Biomedical subjects

D Y Li

Publications and source records attributed to D Y Li.

At least 19 recordsLinked to original sources

PubMed2005

On the correlation between surface roughness and work function in copper.

Both surface roughness (SR) and work function (WF) are important characteristics of a solid surface. Understanding the relationship between SR and WF is necessary in order to apply the Kelvin probe technique to characterize surface behavior. In this study, SR and WF of copper surfaces were measured using atomic force microscopy and scanning Kelvin probe, respectively. Experimental results showed that WF decreased with increase of SR. Using sine functions, a capacitor model was proposed and a correlation between WF and SR was established. The theoretical predictions of WF were in good agreement with experimental results. The model is also useful for analyzing the effect of tip geometry on measurements of WF.

Journal Article↗

PubMed2004

Aspirin inhibits ox-LDL-mediated LOX-1 expression and metalloproteinase-1 in human coronary endothelial cells.

BACKGROUND: Aspirin is thought to exert salutary effects in vascular disease states by inhibiting platelet aggregation. Endothelial activation, accumulation of oxidized low-density lipoprotein (ox-LDL) and intense inflammation also characterize atherosclerotic plaque in acute myocardial ischemia. Ox-LDL induces expression of lectin-like receptors (LOX-1) on endothelial cells and leads to the expression of matrix metalloproteinases (MMPs), which destabilize the atherosclerotic plaque. We hypothesized that aspirin may interfere with LOX-1 expression and subsequent MMP activation. METHODS AND RESULTS: Cultured human coronary artery endothelial cells (HCAECs) were incubated with aspirin (1-5 mM), sodium salicylate (5 mM) or the cyclo-oxygenase inhibitor indomethacin (0.25 mM) before treatment with ox-LDL. Aspirin, in a dose- and time-dependent fashion, reduced ox-LDL-mediated LOX-1 expression (P<0.01). Ox-LDL also increased MMP-1 expression and activity, and treatment of HCAECs with aspirin decreased this effect (P<0.01). Ox-LDL also enhanced the activity of p38MAPK in HCAECs, and aspirin blocked this effect of ox-LDL (P<0.01). Treatment of HCAECs with salicylate, but not indomethacin, resulted in a suppression of LOX-1 expression, an effect similar to that of aspirin. Importantly, both aspirin and salicylate, but not indomethacin, decreased superoxide anion generation in ox-LDL-treated HCAECs (P<0.05). CONCLUSION: These observations suggest that aspirin inhibits ox-LDL-mediated LOX-1 expression and interferes with the effects of ox-LDL in intracellular signaling (p38MAPK activation) and subsequent MMP-1 activity. These novel effects of aspirin may complement its platelet inhibitory effect in acute myocardial ischemia.

Anions↗

PubMed2004

Peripheral blood mononuclear cell DNA 6-thioguanine metabolite levels correlate with decreased interferon-gamma production in patients with Crohn's disease on AZA therapy.

6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are well known for their lymphocytotoxic and bone marrow suppressive effects in the management of patients with leukemia. Although their immunosuppressive properties are mediated by the active AZA antimetabolite 6-thioguanine (6-TG), its mechanism of action is largely unknown. In IBD, a significant inverse correlation has been shown between erythrocyte 6-TG metabolite levels and disease activity, further supporting the proposed immunosuppressive role for 6-TG. Since leukocytes possess quantitatively different purine metabolic pathways compared to erythrocytes, this study aims to measure lymphocyte DNA 6-TG metabolites and correlate levels with the INF-gamma and IL-10 cytokine profile in patients with Crohn's disease (CD). Forty-six adult patients with CD, either naive (17) or on long-term (>4-month) AZA therapy (29), had erythrocyte and lymphocyte DNA 6-TG levels measured by reverse-phase HPLC under UV detection (6-TG, 340 nm). Lymphocyte DNA 6-TG was expressed as picomoles per milligram of DNA. Lymphocyte DNA 6-TG metabolite levels were correlated with INF-gamma and IL-10 cytokine profiles using the OptEIA kit (Pharmigen). Lymphocyte DNA 6-TG metabolite levels correlate with erythrocyte 6-TG levels (P < 0.03) but not total patient leukocyte levels. Erythrocyte 6-TG metabolite levels correlated (P < 0.01) inversely with INF-gamma but not IL-10 cytokine levels. This study suggests a preferential dampening of the TH1 response on exposure to 6-TG and a possible immunosuppressive mechanism of action for AZA. Future studies are needed to determine if cytokine profiles can be used to predict recalcitrant CD to AZA therapy.

Azathioprine↗

PubMed2002

Protection of myocytes from hypoxia-reoxygenation injury by nitric oxide is mediated by modulation of transforming growth factor-beta1.

BACKGROUND: Reoxygenation injury is a result of several complex events, including release of reactive oxygen species, protein kinase C (PKC) activation, and altered expression of transforming growth factor-beta1 (TGF-beta(1)). Nitric oxide (NO) generally protects tissues from reperfusion injury. METHODS AND RESULTS: We examined the modulation of TGF-beta1 expression and activity and PKC activation in cultured rat heart myocytes exposed to a brief period of hypoxia-reoxygenation (H-R) by NO donor 3-morpholino-sydnonimine (SIN-1). H-R resulted in an increased expression of total TGF-beta1 (mRNA and protein) but a decrease in the release of active TGF-beta1. Myocyte PKC-alpha protein level was not altered by H-R, but its phosphorylation was augmented. Pretreatment of myocytes with SIN-1 diminished myocyte injury quantified as lactate dehydrogenase release. Simultaneously, release of active TGF-beta1 increased and total TGF-beta1 expression decreased (all P<0.05 versus H-R alone). PKC-alpha phosphorylation increased further in cells treated with SIN-1. The effects of SIN-1 were blocked by the NO scavenger phenyl-tetramethyl-imidazoline-oxyl-oxide as well as by the PKC inhibitor staurosporine. To examine if another NO donor would have a similar effect, cardiomyocytes were treated with nitroglycerin before H-R. With nitroglycerin treatment, similar to SIN-1 treatment, myocyte injury was diminished, TGF-beta1 release increased, and total TGF-beta1 expression decreased. CONCLUSIONS: These observations suggest modulation of TGF-beta1 expression as a novel mechanism of salutary effect of NO donors. PKC-alpha activation may play an important role in the protective effect of NO against H-R injury.

Animals↗

PubMed2002

Physical mapping of the 5S and 45S rDNA in teosintes.

The physical locations of the 5S and 45S rDNA sequences were examined in three types of teosinte, Zea mays ssp. mexicana (2n = 20), Zea diploperennis (2n = 20) and Zea perennis (2n = 40) by biotinylated fluorescence in situ hybridization (FISH). The tested materials only showed one hybridization site of 5S rDNA on their genomes, but they were different in the position of the signals. The hybridization site of Zea mays ssp. mexicana was located on the long arm of chromosome 2, indicating that it is the same as the cultivated maize in the position of 5S rDNA, while the sites of Zea diploperennis and Zea perennis were on the short arms of other chromosomes. For 45S rDNA, one hybridization site was detected at secondary constriction region of the satellite chromosomes in Zea mays ssp. mexicana and Zea diploperennis, while in Zea perennis, besides the site located at the secondary constriction region, a second site on the short arm of another chromosome pair was observed. Our results provide additional evidence for Zea mays ssp. mexicana being a subspecies of Zea mays.

DNA Probes↗

PubMed2002

Angiotensin II and IV stimulate expression and release of plasminogen activator inhibitor-1 in cultured human coronary artery endothelial cells.

There is increasing evidence that angiotensin II influences thrombogenesis by regulating the expression of plasminogen activator inhibitor-1 (PAI-1). In this study, the effects of angiotensin II and its receptors on the expression and release of PAI-1 and tissue-type plasminogen activator (t-PA) were examined in human coronary artery endothelial cells (HCAECs). As control, cells were treated with angiotensin IV. HCAECs incubated with angiotensin II increased the expression of PAI-1 mRNA in a concentration (10-9-10-5 M)- and time (6-24 h)-dependent manner. PAI-1 protein release was also increased in the culture medium of HCAECs treated with angiotensin II. The effects of angiotensin II (10-6 M) were blocked completely by the AT1 receptor blocker losartan (10-6 M) but not by the AT2 receptor blocker PD123319 (10-6 M). Angiotensin II pretreatment also slightly, but significantly, increased t-PA mRNA expression. This effect of angiotensin II on t-PA mRNA was blocked by losartan but not by PD123319. HCAECS treated with angiotensin II revealed large amounts of the lipid peroxidation product, malonaldehyde (MDA). The effects of angiotensin II on PAI-1 expression and MDA release were blocked by pretreatment of cells with alpha-tocopherol (10-5 M). In control experiments, treatment of HCAECs with angiotensin IV markedly increased PAI-1 mRNA expression and protein release. This effect of angiotensin IV was blocked by the AT4 receptor blocker divalinal (10-6 M). These observations indicate that AT1 receptor activation plays an important role in the stimulation of PAI-1 expression and release in response to angiotensin II. Upregulation of t-PA gene may reflect autoregulation in response to PAI-1 release. Angiotensin II-mediated activation of oxidation pathways may relate to uupregulation of PAI-1. This study also confirms that angiotensin IV upregulates PAI-1 expression in HCAECs.

Angiotensin II↗

PubMed2002

Oxidized low-density lipoprotein receptor LOX-1 and apoptosis in human atherosclerotic lesions.

BACKGROUND: Lectin-like oxidized LDL receptor-1 (LOX-1), a novel receptor for oxidized low-density lipoprotein, mediates oxidized low-density lipoprotein-induced apoptosis of endothelial cells, monocyte adhesion to endothelium, and phagocytosis of aged cells. The present study examined the role of LOX-1 and apoptosis in human atherosclerotic lesions. METHODS AND RESULTS: Grafted vein (n = 8), human carotid artery endarterectomy (n = 11), and normal human internal mammary artery (n = 8) specimens were used to study the expression of LOX-1 and apoptosis. LOX-1 expression was determined by reverse transcriptase-polymerase chain reaction, Western analysis, and immunostaining. Presence of apoptosis was determined by fluorescent in situ nick end-labeling staining and by the presence of poly (ADP-ribose) polymerase protein (an apoptotic marker). Expression of LOX-1 was significantly increased in atherosclerotic grafted vein and carotid artery specimens compared with that in normal arteries. LOX-1 was expressed in endothelial cells, macrophages, and smooth muscle cells. LOX-1 was extensively expressed in the new blood vessels in the core of advanced atherosclerotic lesions. Double immunostaining showed LOX-1 expression to be colocalized with apoptotic cells. Fluorescent in situ nick end-labeling staining showed that the apoptotic cells were present mostly in the rupture-prone regions of the atherosclerotic plaque. CONCLUSION: These observations indicate that LOX-1 is extensively expressed in the proliferated intima of grafted veins and in advanced atherosclerotic carotid arteries. Further, LOX-1 is colocalized with apoptotic cells. These observations may relate to the phenomenon of plaque rupture, and provide targets for developing new therapies.

Aged↗

PubMed2002

Anti-thrombotic effects of atorvastatin--an effect unrelated to lipid lowering.

Statins (3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been shown to reduce clinical events in excess of what can be explained by altering lipid profile. Statins have been shown to possess modest antioxidant and antiplatelet aggregatory effect. We postulated that statins may accordingly inhibit arterial thrombus formation. To assess the antithrombotic effects of atorvastatin, a commonly used statin, in response to an oxidant stimulus, we fed Sprague-Dawley rats either regular chow, or chow mixed with atorvastatin (1.25 mg/kg) for 10 days (n = 16 in each group). Eight rats in each group were also given oxidized low-density lipoprotein intravenously prior to the induction of thrombus. An occlusive thrombus was created in the abdominal aorta by application of Whatman paper soaked in 35% FeCl3. The time to occlusive thrombus formation was not altered by administration of oxidized low-density lipoprotein in the rats fed regular chow or chow mixed with atorvastatin. However, time to thrombosis was increased in the group given chow mixed with atorvastatin (26 +/- 4 minutes vs. 20 +/- 5 minutes, P < 0.02). To determine the mechanism of atorvastatin's antithrombotic effect, we measured the expression of endothelial constitutive nitric oxide synthase (cNOS) in rat aortas by Western analysis. The cNOS protein expression was enhanced 75% in rats fed chow with atorvastatin (P < 0.01 vs. rats fed regular chow). Plasma levels of total cholesterol and low-density lipoprotein-cholesterol were similar in all groups. This study shows that atorvastatin delays thrombus formation in arterial channels exposed to oxidant stress. This effect of atorvastatin appears to be related to increased expression of cNOS, which is known to inhibit platelet aggregation and induce vasodilatation. The effects of atorvastatin are independent of its effects on plasma cholesterol levels.

Animals↗

PubMed2001

Inhibition of LOX-1 by statins may relate to upregulation of eNOS.

LOX-1, a receptor for oxidized low-density lipoprotein (ox-LDL), plays a critical role in endothelial dysfunction and atherosclerosis; both of these conditions are associated with diminished expression of constitutive endothelial nitric oxide synthase (eNOS). Recent studies show that HMG CoA reductase inhibitors (statins) exert cardioprotective effect. We examined the role of LOX-1 in eNOS expression and modulation of this relationship by two different statins, simvastatin and atorvastatin in human coronary artery endothelial cells (HCAECs). Ox-LDL (40 microg/ml) upregulated the expression of LOX-1; simultaneously, there was a reduction in eNOS expression. Pretreatment of HCAECs with simvastatin or atorvastatin (1 and 10 microM) reduced ox-LDL-induced upregulation of LOX-1 and downregulation of eNOS (both P < 0.05). High concentration of statins (10 microM) was more potent than the low concentration (1 microM) (P < 0.05). Both statins also attenuated ox-LDL-mediated activation of MAP kinase. These observations indicate that statins attenuate the effect of ox-LDL on eNOS expression. Inhibitory effect on LOX-1 and subsequently MAP kinase activity provides a potential mechanism of beneficial effects of statins beyond lowering cholesterol.

Atorvastatin↗

PubMed2001

Attenuation of tissue P-selectin and MCP-1 expression and intimal proliferation by AT(1) receptor blockade in hyperlipidemic rabbits.

Angiotensin-II (Ang-II) participates in the development and progression of atherosclerosis by activating type 1 (AT(1)) receptors. In vitro studies show that inflammatory factors, such as P-selectin and MCP-1, which can be upregulated by Ang-II, play an important role in atherogenesis. We examined the effect of AT(1) receptor blockade with losartan on the expression of P-selectin and MCP-1 in hypercholesterolemic rabbits. Since AT(1) receptor blockade is associated with feedback upregulation of renin-angiotensin system (RAS), we also examined alterations in plasma Ang-II levels by losartan therapy. Male NZW rabbits were fed regular chow (high cholesterol diet or high cholesterol diet + losartan 25 mg/kg/day). As expected, there was a marked intimal proliferation in association with increase in serum cholesterol (P < 0.001). In addition, there was a modest increase in plasma Ang-II levels (P < 0.05), and a significant increase in the expression of AT(1) receptors, P-selectin and MCP-1 in aortas of high cholesterol diet rabbits. Concurrent administration of losartan with high cholesterol diet attenuated aortic intimal proliferation induced a fivefold increase in plasma Ang-II levels and caused a marked decrease in expression of P-selectin and MCP-1 without change in serum lipid levels and aortic AT(1) receptor expression. These observations in hypercholesterolemic animal models show that AT(1) receptor blockade is associated with modulation of P-selectin and MCP-1 expression concurrent with reduction in intimal proliferation. The rise in plasma Ang-II does not appear to limit the potential beneficial effect of losartan.

Angiotensin II↗

PubMed2001

Statins inhibit oxidized-LDL-mediated LOX-1 expression, uptake of oxidized-LDL and reduction in PKB phosphorylation.

OBJECTIVES: LOX-1, a lectin-like receptor on endothelial cells, facilitates the uptake of oxidized-LDL. Expression of LOX-1 is involved in the pathobiological effects of oxidized-LDL in endothelial cells, including apoptosis, suppression of cNOS activity and cell adhesion. Recent studies show that intracellular signal protein kinase B (PKB) is involved in the regulation of cNOS. Further, HMG CoA reductase inhibitors (statins) may affect LOX-1 expression. In this study, we examined the modulation of LOX-1 expression and PKB activity in response to oxidized-LDL by two different statins (simvastatin and atorvastatin). METHODS AND RESULTS: Cultured human coronary artery endothelial cells (HCAECs) were used in this study. Oxidized-LDL (40 microg/ml) was found to upregulate the expression of LOX-1 (mRNA and protein), enhance [125I]-ox-LDL uptake and to reduce the phosphorylation of PKB (p-PKB). Two different statins, simvastatin and atorvastatin (each 1 and 10 microM), upregulated the activity of PKB and decreased LOX-1 expression and [125I]-ox-LDL uptake. A high concentration of statins (10 microM) gave a more potent effect than the low concentration (1 microM). The effects of the two different statins were similar. CONCLUSIONS: These observations show that statins decrease LOX-1 expression, a novel oxidized-LDL endothelial receptor, and uptake of oxidized-LDL in HCAECs. The effect of statins on LOX-1 expression is associated with an increase in PKB activity in HCAECs.

Analysis of Variance↗

PubMed2001

Annonaceous acetogenins of the seeds from Annona muricata.

Muricatenol (1) is a new C37 non-THF ring acetogenin with four hydroxyls and one isolated double bond in the long aliphatic chain. 2,4-cis-Gigantetrocinone (2) and 2,4-trans-gigantetrocinone (3) have been isolated as their acetates by preparative TLC. 2,4-trans-Isoannonacin-10-one (4) and 2,4-trans-isoannonacin (5) have been isolated as only 2,4-trans-form for the first time (no cis-form). Also four known acetogenins, gigantetrocin-A (6), gigantetrocin-B (7), annomontacin (8), gigantetronenin (9) and a mixture of N-fatty acyl tryptamines have been isolated (10). Their structures have been established on the basis of spectral analyses. The CHCl3 fraction of the seeds showed strong antitumor activities.

Annonaceae↗

PubMed2001

Segmentation of medical ultrasonic image using hybrid neural network.

Objective. To solve one of the most difficult problems in multi-dimensional reconstruction of medical ultrasonic images: image segmentation. Method. A new segmental method based on hybrid neural network was presented in this paper. The hybrid neural network comprised two phases. The first phase was Kohonens self-organization neural network, which was used to segment and label the image coarsely. The feature vectors of those pixels within a specified distance from the cluster centers were employed to train the second phase--a three-layer perception network using back-propagation (BP) technique. Then the trained BP network was used to label every pixel of the image. In the end, a post-processing stage was used to remove the small isolated points and smooth out the contours of the segmented image. Result. The segmented image had smooth continuous edges, few noises or speckles, and the contour of ventricle was clear and accurate. Conclusion. Our method could segment the ultrasonic images accurately and effectively, and had a lot of advantages compared to traditional methods. The unsupervised segmentation problems could be solved using supervised methods.

Cardiovascular Physiological Phenomena↗

PubMed2001

PCR Based Cloning and Sequence Analysis of the Pichia pastoris Cystathionine beta-Synthase Gene.

The cystathionine beta-Synthase (CBS) gene of Pichia pastoris has been cloned by homology to the CBS gene of Saccharomyces cerevisiae. First, based on the homology alignment of CBS genes from different sources, a pair of degenerate PCR primers were designed to amplify a conservative fragment of Pichia pastoris CBS gene. After the sequence was revealed, 5' RACE and 3' RACE were performed separately. The whole sequence of Pichia pasotris CBS gene was assembled. This gene encodes a polypeptide of 501 residues. Comparison of deduced amino acid sequence of this new gene with that of S. cerevisiae CBS showed 54% identity. Disruption of CBS gene resulted in a Cys(-) auxotrophy in Pichia pastoris. Thesequence was submitted to GenBank/EMBL/DDBJ under Accession No.AF367364.

Journal Article↗

PubMed2001

[Studies on the chemical constituents of the seeds from Artabostrys hexapetalus (Annonaceae)].

AIM: To study the chemical constituents of the seeds from Artabotrys hexapetalus (L.f.) Bhandari (Annonaceae). METHODS: Various chromatographic techniques were used to separate and purify the constituents. Their structures were elucidated on the physico-chemical properties and spectral data. RESULTS: Eight compounds were isolated from the seeds of A. hexapetalus. They were identified as four neolignans: isoamericanin A (1), isoamericanol A (2), americanin B (3) and artabotrycinol (4), a semiterpenoid: (R)-artabotriol (5) and others: palmitic acid (6), beta-sitosterol (7) and daucosterol (8). CONCLUSION: Artabotrycinol (4) and (R)-artabotriol (5) are new compounds. Three other neolignans were isolated from this plant for the first time.

Annonaceae↗

PubMed2001

[Determination of annonaceous acetogenins in annonaceae plants by HPLC].

AIM: To develop a method for analysis of antitumor annonaceous acetogenins in Annonaceae plants by HPLC. METHODS: Squamostatin-B (1), squamocin (2) and annonin-VI (3) were used as standard substances. Chromatography column was a Rp-18; the mobile phase was methanol-water (90:10); the flow rate was 1.0 mL.min-1 and the detecting wavelength was 220 nm. RESULTS: A linear range was obtained from 2.3 to 13.8 micrograms with a good correlation. The recoveries of (1), (2) and (3) were 100.3%, 100.3% and 100.0%, respectively. CONCLUSION: This method was developed for the analysis of acetogenins by HPLC for the first time. The method is rapid, accurate and suitable for the analysis of the antitumor acetogenins in Annonaceae plants.

4-Butyrolactone↗

PubMed2000

Arteriovenous malformations in mice lacking activin receptor-like kinase-1.

The mature circulatory system is comprised of two parallel, yet distinct, vascular networks that carry blood to and from the heart. Studies have suggested that endothelial tubes are specified as arteries and veins at the earliest stages of angiogenesis, before the onset of circulation. To understand the molecular basis for arterial-venous identity, we have focused our studies on a human vascular dysplasia, hereditary haemorrhagic telangiectasia (HHT), wherein arterial and venous beds fail to remain distinct. Genetic studies have demonstrated that HHT can be caused by loss-of-function mutations in the gene encoding activin receptor-like kinase-1 (ACVRL1; ref. 5). ACVRL1 encodes a type I receptor for the TGF-beta superfamily of growth factors. At the earliest stage of vascular development, mice lacking Acvrl1 develop large shunts between arteries and veins, downregulate arterial Efnb2 and fail to confine intravascular haematopoiesis to arteries. These mice die by mid-gestation with severe arteriovenous malformations resulting from fusion of major arteries and veins. The early loss of anatomical, molecular and functional distinctions between arteries and veins indicates that Acvrl1 is required for developing distinct arterial and venous vascular beds.

Activin Receptors↗

PubMed2000

Effect of stable fish oil on arterial thrombogenesis, platelet aggregation, and superoxide dismutase activity.

We examined the influence of dietary stable fish oil on aortic thrombosis, platelet aggregation, and superoxide dismutase (SOD) activity in a rat model. Twenty-nine Sprague-Dawley rats were fed regular chow supplemented with stable fish oil preparation (for 1 or 3 weeks), and 37 rats fed regular chow served as controls. The abdominal cavity was opened, and the abdominal aorta isolated. Whatman paper impregnated with 35% FeCl3 was wrapped around the surface of the aorta, and aortic flow was continuously recorded. In control rats, an occlusive platelet-fibrin-rich thrombus was formed in 21 +/- 3 min. Dietary fish oil in a time-dependent fashion delayed time to thrombus formation (24 +/- 2 min in rats fed fish oil for 1 week and 31 +/- 2 min in rats fed fish oil for 3 weeks), inhibited platelet aggregation (21 +/- 5% vs. 45 +/- 6%; p < 0.01) and increased SOD activity (p < 0.01). We conclude that dietary supplementation with stable fish oil delays formation of arterial thrombus, probably by reducing platelet aggregation and oxidative stress-associated arterial injury.

Animals↗