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Biomedical subjects

K K Wu

Publications and source records attributed to K K Wu.

At least 19 recordsLinked to original sources
PubMed2006

Stimulation of embryo hatching and implantation by prostacyclin and peroxisome proliferator-activated receptor delta activation: implication in IVF.

BACKGROUND: Successful IVF depends in part on quality embryos. Recent work suggests that prostaglandin I(2) (PGI(2) or prostacyclin) promotes the development of embryos in vitro and enhances their implantation potential. The mechanism underlying the effects of PGI(2) is unclear. It has been reported that peroxisome proliferator-activated receptor delta (PPARdelta) mediates the effects of PGI(2) at the implantation sites. METHODS: The expression of PPARdelta in the preimplantation embryos was examined by RT-PCR, western blot analysis and immunohistochemistry. Synthetic PPARdelta ligand (L-165041) and PPARdelta targeted (PPARdelta(-/-)) embryos were used to reveal the roles of PPARdelta in PGI(2)-stimulated and spontaneous embryo development. RESULTS: Preimplantation embryos express PPARdelta, which is essential for the enhancing effect of PGI(2) and the spontaneous progression of preimplantation embryos. Enhanced blastocyst hatching by PGI(2) (P < 0.05) was abrogated by PPARdelta deletion. Blastocyst formation and embryo hatching were impaired in PPARdelta(-/-) embryos. PPARdelta deletion significantly reduced embryo cell proliferation (P < 0.01); PPARdelta activation increased embryo cell proliferation (P < 0.05). PPARdelta activation enhanced the implantation of wild-type (WT) embryos (P < 0.05); PPARdelta deletion reduced embryo implantation (P < 0.05). CONCLUSIONS: PPARdelta is essential for spontaneous and PGI(2)-stimulated embryo development and blastocyst hatching. The implantation of cultured embryos is enhanced by PPARdelta activation. PPARdelta represents a novel therapeutic target to improve IVF outcome.

Acetates↗
PubMed2006

Attention-Deficit/Hyperactivity Disorder and working memory: a task switching paradigm.

This study investigated working memory (WM) in children with Attention-Deficit/Hyperactivity Disorder (ADHD) using a task switching paradigm with Stroop color-word stimuli which required participants to switch from color-naming to word-reading. High and low WM load conditions were compared by manipulation of task reminders as a tempo cue. The sample comprised 83 children with ADHD and 29 normal children comparable in age (aged 7 to 13). Within the ADHD group, participants were divided according to the presence or absence of Learning Disability (LD). Results indicated that children with ADHD had slower response times and less accurate responses in general, however, the ADHD groups were not consistently slower in the high WM load condition. Instead, an impairment in adjusting response speed to cope with higher task demands (i.e., high WM load condition) was found. These results do not support the previously documented association between ADHD and a primary deficit in WM for task switching. However, children with ADHD do demonstrate a specific difficulty in slowing down for a demanding task. Present findings suggest that earlier proposals of under-arousal and poor state regulation in ADHD deserve renewed attention.

Analysis of Variance↗
PubMed2005

Control of cyclooxygenase-2 transcriptional activation by pro-inflammatory mediators.

Cyclooxygenase-2 (COX-2) plays a key role in diverse inflammatory conditions. Its cellular levels depend on transcriptional activation by pro-inflammatory mediators. The mechanism by which phorbol esters and cytokines activate COX-2 gene expression has been extensively characterized. Several endogenous molecules and natural products have been reported to inhibit COX-2 expression by targeting at the transcriptional activation induced by pro-inflammatory mediators. This review highlights the importance of C/EBP beta and NF-kappa B in COX-2 transcriptional activation by proinflammatory mediators and as targets of inhibition by endogenous molecules such as melatonin and natural products including salicylate and polyphenols.

Animals↗
PubMed2004

Smoking cessation among Hong Kong Chinese smokers attending hospital as outpatients: impact of doctors' advice, successful quitting and intention to quit.

To identify factors affecting current smokers' intention to quit smoking and factors associated with successful quitting among ex-smokers in Hong Kong. A cross-sectional survey of Chinese patients attending medical and surgical Specialist Outpatient Clinics (SOPCs) of public hospitals in Hong Kong, using a structured questionnaire. Results of the 642 respondents, 21% were current smokers, 9% were ex-smokers and 69% were non-smokers. 74% of the smokers reportedly received quitting advice from doctors. Among the current smokers, past quitting attempts, receiving information from sources other than doctors, believing that doctor's advice was useful, believing that all smokers should quit smoking and a positive attitude towards quitting were associated with intention to quit. Among those who had attempted to quit, being older (aged 50 or above), being retired/unemployed and consuming more than 10 cigarettes per day were associated with successful quitting. We found that advice from doctors on quitting smoking did not have any impact on Chinese smokers quitting or future intention to quit and reflect the inadequacy of advice given by Hong Kong doctors. The predictors of intention to quit and successful quitting identified in the study could be used to design future smoking cessation services.

Adult↗
PubMed2003

The development of the Chinese version of Impact of Event Scale--Revised (CIES-R).

BACKGROUND: This is an exploratory study on the psychometric properties and normative data of the Chinese translation of the Impact of Event Scale - Revised (CIES-R). METHODS: The original Impact of Event Scale - Revised was translated into Chinese and the comparability of content was verified through back-translation procedures. The study consisted of a sample of 116 patients from the Accident and Emergency Department. RESULTS: The reliability of the Chinese version was verified. The validity of the Chinese version as a measure of psychological distress was supported by the positive correlations between the various subscale scores of CIES-R (i. e., Intrusion, Avoidance, and Hyperarousal) and General Health Questionnaire-20. However, the independence of the three subscales was not supported. CONCLUSIONS: The present result suggests that normative information for different age groups and clinical samples might be different. Further study with clinical sample and investigation of the relationship between CIES-R and other diagnostic measures of PTSD are discussed.

Adolescent↗
PubMed2003

Prospective study of the A455V polymorphism in the thrombomodulin gene, plasma thrombomodulin, and incidence of venous thromboembolism: the LITE Study.

Plasma thrombomodulin (soluble TM; sTM) is considered to be a marker of endothelial injury, but a recent report indicated that the relationship of sTM with thrombosis is complex. Venous thromboembolic events were identified in adults in two longitudinal cohort studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, totaling 21 690 participants. After 8 years of follow-up, sTM was measured in baseline plasma of 305 participants who developed venous thrombosis and 607 who did not. Thrombomodulin A455V genotype was determined in 302 cases and 626 controls. There was no difference in the prevalence of the three TM genotypes between cases and controls and no difference in age-adjusted mean values of sTM by genotype. There were no associations of age-adjusted sTM or TMA455V genotype with overall venous thromboembolism or with thrombosis in any subtype of venous thromboembolism.

Age Factors↗
PubMed2003

Aspirin and salicylate inhibit colon cancer medium- and VEGF-induced endothelial tube formation: correlation with suppression of cyclooxygenase-2 expression.

To determine whether aspirin and salicylate suppress colon cancer cell-mediated angiogenesis, we evaluated the effects of aspirin and sodium salicylate on endothelial tube formation on Matrigel. Aspirin and sodium salicylate concentration-dependently inhibited human endothelial cell (EC) tube formation induced by conditioned medium collected from DLD-1, HT-29 or HCT-116 colon cancer cells. Aspirin and sodium salicylate at pharmacological concentrations were equally effective in blocking tube formation. Neutralizing antivascular endothelial growth factor (VEGF) antibodies blocked colon cancer medium-induced tube formation. VEGF receptor 2 but not receptor 1 antibodies inhibited tube formation to a similar extent as anti-VEGF antibodies. These results indicate that VEGF interaction with VEGF receptor 2 is the primary mechanism underlying colon cancer-induced angiogenesis. Aspirin or sodium salicylate inhibited VEGF-induced tube formation in a concentration-dependent manner comparable to that of inhibition of colon cancer medium-induced endothelial tube formation. It has been shown that cyclooxygenase-2 (COX-2) is pivotal in cancer angiogenesis. We found that colon cancer medium-induced COX-2 protein expression in EC and aspirin or sodium salicylate suppressed the cancer-induced COX-2 protein levels at concentrations correlated with those that suppressed endothelial tube formation. Furthermore, aspirin and sodium salicylate inhibited COX-2 expression stimulated by VEGF. These findings indicate that aspirin and other salicylate drugs at pharmacological concentrations inhibit colon cancer-induced angiogenesis which is correlated with COX-2 suppression.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Prostacyclin enhances embryo hatching but not sperm motility.

BACKGROUND: Recently we discovered that the human oviduct synthesizes abundant prostacyclin (PGI(2)). Gene knock-out studies suggest that PGI(2) is essential to endometrial decidualization, but the effects of PGI(2) on sperm and embryos have not been reported. METHODS: The effects of PGI(2) on human sperm were analysed by a computer-assisted semen analysis system. The effects of PGI(2) on mouse embryos were examined based on the rates of complete hatching. The expression of PGI(2) receptor (IP) was evaluated by Western blot analysis and immunohistochemistry. The binding of PGI(2) to embryos was confirmed by radioligand binding assay. Finally, cAMP levels were assessed in PGI(2)-challenged embryos. RESULTS: Iloprost (a stable PGI(2) analogue) did not affect the motility or the overnight survivability of human sperm. Western blot analysis did not detect IP in the sperm plasma membrane. In contrast, the hatching of mouse embryos was enhanced by iloprost (ED(50) 6.7 nmol/l). Exposure to iloprost during 8-cell to morulae or morulae to early blastocyst stages was critical to enhanced hatching. This coincided with the developmental stage-specific expression of IP. Although iloprost bound to blastocysts, it did not significantly increase cAMP. CONCLUSION: PGI(2) enhanced the hatching of mouse embryos but not the motility of human sperm.

Animals↗
PubMed2002

Plasma agouti-related protein level: a possible correlation with fasted and fed states in humans and rats.

We measured plasma concentrations of agouti-related protein (AGRP) in humans and rats and determined whether these were affected by ingestion of a meal after fasting. In 17 healthy human subjects, the mean plasma concentration of AGRP was lower in the fed state than in the fasted state. Two hours after a breakfast meal, AGRP levels dropped by 39%. By contrast, a continued fast for 2 h increased the average AGRP concentration by 73%. In rats with diet-induced obesity, refeeding resulted in a 50% decrease in plasma AGRP concentrations following a fasting-refeeding protocol. Our results support the notion that plasma AGRP may serve as a biomarker for the transition from a fasted to the satiated state.

Adult↗
PubMed2002

Characterization of the human prostaglandin H synthase 1 gene (PTGS1): exclusion by genetic linkage analysis as a second modifier gene in familial thrombosis.

Genetic evidence from a large Vermont kindred indicates that an unknown gene promotes thrombosis when inherited in conjunction with type I protein C deficiency. Cyclooxygenase-1 [prostaglandin H synthase 1 gene (PTGS1)] was tested as a plausible candidate for the unknown gene because of its role in primary hemostasis. The complete sequence of PTGS1 (25 638 nucleotides) was determined from a 37 kb human genomic cosmid clone to characterize intronic regions and subsequently to allow the search for mutations by direct sequencing of genomic DNA. Northern blot analysis confirms usage of a newly described distal poly-adenylation signal. Short tandem repeat (STR) sequences found in intron 2 and the 3' flanking region were developed as new genetic markers for PTGS1. The position of PTGS1 was refined on the CHLC chromosome 9 linkage map using the new markers scored in four Centre d'Etude du Polymorphisme Humain families and multipoint linkage analysis. Direct sequencing of DNA from members of the Vermont kindred led to the discovery of two new single nucleotide polymorphisms (SNPs) that give rise to non-conservative amino acid changes in the signal peptide (Arg(8) to Trp and Pro(17) to Leu) of cyclooxygenase-1. Linkage analysis of the SNP and STR markers indicated that PTGS1 is not the interacting gene associated with an increased incidence of thrombosis in the Vermont kindred.

Base Sequence↗
PubMed2001

Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice.

BACKGROUND: Increasing evidence supports the role of heme oxygenase-1 (HO-1) in cytoprotective response and iron homeostasis. The object of this study was to investigate whether adenovirus-mediated gene transfer of HO-1 in arteries reduces iron overload and inhibits lesion formation in apolipoprotein E (apoE)-deficient mice. METHODS AND RESULTS: Infection of rat aortic smooth muscle cells with adenovirus carrying the human HO-1 gene (Adv-HO-1) resulted in a high-level expression of HO-1 protein, which effectively reduced the hemin-induced iron overload in these cells. Adenovirus-mediated gene transfer in arteries in vivo was achieved by direct injection of Adv-HO-1 into the left ventricles of anesthetized animals. Transgene was expressed in the endothelium and aortic lesion of apoE-deficient mice after they had received recombinant adenovirus for 1 week and gradually decayed during the next 5 weeks. When young apoE-deficient mice (14 weeks old) received Adv-HO-1 (2.5 x 10(9) pfu) for 6 weeks, lesions that developed in the aortic root or aortic arch were significantly smaller than those in control littermates receiving empty viral vector. Furthermore, the iron deposition as well as tissue iron content was much less in aortic tissue of Adv-HO-1-treated mice. The inhibitory effect of HO-1 gene transfer on the progression of advanced lesions was also observed in older apoE-deficient mice (20 weeks old) receiving Adv-HO-1 intraventricularly. CONCLUSIONS: Overexpression of HO-1 in vascular cells facilitates iron metabolism and attenuates development of atherosclerosis in apoE-deficient mice.

Adenoviridae↗
PubMed2001

Colocalization and interaction of cyclooxygenase-2 with caveolin-1 in human fibroblasts.

Results from our previous study suggest that cyclooxygenase-2 (COX-2) induced by phorbol 12-myristate 13-acetate (PMA) may be localized to caveolae-like structures (Liou, J.-Y., Shyue, S.-K., Tsai, M.-J., Chung, C.-L., Chu, K.-Y., and Wu, K. K. (2000) J. Biol. Chem. 275, 15314-15320). In this study, we determined subcellular localization of COX-2 and caveolin-1 by confocal microscopy. COX-2 in human foreskin fibroblasts stimulated by PMA (100 nm) or interleukin-1beta (1 ng/ml) for 6 h was localized to plasma membrane in addition to endoplasmic reticulum and nuclear envelope. Caveolin-1 was localized to plasma membrane, and image overlay showed colocalization of COX-2 with caveolin-1. This was confirmed by the presence of COX-2 and caveolin-1 in the detergent-insoluble membrane fraction of cells stimulated by PMA. Immunoprecipitation showed complex formation of COX-2 with caveolin-1 in a time-dependent manner. A larger quantity of COX-2 was complexed with caveolin-1 in PMA-treated than in interleukin-1beta-treated cells. Purified COX-2 complexed with glutathione S-transferase-fused caveolin-1, which was not inhibited by the scaffolding domain peptide. Caveolin-1-bound COX-2 was catalytically active, and its activity was not inhibited by the scaffolding domain peptide. These results suggest that COX-2 induced by PMA and interleukin-1beta is colocalized with caveolin-1 in the segregated caveolae compartment. Because caveolae are rich in signaling molecules, this COX-2 compartment may play an important role in diverse pathophysiological processes.

Blotting, Western↗
PubMed2001

State of complementary and alternative medicine in cardiovascular, lung, and blood research: executive summary of a workshop.

The National Heart, Lung, and Blood Institute and the National Center for Complementary and Alternative Medicine recently cosponsored a workshop on the use of complementary and alternative medicine (CAM) in cardiovascular, lung, and blood research. In view of the increasing use of CAM by the general public, it is imperative to promote credible research by the established biomedical community. The goal of this workshop was to enhance the exchange of information and ideas between alternative medicine practitioners and scientists in cardiovascular, lung, and blood research and to foster collaborative research among these researchers. The workshop focused on 5 areas of research, including a historical and cultural perspective of CAM, methodological issues in clinical trials, herbal medicine, chelation therapy, mind/body (meditation) therapy, and acupuncture. CAM has become widely used without rigorously proven efficacy and safety. To protect the public, it was recommended that the fundamental mechanistic research for these CAM approaches be vigorously pursued and that any large-scale clinical trial be carefully executed to avoid any waste of resources and any unnecessary risk. It was felt that standardization of botanical products and procedure-based CAM intervention, such as acupuncture and meditation, is essential for meaningful basic and clinical research. Although botanical products properly consumed are perceived as generally safe, potential herb-drug interactions are a major safety concern. Clearly, many challenges need to be addressed by the scientific community before the public can be assured of the proper use of CAM.

Acupuncture↗
PubMed2001

Selective augmentation of prostacyclin production by combined prostacyclin synthase and cyclooxygenase-1 gene transfer.

BACKGROUND: We tested the hypothesis that combined cyclooxygenase-1 (COX-1) and prostacyclin synthase (PGIS) gene transfer selectively augments prostacyclin production without a concurrent overproduction of other prostanoids. METHODS AND RESULTS: ECV304 cells were transfected with bicistronic pCOX-1/PGIS versus pCOX-1 or pPGIS, and prostanoids were analyzed. Contrary to the high prostaglandin E2 synthesis in pCOX-1 transfected cells, selective prostacyclin formation was noted with bicistronic plasmid transfection. Next, we determined the optimal ratio of Ad-COX-1 to Ad-PGIS by transfecting human umbilical vein endothelial cells with various titers of these 2 adenoviral constructs and determined the level of protein expression and prostanoid synthesis. Our results show that optimal ratios of adenoviral titers to achieve a large prostacyclin augmentation without overproduction of prostaglandin E2 or F2alpha were 50 to 100 plaque forming units (pfu) of Ad-COX-1 to 50 pfu of Ad-PGIS per cell. A higher Ad-PGIS to Ad-COX-1 ratio caused a paradoxical decline in prostacyclin synthesis. CONCLUSIONS: Prostacyclin synthesis can be selectively augmented by cotransfecting endothelial cells with an optimal ratio of COX-1 to PGIS. Combined COX-1 and PGIS gene transfer has the potential for therapeutic augmentation of prostacyclin.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Selective suppression of CCAAT/enhancer-binding protein beta binding and cyclooxygenase-2 promoter activity by sodium salicylate in quiescent human fibroblasts.

The anti-inflammatory actions of salicylates cannot be explained by inhibition of cyclooxygenase (COX) activity. This study demonstrates that sodium salicylate at a therapeutic concentration suppressed COX-2 gene transcription induced by phorbol 12-myristate 13-acetate and interleukin 1beta by inhibiting the binding of CCAAT/enhancer-binding protein beta to its promoter region of COX-2. By contrast, salicylate did not inhibit nuclear factor kappaB-dependent COX-2 induction by tumor necrosis factor alpha. The inhibitory effect of sodium salicylate was restricted to serum-deprived quiescent cells. These findings indicate that contrary to the current view that salicylate acts via inhibition of nuclear factor kappaB the pharmacological actions of aspirin and salicylates are mediated by inhibiting CCAAT/enhancer-binding protein beta binding and transactivation. These findings have a major impact on the conceptual understanding of the mechanism of action of salicylates and on new drug discovery and design.

Alkaline Phosphatase↗
PubMed2001

Thrombomodulin Ala455Val polymorphism and risk of coronary heart disease.

BACKGROUND: Thrombomodulin (TM) is expressed on the endothelial surface and plays an important role in vasoprotection. A common polymorphism of TM at amino acid position 455 with an alanine (A) to valine (V) transition was previously reported to be associated cross-sectionally with acute myocardial infarction. Whether this single nucleotide polymorphism predicts risk of developing coronary heart disease (CHD) is unclear. METHODS AND RESULTS: Within a large cohort study, we identified 467 incident CHD cases during an average of 5 years of follow-up. We determined TM-455 genotypes on 376 CHD cases (23% black, 77% white) and a reference sample of 461. The AA genotype was significantly more prevalent in noncases than in cases (P:=0.016). The prevalences of the AA genotype in noncase blacks and whites were 93% and 67%, respectively. The AA genotype frequency was significantly reduced in black cases versus noncases (P:=0.018). It was also lower in white cases than in noncases, but the difference was not statistically significant (P:=0.066). Weighted proportional hazards regression analysis after adjustment for age, sex, and other CHD risk factors showed that having the V allele increased risk of CHD by 6.1-fold (risk ratio 6.1, 95% CI 1.7 to 22.9) in blacks but did not significantly increase the risk in whites. CONCLUSIONS: The TM A455V polymorphism predicts risk of developing CHD in blacks.

Adult↗
PubMed2001

Up-regulation of endothelial nitric-oxide synthase promoter by the phosphatidylinositol 3-kinase gamma /Janus kinase 2/MEK-1-dependent pathway.

Our recent study indicates that lysophosphatidylcholine (LPC) enhances Sp1 binding and Sp1-dependent endothelial nitric oxide synthase (eNOS) promoter activity via the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 (MEK-1) signaling pathway (Cieslik, K., Lee, C.-M., Tang, J.-L., and Wu, K. K. (1999) J. Biol. Chem. 274, 34669-34675). To identify upstream signaling molecules, we transfected human endothelial cells with dominant negative and active mutants of Ras and evaluated their effects on eNOS promoter activity. Neither mutant altered the basal or LPC-induced eNOS promoter function. By contrast, a dominant negative mutant of phosphatidylinositol 3-kinase gamma (PI-3Kgamma) blocked the promoter activity induced by LPC. Wortmannin and LY 294002 had a similar effect. AG-490, a selective inhibitor of Janus kinase 2 (Jak2), also reduced the LPC-induced Sp1 binding and eNOS promoter activity to the basal level. LPC induced Jak2 phosphorylation, which was abolished by LY 294002 and the dominant negative mutant of PI-3Kgamma. LY 294002 and AG-490 abrogated MEK-1 phosphorylation induced by LPC but had no effect on Raf-1. These results indicate that PI-3Kgamma and Jak2 are essential for LPC-induced eNOS promoter activity. This signaling pathway was sensitive to pertussis toxin, suggesting the involvement of a G(i) protein in PI-3Kgamma activation. These results indicate that LPC enhances Sp1-dependent eNOS promoter activity by a pertussis toxin-sensitive, Ras-independent novel pathway, PI-3Kgamma/Jak2/MEK-1/ERK1/2.

Antibodies↗