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Biomedical subjects

D Wu

Publications and source records attributed to D Wu.

At least 127 records · Page 7Linked to original sources
PubMed2000

[Study on the effect of alcohol on embryonic development by using in vitro post-implantation rat whole embryo culture].

In order to explore the effects of drinking alcohol during pregnancy on embryonic development and its mechanisms, a post-implantation whole embryo culture(WEC) technique was used. The 9.5 day rat embryos were explanted in rat serum medium(immediately centrifugal serum, ICS) with alcohol(0.0.4.1.0, 2.00 and 4.00 g/L), and cultured for 48 hours. The index of embryo development and morphological scores induced by alcohol were observed. The result showed that alcohol had obviously effects on the development and growth of embryos with a dose-response relationship. Embryonic development of 0.4 g/L group was not significantly different from the control group, whereas 1.0 g/L group could interfere with the development score of mid-brain, forebrain, neurotube, and visceral yolk sac(VYS) circle obviously. All scores of the 2.00 g/L group were significantly lower than that of control group (P < 0.05). Moreover, the rate of embryo lethality and teratogenecity were obvious increased. It is concluded that alcohol has developmental toxicity and teratogenicity. The target organ affected by alcohol is brain. The effects of alcohol on the developmental differentiation of visceral yolk sac and DNA synthesis are probably related to its developmental abnormalities.

Animals↗
PubMed2000

Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription.

The Dishevelled (Dvl) gene family encodes cytoplasmic proteins that are necessary for Wnt signal transduction. Utilizing the yeast two-hybrid system, we identified protein phosphatase 2Calpha (PP2C) as a Dvl-PDZ domain-interacting protein. PP2C exists in a complex with Dvl, beta-catenin, and Axin, a negative regulator of Wnt signaling. In a Wnt-responsive LEF-1 reporter gene assay, expression of PP2C activates transcription and also elicits a synergistic response with beta-catenin and Wnt-1. In addition, PP2C expression relieves Axin-mediated repression of LEF-1-dependent transcription. PP2C utilizes Axin as a substrate both in vitro and in vivo and decreases its half-life. These results indicate that PP2C is a positive regulator of Wnt signal transduction and mediates its effects through the dephosphorylation of Axin.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Successful lysis of right and left heart thrombus by tissue plasminogen activator.

Tissue plasminogen activator (t-PA) was administered to three patients with newly developed intracardiac thrombi. Cases 1 and 2 developed right heart thrombi after radiofrequency ablation for atrioventricular nodal reentrant tachycardia and case 3 had tachycardia-related cardiomyopathy and a left ventricular thrombus. In all three patients, the intracardiac thrombi were successfully eliminated following t-PA therapy without major bleeding complications. These observations suggest that t-PA is effective in lysing new thrombus complicating radiofrequency ablation or heart failure and may be the therapy of choice in these conditions. Cathet. Cardiovasc. Intervent. 49:91-96, 2000.

Adult↗
PubMed2000

Effects of BIIB513 on ischemia-induced arrhythmias and myocardial infarction in anesthetized rats.

Na+/H+ exchange (NHE) plays an important role in the regulation of the intracellular pH (pHi) and in cardiac cell injury induced by ischemia and reperfusion. In the present study, we investigated the effects of BIIB513, a selective NHE-1 inhibitor on myocardial ischemia induced arrhythmias and myocardial infarction, provoked by 30 minutes of left main coronary artery occlusion followed by 2 hours of reperfusion in an anesthetized rat model. Intravenous administration of BIIB513 (0.01-3.0 mg/kg) did not induce changes in blood pressure or heart rate. BIIB513 (0.01, 0.1, 0.3, 1.0, 3.0 mg/kg) given prior to the coronary artery occlusion dose-dependently reduced ventricular premature beats, ventricular tachycardia, and a complete suppression of ventricular fibrillation down to the dose of 0.1 mg/kg. BIIB513 (0.01, 0.1, 0.3, 1.0, 3.0 mg/kg) given prior to the coronary artery occlusion dose-dependently reduced the infarct size with an ED50 value of 0.16 mg/kg. BIIB513 (1.0 mg/kg) given prior to reperfusion also reduced infarct size by 47.3 +/- 13.1%. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase (CPK). In conclusion, the present study demonstrates the cardioprotective ability of NHE-1 inhibition during myocardial ischemia and reperfusion by reducing serious ventricular arrhythmias and myocardial infarct size in anesthetized rats.

Animals↗
PubMed2000

Indocyanine green angiographic findings in diffuse choroidal hemangioma associated with Sturge-Weber syndrome.

PURPOSE: To analyze indocyanine green angiography (ICGA) features in one case of diffuse choroidal hemangioma associated with Sturge-Weber syndrome. METHODS: Color fundus photography, fluorescein angiography (FA) and ICGA were performed in a patient with diffuse choroidal hemangioma associated with Sturge-Weber syndrome. RESULTS: The diffuse choroidal hemangioma was not identified by FA. ICGA revealed that the vascular tissue of the diffuse hemangioma filled rapidly with dye during the arterial phase of the choroidal angiogram; copious dye leakage appeared early and persisted into the late phase of angiography. Late "wash-out" phenomenon was not observed 30 minutes after dye injection. Sectors of reduced choroidal perfusion in the upper or lower half of the midperiphery were present. CONCLUSION: ICGA may be an important and sensitive technique in detecting the diffuse choroidal hemangioma associated with Sturge-Weber syndrome.

Adolescent↗
PubMed2000

The effect of carotenoids on the expression of cell surface adhesion molecules and binding of monocytes to human aortic endothelial cells.

Several large epidemiological studies have shown a correlation between elevated plasma carotenoid levels and decreased risk of cardiovascular disease (CVD). One proposed mechanism for the beneficial effect of carotenoids is through functional modulation of potentially atherogenic processes associated with the vascular endothelium. To test this, we incubated confluent human aortic endothelial cell (HAEC) cultures (passages 4-8) for 24 h with each of the five most prevalent carotenoids in human plasma, which are alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and lycopene, at an approximate concentration of 1 micromol/l. Carotenoids were solubilized in 0.7% (v/v) tetrahydrofuran and incorporated into FBS before adding to cell culture medium. Due to disparate solubilities in aqueous medium, final concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and lycopene were 1.7, 1.1, 0.7, 0.9, and 0.3 micromol/l and monolayers accumulated 647, 158, 7, 113, and 9 pmol/mg protein, respectively. Monolayers were then stimulated with IL-1beta (5 ng/ml) for 6 h with subsequent determination of cell surface expression of adhesion molecules as measured by an enzyme-linked immunosorbent assay (ELISA). To assess endothelial cell adhesion to monocytes, IL-1beta-stimulated monolayers were incubated for 10 min with 51Cr-labeled U937 monocytic cells and adhesion determined by isotope counting. Pre-incubation of HAEC with beta-carotene, lutein and lycopene significantly reduced VCAM-1 expression by 29, 28, and 13%, respectively. Pre-incubation with beta-carotene and lutein significantly reduced E-selectin expression by 38 and 34%, respectively. Pre-treatment with beta-carotene, lutein and lycopene significantly reduced the expression of ICAM-1 by 11, 14, and 18%, respectively. While other carotenoids were ineffective, lycopene attenuated both IL-1beta-stimulated and spontaneous HAEC adhesion to U937 monocytic cells by 20 and 25%, respectively. Thus, among the carotenoids, lycopene appears to be most effective in reducing both HAEC adhesion to monocytes and expression of adhesion molecules on the cell surface.

Anticarcinogenic Agents↗
PubMed2000

Ethanol and arachidonic acid produce toxicity in hepatocytes from pyrazole-treated rats with high levels of CYP2E1.

Ethanol and polyunsaturated fatty acids such as arachidonic acid were shown to be toxic and cause apoptosis in HepG2 cells which express CYP2E1 but not in control HepG2 cell lines. The goal of the current study was to extend the observations made with the HepG2 cells to non-transformed, intact hepatocytes. Rats were treated with pyrazole to increase CYP2E1 levels, hepatocytes were isolated and placed into culture and treated for varying time points with ethanol or arachidonic acid. Comparisons were made to hepatocytes from saline-treated rats, with low CYP2E1 content. Incubation with ethanol (100 mM) or especially arachidonic acid (60 microM) resulted in loss of viability of hepatocytes from the pyrazole-treated rats, without any effect on the hepatocytes from the saline-treated rats. The toxicity appeared to be apoptotic in nature and was prevented by diallyldisulfide, an inhibitor of CYP2E1. Toxicity was reduced by trolox, an antioxidant. The treatment with ethanol or arachidonic acid resulted in release of cytochrome c into the cytosol fraction, and activation of caspase 3 (but not caspase 1) in hepatocytes from the pyrazole-treated rats but not hepatocytes from the saline-treated rats. The activation of caspase 3 was prevented by diallyldisulfide, by trolox, and by DEVD-fmk. The latter also prevented the toxicity produced by ethanol or arachidonic acid. These results extend previous observations found with HepG2 cells expressing CYP2E1 to intact hepatocytes and suggest that release of cytochrome c and activation of caspase 3 play a role in the overall pathway by which CYP2E1 contributes towards the hepatotoxic actions of ethanol and polyunsaturated fatty acids.

Animals↗
PubMed2000

The multifocal electroretinogram in age-related maculopathies.

To measure and compare the multifocal electroretinogram in control group and patients with age-related maculopathies, 17 eyes of control subjects, 9 eyes of wet-form ARMD, 8 eyes of dry-form ARMD and 14 eyes of idiopathic macular hole were tested with VERIS Sciences 4.0. The latencies and average response densities of 6 ring retinal regions in control eyes were compared with those in ARMD and macular hole. The amplitude depression and latency prolongation were found in age-related maculopathies. The changes of multifocal ERG were dramatic in wet-form ARMD and moderate in dry-form ARMD and IMH, which were correspondent with the pathological changes of the diseases. Our results suggest that the multifocal electroretinogram can be used to quantity the visual function in age-related maculopathies.

Aged↗
PubMed2000

Expression of porcine endogenous retrovirus in peripheral blood leukocytes from ten different breeds.

The expression of porcine endogenous retroviruses (PERV) was investigated in primary porcine peripheral blood leukocytes (PBL) of ten different pig breeds. The data suggest that PERV exists in all porcine PBL. A new retroviral element, a foamy-like pol-related sequence, was also detected in PBL. Three types of PERV were detected in almost every animal. The breeding of PERV-free pigs is likely to be difficult. Further studies are required to assess the infectious disease risks associated with xenotransplantation.

Animals↗
PubMed2000

Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway.

The DEP domain of Dishevelled (Dvl) proteins transduces signals to effector proteins downstream of Dvl in the Wnt pathway. Here we report that DEP-containing mutants inhibit Wnt-induced, but not Dvl-induced, activation of the transcription factor Lef-1. This inhibitory effect is weakened by a K434M mutation. Nuclear magnetic resonance spectroscopy revealed that the DEP domain of mouse Dvl1 comprises a three-helix bundle, a beta-hairpin 'arm' and two short beta-strands at the C-terminal region. Lys 434 is located at the tip of the beta-hairpin 'arm'. Based on our findings, we conclude that DEP interacts with regulators upstream of Dvl via a strong electric dipole on the molecule's surface created by Lys 434, Asp 445 and Asp 448; the electric dipole and the putative membrane binding site are at two different locations.

3T3 Cells↗
PubMed2000

Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist.

Calcitonin gene-related peptide (CGRP) is one of the most potent endogenous vasodilators known. This peptide is increased during migraine attacks and has been implicated in the pathogenesis of migraine headache. Here we report on the first small molecule selective CGRP antagonist: BIBN4096BS. In vitro, this compound is extremely potent at primate CGRP receptors exhibiting an affinity (Ki) for human CGRP receptors of 14.4 +/- 6.3 (n = 4) pM. In an in vivo model, BIBN4096BS in doses between 1 and 30 micrograms kg-1 (i.v.) inhibited the effects of CGRP, released by stimulation of the trigeminal ganglion, on facial blood flow in marmoset monkeys. It is concluded that BIBN4096BS is a potent and selective CGRP antagonist.

Animals↗
PubMed2000

Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus.

Compared with young mice, old mice infected with influenza virus have significantly higher pulmonary viral titres, although these can be reduced significantly with dietary vitamin E supplementation. T helper 1 (Th1) cytokines, especially interferon-gamma (IFN-gamma), play an important role in defending against influenza infection. However, there is an age-associated loss of Th1 cytokine production. Prostaglandin E2 (PGE2) production, which increases with age, can modulate the T helper cell function by suppressing Th1 cytokine production. To investigate the mechanism of vitamin E supplementation on reduction of influenza severity in old mice, we studied the cytokine production by splenocytes, and PGE2 production by macrophages (Mphi), in young and old C57BL mice fed semipurified diets containing 30 (control) or 500 parts per million (ppm) (supplemented) vitamin E for 8 weeks, and then infected with influenza A/PC/1/73 (H3N2). Old mice fed the control diet had significantly higher viral titres than young mice; old mice fed the vitamin E-supplemented diet had significantly lower pulmonary viral titres than those fed the control diet (P = 0.02 and 0.001 for overall age and diet effect, respectively). Following influenza infection, interleukin (IL)-2 and IFN-gamma production was significantly lower in old mice than in young mice. Vitamin E supplementation increased production of IL-2 and IFN-gamma in old mice; higher IFN-gamma production was associated with lower pulmonary viral titre. Old mice fed the control diet showed significantly higher lipopolysaccharide (LPS)-stimulated Mphi PGE2 production than old mice fed the vitamin E diet or young mice fed either diet. There was no significant age difference in IL-6, IL-1beta, or tumour necrosis factor-alpha (TNF-alpha) production by splenocytes. Young mice fed the vitamin E-supplemented diet had significantly lower IL-1beta (day 7) and TNF-alpha production (day 5) compared with those fed the control diet. Old mice fed the vitamin E-supplemented diet had significantly lower TNF-alpha production (day 2) than those fed the control diet. Our results indicate that the vitamin E-induced decrease in influenza viral titre is mediated through enhancement of Th1 cytokines, which may be the result of reduced PGE2 production caused by vitamin E.

Aging↗
PubMed2000

Massive localized lymphedema: additional locations and association with hypothyroidism.

We report the second series of a new entity called "massive localized lymphedema in morbidly obese patients" (MLL), recently described in medical literature. Our 6 cases present additional locations as well as an association with hypothyroidism. Huge masses, of longstanding duration ranging from 9 months to 8 years, afflicted the thigh, popliteal fossa, scrotum, suprapubic and inguinal region, and abdomen of morbidly obese adults. Although clinical impressions were generally of a benign process, including lipoma and recurrent cellulitis, the possibility of a malignant neoplasm could not be eliminated. Poorly defined and non-encapsulated, these skin and subcutaneous lesions were most remarkable for their sheer size, measuring 50.6 cm in mean diameter (range, 38-75 cm) and weighing a mean of 6764.5 g (range, 2,060-12,000 g) The overlying skin exhibited the induration and peau d'orange characteristic of chronic lymphedema. Grossly and histologically, a prominent marbled appearance, rendered by fibrous bands intersecting lobules of adipose tissue, simulated sclerosing well differentiated liposarcoma. However, the absence of atypical stromal cells, atypical adipocytes, and lipoblasts precluded the diagnosis of well differentiated liposarcoma. Instead, reactive features, encompassing lymphatic vascular ectasia, mononuclear cell infiltrates, fibrosis, and edema between the collagen fibers, as well as ischemic changes including infarction and fat necrosis, established the diagnosis of MLL. Although the pathogenesis of MLL may be as simple as obstruction of efferent lymphatic flow by a massive abdominal pannus and/or prior surgery, the presence of hypothyroidism in 2 of our patients suggests an alternative pathogenesis. Recognition of this entity by both clinicians and pathologists should avert a misdiagnosis as a low-grade liposarcoma.

Adipose Tissue↗
PubMed2000

Effect of long-term dietary antioxidant supplementation on influenza virus infection.

This study compared the effect of vitamin E on the course of influenza infection with that of other antioxidants. (In a previous study we showed that short-term vitamin E supplementation significantly decreased pulmonary viral titer in influenza-infected old mice). Eighteen-month-old C57BL/6NCrlBR mice were fed one of the following semisynthetic diets for 6 months: control, vitamin E supplemented, glutathione supplemented, vitamin E and glutathione supplemented, melatonin supplemented, or strawberry extract supplemented. After influenza virus challenge, mice fed vitamin E-supplemented diet had significantly lower pulmonary viral titers compared to those fed the control diet (10(2.6) vs 10(4.0), p < .05) and were able to maintain their body weight after infection (1.8+/-0.9 g weight loss/5 days postinfection in vitamin E group vs 6.8+/-1.4 g weight loss/5 days postinfection in control group, p < .05). Other antioxidants did not have a significant effect on viral titer or weight loss. There was a significant inverse correlation of weight loss with food intake (r = -.96, p < .01), indicating that the observed weight changes were mainly due to decreased food intake. Pulmonary interleukin (IL)-6, IL-1beta, and tumor necrosis factor (TNF)-alpha levels increased significantly postinfection. The vitamin E group had lower lung IL-6 and TNF-alpha levels following infection compared to the control group. In addition, there was a significant positive correlation between weight loss and lung IL-6 (r = .77, p < .01) and TNF-alpha (r = .68, p < .01) levels. Because IL-6 and TNF-alpha have been shown to contribute to the anorexic effect of infectious agents, the prevention of weight loss by vitamin E might be due to its reduced production of IL-6 and TNF-alpha following infection. Thus, among the antioxidants tested, only vitamin E was effective in reducing pulmonary viral titers and preventing an influenza-mediated decrease in food intake and weight loss. Other dietary antioxidant supplementations that reduced one or more measures of oxidative stress (4-hydroxynonenal, malondialdehyde, and hydrogen peroxide) did not have an effect on viral titer, which suggests that, in addition to its antioxidant activity, other mechanisms might be involved in vitamin E's beneficial effect on lowering viral titer and preventing weight loss.

Aldehydes↗
PubMed2000

Metabolic gene polymorphisms and risk of dysmenorrhea.

We conducted a molecular epidemiologic study in rural China to investigate the association of the cytochrome P450 2D6 (CYP2D6) and glutathione S-transferase Mu (GSTM1) polymorphisms with dysmenorrhea. This report includes 435 subjects, 129 with and 306 without any history of dysmenorrhea, who did not smoke or drink alcohol. We obtained information on dysmenorrhea and major covariates by questionnaire interview. We used categorical methods and logistic regression models to evaluate the individual and combined associations of CYP2D6 and GSTM1 polymorphisms with dysmenorrhea and its subgroups, occasional (N = 70) and recurrent (N = 59), with adjustment for age, education, occupation, passive smoke exposure, age of menarche, parity, contraceptive method, height, and body mass index. Both variant CYP2D6 and GSTM1 genotypes were associated with increased risk of recurrent dysmenorrhea [for CYP2D6, odds ratio (OR) = 1.7 and 95% confidence interval (95% CI) = 0.9-3.1; for GSTM1, OR = 1.8 and 95% CI = 1.0-3.4). There was no appreciable association between these variant genotypes and occasional dysmenorrhea. When both the CYP2D6 and GSTM1 genotypes were considered together, the highest risk of recurrent dysmenorrhea was found among women with variant genotypes in both CYP2D6 and GSTM1 (OR = 3.1; 95% CI = 1.2-8.0). This study provides evidence of genetic susceptibility to recurrent dysmenorrhea.

Adult↗
PubMed2000

A peripheral site of action for the attenuation of baroflex-mediated bradycardia by intravenous mu-opioid agonists.

We previously reported that i.v. DAMGO (Tyr-D-Ala-Gly-NMePhe-Gly-ol), a selective mu-opioid agonist, causes an increase in blood pressure with no change in heart rate in unanesthetized sheep and subsequently demonstrated that DAMGO attenuates baroreflex-mediated bradycardia. To determine the site and mechanism by which mu-agonists inhibit baroreflex sensitivity, we have carried out further investigations by using DAMGO and another mu-agonist, DALDA (Tyr-D-Arg-Phe-Lys-NH2). The bradycardic response to norepinephrine (NE) was significantly blunted after i.v. DAMGO or DALDA in both nonpregnant and pregnant sheep. In contrast, the tachycardic response to sodium nitroprusside (SNP) remained unchanged in the presence of DAMGO or DALDA. In view of the highly restricted distribution of DALDA across the blood-brain barrier (BBB), we hypothesized that the blunting of reflex-mediated bradycardia by mu-opioid agonists can occur peripherally. Pretreatment with the quaternary opioid antagonist, naloxone methiodide (NM), completely blocked the attenuation of baroreflex sensitivity by DAMGO and DALDA in both nonpregnant and pregnant animals. These data suggest that in addition to central mechanisms, mu-opioid agonists can inhibit baroreflex sensitivity at a peripheral site, most likely by inhibiting vagal influence on heart-rate control rather than by acting directly at baroreceptors.

Animals↗
PubMed2000

Crystallization and preliminary analysis of neurolysin.

Neuropeptidases inactivate or modify the activity of peptide neurotransmitters and neurohormones. The neuropeptidase neurolysin acts only on short peptides and accepts a variety of cleavage-site sequences. Structures of the enzyme and enzyme-substrate complexes will help to determine the mechanisms of substrate selectivity used by this enzyme. Crystals of recombinant neurolysin have been grown in the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 157.8, b = 88.0, c = 58.4 A. Data have been collected to 2.3 A at 110 K with observed diffraction to 1.8 A. Circular dichroism measurements suggest that the enzyme is primarily alpha-helical, with little beta-strand secondary structure. Sequence-based secondary-structure prediction supports this conclusion.

Animals↗