral methionine load (0.1 g/kg) in 15 younger (21 to 40 years) and 15 older (55 to 70 years) healthy adults. Homocysteine increased from 7.3+/-1.3 micromol/L at baseline to 22.7+/-5.2 micromol/L at 4 hours in younger (P<0.001) and from 7. 4+/-1.4 to 24.3+/-4.5 micromol/L in older adults (P<0.001). PCOOH levels were not significantly different between baseline and 4 hours in both groups (P=0.10 in young; P=0.14 in old). P-selectin, which is expected to increase during oxidative stress, was not changed in older (P=0.08) but decreased in younger adults (P=0.037) at 4 hours. Flow-mediated vasodilation was preserved from 13.1+/-2.1% at baseline to 13.5+/-2.8% at 4 hours in younger (P=0.49) and decreased from 12.8+/-2.4% to 8.5+/-2.8% in older adults (P<0.001). CONCLUSIONS: The present study demonstrates that endothelial dysfunction caused by methionine-induced hyperhomocysteinemia is age-related and is mediated through impaired nitric oxide activity without change of oxidative status. Our data do not support previous hypotheses that endothelial damage by homocysteine is via oxidative stress mechanism in humans.

Adult↗

Oxidized low-density lipoproteins inhibit endothelial cell proliferation by suppressing basic fibroblast growth factor expression.

BACKGROUND: Hyperlipidemia inhibits proliferation of endothelial cells (ECs) in culture and angiogenesis in vivo and in arterial explants. Elucidation of the mechanisms may suggest novel therapies against atherosclerosis. METHODS AND RESULTS: Basic fibroblast growth factor (bFGF) expression and mitogenic effects were assessed in bovine aortic ECs incubated with oxidized LDL (ox-LDL). Compared with native LDL and lipoprotein-free controls, ox-LDL reduced bFGF mRNA levels in a time- and concentration-dependent manner, 100 microg/mL producing a maximum reduction of 40% to 50% within 24 to 48 hours. There were commensurate reductions in intracellular and extracellular bFGF concentrations, DNA and total RNA syntheses, and cell replication. FGF receptor 1 and beta-actin mRNA levels were unchanged. Ox-LDL accelerated bFGF mRNA degradation in actinomycin D-treated cells. However, inhibition of bFGF expression by ox-LDL was attenuated by cyclohexamide, indicating a requirement for continuous new protein synthesis for posttranscriptional destabilization. Reduced syntheses of DNA and total RNA were completely restored by bFGF but not by vascular endothelial growth factor. Inhibition of total RNA synthesis achieved by exposing cells to a bFGF-neutralizing antibody was similar in magnitude to that induced by ox-LDL. CONCLUSIONS: Cytotoxic effects of ox-LDL on ECs are attributable in part to suppression of bFGF expression.

Animals↗

A convenient method for oxidation of organophosphorus pesticides in organic solvents.

Since organophosphorus pesticides can be oxidized to oxons in vivo and in the environment and their determination based on inhibition of cholinesterases can be more sensitive after their oxidation to oxons, development of an efficient method for their in vitro oxidation is important for their toxicological and analytical studies. This study demonstrated that treatment of organophosphorus pesticides with 10 molar excess bromine in acetonitrile is a rapid and efficient method for their oxidation. For the nine organophosphorus pesticides tested, the reaction was complete within a few seconds. All reactions gave the respective oxons as single major product, except that of fenthion, which gave two major products, the respective oxon and another product from further oxidation of the oxon. The yields of the oxons were 82-100%. The inhibitory power of the pesticides on acetylcholinesterase before and after oxidation was measured and, for all pesticides tested, the power after oxidation was much higher than that before oxidation. Inhibition calibration curves for both unoxidized and oxidized forms of fenitrothion and parathion were obtained. The sensitivity of the detection of these pesticides was much higher after oxidation.

Environmental Pollutants↗

Cardioprotective effects of 17 beta-estradiol produced by activation ofmitochondrial ATP-sensitive K(+)Channels in canine hearts.

We have previously demonstrated the effects of estrogen on modulation of myocardial ATP-sensitive K(+)(K(ATP)) channel. Previous studies have demonstrated that activation of mitochondrial K(ATP)channel is a major contributor of ischemic cardioprotection. The purpose of the present study was to investigate the role of K(ATP)channel in estrogen-induced myocardial protection after ischemia/reperfusion in dogs. Anaesthetized dogs were subjected to 60 min of left anterior descending coronary artery occlusion followed by 2 h of reperfusion. In a first study to characterize effects of sex and the dose-response profile of estrogen on infarct size, the drug was intravenously administered at 10 or 20 microg/kg. In a second study to investigate the cardioprotective mechanisms of estrogen, vehicle, preconditioning or 17 beta -estradiol (10 microg/kg) was given, beginning 15 min prior to the 60 min occlusion period in the presence or absence of 5-hydroxydecanoate (5-HD). In the first study, administration of 17 beta -estradiol resulted in a significant, dose-dependent limitation of infarct size. Estrogen administration provided myocardial protection of similar magnitude in both males and females. In the second study, infarct size in control animals averaged 39+/-5% of the risk region, compared with 14+/-5% of the risk region in estrogen-treated dogs and 6+/-5% of the risk region in preconditioning dogs (both P<0.0001 v controls). Pretreatment with 5-HD completely abolished preconditioning- and estrogen-induced cardioprotection. Estrogen limits myocardial infarction size resulting from coronary artery occlusion and reperfusion in a dose-dependent fashion, irrespective of gender difference. The infarct size-limiting effect of estrogen++ was abolished by 5-HD, suggesting that the cardioprotective effect of estrogen may result from activation of myocardial mitochondrial K(ATP)channels.

Adenosine Triphosphate↗

Unbalanced atrioventricular septal defect with parachute valve.

A 5-month-old male patient presented with right-dominant unbalanced atrioventricular septal defect and left-sided parachute valve, and underwent successful biventricular repair. Because of the presence of a small left ventricle, left atrium, and a single left papillary muscle, an additional orifice was created in the left-sided atrioventricular valve with artificial partitioning of the right-sided atrioventricular valve. There was no evidence of mitral stenosis or regurgitation on follow-up echocardiography.

Follow-Up Studies↗