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ABSTRACT: The present study was carried out to investigate the protective effects of Danshen (DS, Salvia miltiorrhiza) on adriamycin (ADR)-induced cardiac and hepatic toxicity. Wistar rats were divided into six groups: control group, 10 animals received saline (i.p.); 15 animals received ADR (3 mg/kg, i.p.) three times weekly, for 2 weeks; 10 animals each received DS(1) (20 mg/kg, oral) and DS(2) (100 mg/kg, oral) for 30 days; 15 animals each received DS(1) + ADR and DS(2) + ADR. The ADR-induced cardiac and hepatic toxicity and protective action of DS were determined and quantitated with the use of hemodynamic measurements, biochemical analyses of serum, synthesis rates of DNA, RNA and protein, myocardial antioxidants, lipid peroxidation and histopathological procedure. Liver function was damaged. Nucleic acid as well as protein synthesis was inhibited, while lipid peroxidation was increased. Myocardial glutathione peroxidase (GSHPx) activity and superoxide dismutase activities (SOD) were decreased and histopathology revealed myocardial lesions indicative of ADR-induced cardiac and hepatic toxicity. In contrast, administration of DS before and concurrent with ADR significantly attenuated these effects. In conclusion, DS is potentially protective against ADR-induced cardiac and hepatic toxicity.
Phytotherapy Research 01/2008; 21(12):1146-52. · 2.09 Impact Factor
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Jane M Carlton,
Robert P Hirt,
Joana C Silva,
Arthur L Delcher,
Michael Schatz,
Qi Zhao,
Jennifer R Wortman,
Shelby L Bidwell,
U Cecilia M Alsmark,
Sébastien Besteiro, [......],
Steven L Salzberg,
Petrus Tang,
Cheng-Hsun Chiu, Ying-Shiung Lee,
T Martin Embley,
Graham H Coombs,
Jeremy C Mottram,
Jan Tachezy,
Claire M Fraser-Liggett,
Patricia J Johnson
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ABSTRACT: We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the approximately 160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.
Science 02/2007; 315(5809):207-12. · 31.20 Impact Factor
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ABSTRACT: Ulcerative colitis (UC) is a chronic inflammatory disorder primarily affecting the colon mucosa. Its etiology and pathogenesis remain unclear. We used 2-DE and MS to identify differentially expressed proteins among the UC active, UC inactive, nonspecific colitis, and normal colon mucosa. Thirteen down-regulated and six up-regulated proteins were identified. Of the down-expressed proteins, eight (heat-shock protein 90 (HSPA9B), heat-shock protein 60 (HSPD1), H+-transporting two-sector ATPase (ATP5B), prohibitin (PHB), mitochondrial malate dehydrogenase (MDH2), voltage-dependent anion-selective channel protein 1 (VDAC1), thioredoxin peroxidase (PRDX1), and thiol-specific antioxidant (PRDX2)) were mitochondrial proteins, three (ATP5B, MDH2, triosephosphate isomerase) were involved in energy generation, three (PRDX1, PRDX2, SELENBP1) were cellular antioxidants, and six (HSPD1, HSPA9B, PRDX1, PRDX2, PHB, VDAC1) were stress-response proteins. Transmission electron microscopy revealed pathological alterations of mitochondrial ultrastructures even before the global colonocyte changes in the UC colon mucosa. PHB, an essential mitochondrial component protein, was down-expressed in the disease active as well as inactive colon mucosa from the patients of UC, indicative of an early event of mitochondrial changes during UC development. In contrast, aberrant activation of NFAT and ectopic expression of potential immunogenic proteins (tumor rejection antigen 1 and poliovirus receptor related protein 1) were found in the UC-diseased colon mucosa. Our findings suggest the implications of colonocyte mitochondrial dysfunction and perturbed mucosa immune regulation in the pathogenesis of UC and provide potential targets for the development of a new therapy.
PROTEOMICS 11/2006; 6(19):5322-31. · 4.51 Impact Factor
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Lung-An Hsu,
Yu-Lin Ko,
Chi-Jen Chang,
Chiao-Feng Hu,
Semon Wu,
Ming-Sheng Teng,
Chun-Li Wang,
Wan-Jing Ho,
Yu-Shien Ko,
Tsu-Shiu Hsu, Ying-Shiung Lee
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ABSTRACT: Recently, a T/C polymorphism of the promoter region of the APOA5 gene at position -1131 and a G/T polymorphism at position 553 were found to be associated with increased levels of plasma triglyceride. Triglyceride plays a role in coronary artery disease (CAD), so this case-control study tested for a possible link between these two APOA5 polymorphisms, their common haplotypes and the risk of CAD. The subjects included 211 CAD patients and 677 unrelated controls. A significantly higher level of triglycerides and a lower level of high-density lipoprotein cholesterol (HDL-C) were noted for carriers with -1131C than for non-carriers (P<0.001 and 0.013, respectively) among controls. Plasma triglyceride levels were significantly higher (P=0.014) in controls with genotypes that contained the c.553T allele than in homozygotes for the G allele. Subjects homozygous for the wild-type haplotype had significantly lower triglyceride levels and higher HDL-C levels than subjects with all other haplotype pairs. The -1131C homozygous carriers and c.553T heterozygous carriers were found more frequently in 211 patients with CAD than in the 317 age/sex-matched controls (P=0.008 and 0.023, respectively) in univariate analysis. The significant association between c.553T allele carriers with CAD remained in multivariate regression analysis (OR, 1.79; CI, 1.07-3.00; P=0.028), after adjustments were made for other risk factors. Notably, haplotype analysis further verified that the APOA5 -1131C and c.553T bi-loci haplotype was significantly overpresented in CAD, as compared to the controls. These results indicate that the variants of APOA5 gene modulate plasma triglyceride and may use them to predict CAD susceptibility in Taiwanese Chinese.
Atherosclerosis 04/2006; 185(1):143-9. · 3.79 Impact Factor
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ABSTRACT: To determine the genetic risk factors for venous thromboembolism (VTE), this study examined 14 genetic variants from 10 hemostatic genes in 186 Taiwanese VTE patients and the same number of matched controls, which demonstrated FGA (encoding alpha fibrinogen) Thr312Ala polymorphism was the only variant significantly associated with VTE. Nine genetic polymorphisms on the fibrinogen cluster region of chromosome 4q28 were further studied, in which four FGA polymorphisms were found in strong linkage disequilibrium and were significantly associated with VTE by genotype and allele frequency analyses. Haplotype analysis showed significantly different FGA haplotype frequencies between VTE patients and controls with the haplotype F1, containing -1051G, -3A, 312Ala and TaqI duplication alleles, significantly associated with susceptibility to VTE (P = 0.001). Haplotype-pair analysis results also indicated a strong association of the haplotype-pair F1F1 with VTE in various VTE patient subgroups. In vitro functional analysis indicated that FGA -1051G, -3A and TaqI duplication alleles enhanced significantly the transcription level of FGA; however, control subjects with FGA genotypes containing these alleles had no elevated plasma fibrinogen levels. In conclusion, our experimental data indicated that functional genetic variants in FGA are risk factors for VTE in Taiwanese populations. Determination of FGA genotypes will likely contribute to primary prevention of this condition.
Human Genetics 04/2006; 119(1-2):84-91. · 5.07 Impact Factor
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ABSTRACT: The traditional Chinese medicine prescription "sheng-mai-san (SMS)" has been used for treating patients with coronary heart disease for a long time and was found to have antioxidative effects. Here, we applied adriamycin (doxorubicin, ADR), a highly effective anticancer agent, as an inducer to establish the animal model of dose-related cardiomyopathy due to inhibition of nucleic acid as well as protein synthesis, formation of free radicals, and lipid peroxidation. The objective of this study was to investigate the protective effects of SMS on adriamycin-induced cardiomyopathy. Wistar rats were divided into four groups: CONT (control), ADR, SMS, and ADR + SMS. ADR (cumulative dose, 15 mg/kg) was administered to rats in six equal intraperitoneal injections over a period of 2 weeks and SMS was administered via a feeding tube throughout the mouth once a day for 30 days (cumulative dose, 150 g/kg). At the end of the 5-week post-treatment period, the hearts of the rats were surgically removed for the study of synthesis rates of DNA, RNA and proteins. Besides myocardial antioxidants, lipid peroxidation and morphological ultrastructure were also evaluated. Three weeks after the treatment, cardiomyopathy and congestive heart failure were characterized according to assessment in ascites, congested liver, depressed cardiac function and myocardial cell damage. The results demonstrated that nucleic acid as well as protein synthesis was inhibited, while lipid peroxidation was increased. Myocardial glutathione peroxidase (GSHPx) activity was decreased and electron microscopic examination revealed myocardial lesion indicative of ADR-induced cardiomyopathy. In contrast, administration of SMS before and concurrent with ADR significantly attenuated the myocardial effects. It also lowered mortality as well as the amount of ascites. In addition, indexes in myocardial GSHPx, macromolecular biosynthesis and superoxide dismutase activities were increasing, with a concomitant decrease in lipid peroxidation and preserved myocardial ultrastructure. These results indicated that SMS may be partially protective against ADR-induced cardiomyopathy.
The American Journal of Chinese Medicine 02/2006; 34(2):295-305. · 1.98 Impact Factor
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ABSTRACT: We studied the electrophysiological and antiarrhythmic actions of HA-7 [N-benzyl-7-methoxy-2,3,4,9-tetrahydrofuro[2,3-b]quinoline-3,4-dione], a furoquinoline alkaloid derivative, in guinea pig heart preparations. In the perfused whole heart model, HA-7 caused a prolongation in the basic cycle length, ventricular repolarization time, and the atrioventricular (AV) nodal Wenckebach cycle length and prolonged the refractory period of the atrium, AV node, and His-Purkinje system. The atrioventricular conduction interval was also prolonged in a frequency-dependent manner. In isolated hearts, HA-7 significantly raised the threshold for experimental atrial fibrillation and reduced the occurrence of reperfusion-induced ventricular fibrillation. Conventional microelectrode-recording study shows that HA-7, but not d-sotalol, prolonged the action potential duration (APD) and decreased the maximum rate of depolarization in isolated atrial strips. In ventricular papillary muscles, higher concentrations of HA-7 caused a prolongation of APD(90) in a frequency-independent manner, whereas d-sotalol exerted a reverse frequency-dependent action on this parameter. Whole-cell patch clamp results on ventricular myocytes indicate that HA-7 decreased both the slow (I(Ks)) (IC(50) = 4.8 muM) and fast component (I(Kr)) (IC(50) = 1.1 muM) of the delayed rectifier K(+) currents. Similar results could also be observed in atrial myocytes. The inward rectifier K(+) current (I(K1)) was also reduced somewhat by HA-7. HA-7 also suppressed the Na(+) inward current (I(Na)) (IC(50) = 2.9 muM) and inhibited the L-type Ca(2+) current (I(Ca)) (IC(50) = 4.0 muM, maximal inhibition = 69%) to a lesser extent. We conclude that HA-7 blocks multiple ionic currents and that these changes affect the electrophysiological properties of the conduction system as well as the myocardial tissues and may contribute to its antiarrhythmic efficacy.
Journal of Pharmacology and Experimental Therapeutics 02/2006; 316(1):380-91. · 3.83 Impact Factor
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Yun-Shien Lee,
Chun-Houh Chen,
Angel Chao,
En-Shih Chen,
Min-Li Wei,
Lung-Kun Chen,
Kuender D Yang,
Meng-Chih Lin,
Yi-Hsi Wang,
Jien-Wei Liu,
Hock-Liew Eng,
Ping-Cherng Chiang,
Ting-Shu Wu,
Kuo-Chein Tsao,
Chung-Guei Huang,
Yin-Jing Tien,
Tzu-Hao Wang,
Hsing-Shih Wang, Ying-Shiung Lee
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ABSTRACT: Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV.
Based on changes in gene expression of peripheral blood, we identified 52 signature genes that accurately discriminated acute SARS patients from non-SARS controls. While a general suppression of gene expression predominated in SARS-infected blood, several genes including those involved in innate immunity, such as defensins and eosinophil-derived neurotoxin, were upregulated. Instead of employing clustering methods, we ranked the severity of recovering SARS patients by generalized associate plots (GAP) according to the expression profiles of 52 signature genes. Through this method, we discovered a smooth transition pattern of severity from normal controls to acute SARS patients. The rank of SARS severity was significantly correlated with the recovery period (in days) and with the clinical pulmonary infection score.
The use of the GAP approach has proved useful in analyzing the complexity and continuity of biological systems. The severity rank derived from the global expression profile of significantly regulated genes in patients may be useful for further elucidating the pathophysiology of their disease.
BMC Genomics 02/2005; 6:132. · 4.07 Impact Factor
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ABSTRACT: Salmonella enterica serovar Choleraesuis (S. Choleraesuis), a highly invasive serovar among non-typhoidal Salmonella, usually causes sepsis or extra-intestinal focal infections in humans. S. Choleraesuis infections have now become particularly difficult to treat because of the emergence of resistance to multiple antimicrobial agents. The 4.7 Mb genome sequence of a multidrug-resistant S. Choleraesuis strain SC-B67 was determined. Genome wide comparison of three sequenced Salmonella genomes revealed that more deletion events occurred in S. Choleraesuis SC-B67 and S.Typhi CT18 relative to S. Typhimurium LT2. S. Choleraesuis has 151 pseudogenes, which, among the three Salmonella genomes, include the highest percentage of pseudogenes arising from the genes involved in bacterial chemotaxis signal-transduction pathways. Mutations in these genes may increase smooth swimming of the bacteria, potentially allowing more effective interactions with and invasion of host cells to occur. A key regulatory gene of TetR/AcrR family, acrR, was inactivated through the introduction of an internal stop codon resulting in overexpression of AcrAB that appears to be associated with ciprofloxacin resistance. While lateral gene transfer providing basic functions to allow niche expansion in the host and environment is maintained during the evolution of different serovars of Salmonella, genes providing little overall selective benefit may be lost rapidly. Our findings suggest that the formation of pseudogenes may provide a simple evolutionary pathway that complements gene acquisition to enhance virulence and antimicrobial resistance in S. Choleraesuis.
Nucleic Acids Research 02/2005; 33(5):1690-8. · 8.03 Impact Factor
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ABSTRACT: Premature coronary artery disease is very rare and complication with thrombus formation in the left ventricle is rarer still. A 23-year-old man was admitted to hospital for recent acute myocardial infarction after being struck by a basketball eight days previously. Echocardiography identified two peduncle thrombi at the apex of the left ventricle, which were confirmed with computed tomography. The proximal left anterior descending coronary artery was totally occluded. Following two weeks of treatment with heparin and warfarin, the patient agreed to undergo a coronary artery bypass graft and thrombectomy. The ecchymosed tissue around the coronary artery implied that a trauma injury might have been the cause of the coronary artery disease in this case. This work reviews the pathophysiology and natural history of coronary artery disease in a case of very young myocardial infarction.
Japanese Heart Journal 12/2004; 45(6):1029-35. · 0.40 Impact Factor
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ABSTRACT: Electrophysiological characteristics of an accessory pathway (AP) with a long ventriculoatrial (VA) interval (arbitrarily defined as > or = 50 ms and absence of continuous electrical activity) and no retrograde decremental property are described in this study. Fifteen patients (group 1) were compared with 171 patients with normal VA conduction (group 2). Mean VA conduction time was 77 +/- 24 versus 34 +/- 12 ms in group 1 versus group 2, respectively. Group 1 patients were older (55 +/- 14 vs 40 +/- 14 years), the male to female ratio was higher (2.8 vs 1.6), and APs were more prevalent on the right (60%) but manifest APs were lower (20% vs 54%) compared to group 2 patients (P < 0.05 in all cases). QRS morphology during induced atrioventricular reciprocating tachycardia was identical in both groups but the tachycardia cycle length was longer in group 1 (373 +/- 29 vs 344 +/- 50 ms, P < 0.05). Retrograde AP block cycle length and effective refractory period were greater in group 1 (362 +/- 59 vs 293 +/- 57 ms; 330 +/- 58 vs 273 +/- 55 ms, both P < 0.05). Adenosine (up to 18 mg) and verapamil (5-10 mg) failed to block the VA conduction via AP during ventricular pacing. In group 1 the number of radiofrequency lesions for a successful ablation were significantly less (3 +/- 2 vs 6 +/- 5, P < 0.05). In conclusion, APs with a long VA interval and no decremental retrograde conduction have electrophysiological characteristics that are different from those with a short VA interval. Role of aging deserves further exploration.
Pacing and Clinical Electrophysiology 10/2004; 27(9):1250-6. · 1.35 Impact Factor
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ABSTRACT: Cardiac hamartomas are very rare and are demarcated masses of enlarged, hypertrophied, mature myocytes and collagen tissue. Cardiac hamartomas are generally circumscribed in the right ventricle or atrium, but not reported in the crista terminalis (CRT). The CRT is crucial in electrophysiology, is related to arrhythmogenesis, and is targeted by radiofrequency catheter procedures. Previous works only described the benign natures of prominent CRT using non-invasive methods. This study describes an unusual cardiac hamartoma originating from the CRT and extending toward the tricuspid valve. Microscopically, this hamartoma comprised dense collagen and adipose tissue, mixed with hypertrophy, but with disarrayed cardiomyocytes. An irregular gap junction, connexin43, was demonstrated in this cardiac hamartoma.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 05/2004; 444(4):383-6. · 2.49 Impact Factor
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ABSTRACT: Advances in molecular and computational biology have led to the development of powerful, high-throughput methods for analysis of differential gene expression, which are opening up new opportunities in genomic medicine. DNA microarray technology has been enthusiastically integrated into basic biomedical research and will eventually become a molecular monitoring tool for various clinical courses.
As a core research facility of Chang Gung University (CGU) and Chang Gung Memorial Hospital (CGMH), the Genomic Medicine Research Core Laboratory (GMRCL) welcomes investigators from every discipline to employ DNA microarray technology in the quest for knowledge of genomic medicine. The first tasks for GMRCL are to optimize the standard operating procedures (SOP) for each instrument and to assure the quality of every procedure.
During the first year after the establishment of the GMRCL at the CGMH, we tested and adopted procedures that were satisfactory for our purposes. These procedures included: replication of bacterial stocks, amplification of human DNA clones, annotation of each DNA clone, production of cDNA microarrays, validation of RNA quality and quantity, labeling of target specimens, competitive hybridization, scanning of slides, data analysis, and post-microarray validation of results. We present a summarization of the materials and procedures used at the GMRCL and discuss the reasons for using them.
The information about the cDNA microarray analysis system at the GMRCL is compliant with the minimal information about a microarray experiment (MIAME) format. The information may be useful to both the investigators who are using this core facility and researchers at other institutes, who will establish their own in-house cDNA microarray systems.
Chang Gung medical journal 05/2004; 27(4):243-60.
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ABSTRACT: The 3D structure of the atrioventricular conduction axis incorporating detailed cellular and molecular composition, especially that relating to gap-junctional proteins, is still unclear, impeding mechanistic understanding of cardiac rhythmic disorders.
A 3D model of the rabbit atrioventricular conduction axis was reconstructed by combining histological and immunofluorescence staining on serial sections. The exact cellular boundaries, especially those between transitional cells and atrial myocardium, were demarcated by a dense and irregular desmin-labeling pattern in conductive myocardium. The model demonstrates that the atrioventricular conduction axis is segregated into 2 connecting compartments, 1 predominantly expressing connexin45 (compact node and transitional cells) and the other predominantly coexpressing connexin43 and connexin45 (His bundle, lower nodal cells, and posterior nodal extension). The transitional zone shows unique features of spatial complexity, including a bridging bilayer structure (a deep transitional zone connecting with a superficial atrial-transitional overlay) and asymmetrical continuity (wider atrial-transitional interfaces and shorter atrial-axial distances in the hisian portion than in the ostial portion). In the latter compartment, the His bundle, lower nodal cells, and posterior nodal extension form a continual axis and longitudinal transitional-axial interface.
Key findings of the present study are the demonstration of a distinct anatomical border between transitional and atrial cells, connection between transitional cells and both lower nodal cells and posterior nodal extension, and distinctive connexin expression patterns in different compartments of the rabbit atrioventricular conduction axis. These features, synthesized in a novel 3D model, provide a structural framework for the interpretation of nodal function.
Circulation 04/2004; 109(9):1172-9. · 14.74 Impact Factor
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ABSTRACT: The effect of percutaneous transluminal angioplasty (PTA) in the treatment of hemodialysis vascular access stenosis is attenuated by a high restenosis rate, which results mainly from neointimal hyperplasia. Cellular proliferation is one of the most important biological mechanisms involved in neointimal hyperplasia and may be a potential target of intervention to prevent restenosis.
We investigated the activity of cellular proliferation of restenotic lesions by means of immunohistochemistry, using an antibody to the proliferating cell nuclear antigen. Specimens from 10 primary stenotic and 20 restenotic lesions of 30 Brescia-Cimino fistulae were obtained during revision.
The proliferation index of the restenotic group was strikingly significantly greater than that of the primary stenotic group (intima, P < 0.001; media, P = 0.001). Proliferation indices of patients with diabetes in the restenotic group were significantly higher than those of patients without diabetes (intima, P = 0.028; media, P = 0.002). In the restenotic group, proliferation indices correlated negatively with the interval from PTA to restenosis (intima, r = -0.741; P < 0.001; media, r = -0.589; P = 0.006) and positively with the number of PTAs per lesion (intima, r = 0.754; P < 0.001; media, r = 0.506; P = 0.004).
We show markedly high cellular proliferation activity in early restenotic lesions of arteriovenous fistulae. These findings indicate that adjunctive antiproliferative therapy is mandatory in preventing restenosis after PTA, especially in patients with diabetes.
American Journal of Kidney Diseases 02/2004; 43(1):74-84. · 5.43 Impact Factor
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ABSTRACT: Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and plays a key role in reverse cholesterol transport. The aim of the current study was to test the statistical association between two HL gene promoter polymorphisms (HL-514C/T and HL-250G/A) and lipoprotein profiles in a Taiwanese-Chinese population.
A sample population of 716 Taiwanese-Chinese individuals was analyzed. DNA was extracted from the blood and genotypes were determined by polymerase chain reaction, restriction enzyme digestion, and agarose gel electrophoresis.
Analysis of the data revealed that these two polymorphisms are in strong linkage disequilibrium (D/D(max)=0.97, P<0.001). A significantly lower total cholesterol/HDL-C ratio was noted for carriers with the -514T and -250A alleles compared to non-carriers (P=0.007 and 0.004, respectively). A significant trend of the association was also found on the high levels of high-density-lipoprotein cholesterol (HDL-C) among carriers with the -514T and -250A alleles as opposed to that of non-carriers (P=0.030 and 0.023, respectively). Multivariate analysis has demonstrated that the effects of HL-514C/T and HL-250G/A polymorphisms on HDL-C levels were not affected by subjects' sex, body mass index, plasma triglyceride levels and the cholesterol ester transfer protein gene TaqIB polymorphism. Subgroup analysis on each sex has revealed that the two studied polymorphisms were significantly associated with HDL-C levels among males but not significant in women. The same association between obese and non-obese men was not consistent. The P-value of the respective polymorphisms on HDL-C levels were 0.012 and 0.002 among obese men, but not significant among non-obese men.
Analysis of our data revealed an independent association between the HL gene promoter polymorphisms and HDL-C levels in Taiwanese-Chinese. The data also suggests that the HL-514C/T and HL-250G/A polymorphisms interact with sex and obesity on HDL-C levels. The findings give clues for identifying high risk population in preventive medicine and clinical diagnosis. The subsequent impacts on treatment profiles and prognosis were derived from this study.
Atherosclerosis 01/2004; 172(1):135-42. · 3.79 Impact Factor
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ABSTRACT: Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice. The understanding of the pathophysiology of AF has changed drastically during the last several decades. Recent observations have challenged the concept of the multiple circuit reentry model in favor of single focus or single circuit reentry models. Atrial electrical dysfunction provides a favorable substrate and transmembrane ionic currents are key determinants. Interest has also been generated in the role of angiotensin converting enzyme (ACE) inhibition in reversing the electrical and structural remodeling. Reverting to the sinus rhythm seems to be the best way for reverse remodeling of atria during atrial fibrillation. Antiarrhythmic drugs (AADs) are only modestly effective. Of these amiodarone seems to provide the most benefits. Drugs like verapamil and ACE inhibitors may also help as adjuvant therapies in the reverse remodeling of atria. Nonpharmacological methods have been used to control both rate and rhythm for patients with AF. Recently, there has been a surge in interest to focal ablation of atrial foci. Focal sources of AF are commonly found in pulmonary veins (PV). Ablation in pulmonary veins through identification of the earliest endocardial activation has met with variable success. Anatomical approaches have involved circumferential radiofrequency ablation of pulmonary vein ostia using novel techniques such as balloon based circumferential ultrasound ablation system and circular cryoablation catheter. Most recently the segmental approach is preferred because the myocardial fibers surrounding the PV are not continuous. Segments where musculature is present can be identified using high frequency depolarization signals recorded through multi-electrode loop catheter or even conventional catheters.
Chang Gung medical journal 11/2003; 26(10):712-21.
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ABSTRACT: This study was aimed to ascertain the effect of sleep deprivation on subsequent cerebral ischemia in the rat hippocampal formation. Seven days after transient global cerebral ischemia induced by four-vessel occlusion method, most of the pyramidal cells in the hippocampal CA1 subfield underwent disruption and pyknosis as detected by cresyl violet staining. With OX-42, OX-18, OX-6 and ED1 immunohistochemistry, robust microglia/macrophage reactions were observed in the CA1 and dentate hilus. The majority of reactive microglia was rod-shaped, bushy or amoeboidic cells bearing hypertrophic processes. Astrocytes also displayed hypertrophic processes, whose immunostaining for glial fibrillary acidic protein was markedly enhanced. The ischemia-induced neuronal damage and glial reactions, however, were noticeably attenuated in rats subjected to pretreatment with sleep deprivation for five consecutive days. The most drastic effect was the diminution of OX-18, OX-6 and ED1 immunoreactivities, suggesting that the immune potentiality and/or phagocytosis of these cells was suppressed by prolonged sleep deprivation prior to ischemic insult. It is postulated that sleep deprivation may have a preconditioning influence on subsequent lethal cerebral ischemia. Hence, sleep deprivation may be considered as a therapeutic strategy in brain ischemic damage.
Brain Research 10/2003; 984(1-2):170-81. · 2.73 Impact Factor
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ABSTRACT: Scavenger receptor class B type I (SR-BI) is a multiligand cell-surface receptor that mediates the selective uptake of lipid from HDL cholesterol (HDL-C) into cells. This study hypothesized an association between functional variants in the promoter region of SR-BI gene and HDL-C levels.
We identified 2 novel mutations in the SR-BI gene promoter region by using single-strand conformation polymorphism. One mutation was an 11-bp CCCCGCCCCGT deletion mutation from positions -140 to -150 relative to the transcription start site, corresponding to an Sp1 binding site; the other was a C-->T substitution at position -142. Twenty-six of 690 unrelated subjects were heterozygous for the -140 to -150 deletion mutation, and the allele frequency in this population was 0.02. This study showed that the deletion variant prevented binding of Sp1 to this region of the SR-BI promoter and effectively reduced transcriptional activities in HepG2 cells. Notably, the -140 to -150 deletion mutation was significantly associated with increased HDL-C levels and explained approximately 0.5% of the variation in HDL-C levels in this population.
A genetic variant at the SR-BI gene promoter region might explain a significant proportion of individual differences in HDL-C levels among Taiwanese Chinese. Our results require further replication in an independent population.
Arteriosclerosis Thrombosis and Vascular Biology 10/2003; 23(10):1869-74. · 6.37 Impact Factor
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ABSTRACT: This article describes the additional use of incremental atrial burst pacing (A1A1) and double atrial extrastimulation with a predefined fast pathway conducted A2 (A1A2A3), rather than single atrial extrastimulation (A1A2) only, to characterize typical atrioventricular nodal reentrant tachycardia (AVNRT). The authors noted an additional 32% of patients had multiple anterograde AV nodal physiology demonstrated when A1A1 or A1A2A3 protocols were deployed compared to more conventional A1A2 protocols. The A2H2max (449 +/- 147 vs 339 +/- 94 ms) and A3H3max (481 +/- 120 vs 389 +/- 85 ms) were higher in 31 patients where multiple jumps in the AV nodal conduction curve were obtained (group 1) compared to 192 patients where only single jump was obtained (group 2) (both P < 0.01). Postablation, the degree of reduction of A2H2max (49%) and A3H3max (50%) in group 1 was greater than in group 2 (38% and 42%, respectively, P < 0.05). In seven of group 1 patients in whom A1A2A3 stimulation was required to reveal multiple jumps, the A2H2max remained unchanged after ablation (237 +/- 89 vs 214 +/- 59, P > 0.05). A3H3max was the only parameter that shortened significantly after ablation. Generally, successful ablation resulted in loss of multiple discontinuities in A1A1/A1H1 or A2A3/A3H3 curves. In conclusion, a combination of A1A2, A1A1, and A1A2A3 are required to fully elucidate AVNRT. Significant shortening of AHmax or loss of multiple jumps after ablation indicates successful elimination of AVNRT in these patients.
Pacing and Clinical Electrophysiology 09/2003; 26(9):1849-55. · 1.35 Impact Factor
