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Biomedical subjects

X Liu

Publications and source records attributed to X Liu.

At least 163 records · Page 9Linked to original sources
PubMed2002

Potentiation of human lung fibroblast chemotaxis by the thromboxane A(2) analog U-46619.

Fibroblast production of extracellular matrix is crucial not only for normal tissue development and maintenance of tissue structure but also for the repair and remodeling processes after injury. Thromboxane A(2) (TXA(2)) is a potent mediator in inflammatory processes. The aim of this study was to investigate the effect of TXA(2) on chemotaxis of human fetal lung (HFL-1) fibroblasts induced by human plasma fibronectin or platelet-derived growth factor BB (PDGF-BB). By using the blindwell chamber technique, the TXA(2) agonist U-46619 alone had no chemotactic activity. However, U-46619 (200 nmol/L) stimulated HFL-1 fibroblast chemotaxis to human plasma fibronectin (20 microg/mL; 161.8% +/- 13.4%; P <.005) and to PDGF-BB (10 ng/mL; 188.5% +/- 7.0%; P <.005). Checkerboard analysis of human plasma fibronectin-directed migration confirmed that the TXA(2) agonist increased both chemotaxis and chemokinesis. The stimulatory effect of the TXA(2) agonist was concentration dependent and increased with time. Another agent known for stimulating the protein kinase C pathway, phorbol 12-myristate 13-acetate (10(-8) mol/L), had a similar effect, stimulating chemotaxis to fibronectin (146.2% +/- 8.6%). The stimulatory effect of the TXA(2) agonist on HFL-1 fibroblast chemotaxis was inhibited by the synthetic thromboxane receptor antagonist SQ29,548 (10(-5) mol/L) and the protein kinase C inhibitor calphostin (10(-7) mol/L). In summary, TXA(2) appears to stimulate fibroblast chemotaxis to fibronectin and PDGF, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of wound healing and the development of fibrotic disorders.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2002

Developmental expression of skeletal muscle heparan sulfate proteoglycans in turkeys with different growth rates.

Heparan sulfate proteoglycans (HSPG) are a group of extracellular matrix molecules that link skeletal muscle cells to their extrinsic environment. To investigate if HSPG expression is affected by muscle growth and gender, a turkey line (F) selected for increased 16-wk BW and its unselected random-bred control line, RBC2, were used in the present study. Heparan sulfate (HS) and HSPG levels were measured in embryonic and posthatch pectoralis major muscle. HS levels plateaued at embryonic day (ED) 16 in both lines. A significant decrease of HS occurred at ED 18 in F males and females, and at ED 20 and 22 in the RBC2 males and females, respectively. Embryonic HSPG levels peaked at ED 18, and were significantly higher from ED 14 through 18 in F males and females compared with those of the RBC2 line. Male pectoralis major muscle had more HSPG at early embryonic stages than female muscle in both lines. During 1 to 16 wk posthatch, F male and female pectoralis major muscle contained more HSPG than the RBC2 samples, and HSPG levels in F males were higher than those of the females. Myogenic satellite cells derived from F and RBC2 male and female pectoralis major muscle were cultured to measure HSPG expression during proliferation and differentiation. No significant difference in HSPG level was found between the RBC2 and F line cells. However, in both lines, male-derived satellite cells had more HSPG than the female cells during proliferation and differentiation. These data show that HS and HSPG expression are affected by muscle growth properties and sex.

Age Factors↗
PubMed2002

Comparison of alteration of cell surface carbohydrates of the chinchilla tubotympanum and colonial opacity phenotype of Streptococcus pneumoniae during experimental pneumococcal otitis media with or without an antecedent influenza A virus infection.

Experimental and clinical studies suggest that influenza A virus promotes Streptococcus pneumoniae-induced otitis media; however, the mechanism underlying this synergistic interaction has not been completely defined. In this study, glycoconjugate expression patterns were evaluated on the cell surface in the chinchilla eustachian tube (ET) lumen of a cohort challenged intranasally (i.n.) with S. pneumoniae type 6A, which is predominantly transparent and a cohort with an antecedent influenza A virus infection, followed by i.n. inoculation with S. pneumoniae. The labeling patterns obtained with six lectin probes revealed that the binding of Bandeiraea simplicifolia lectin II, succinylated wheat germ agglutinin, and peanut agglutinin were significantly increased in the lumenal surface of the ET in the cohort infected with both pathogens compared to the cohort inoculated with only S. pneumoniae, which indicated that N-acetylglucosamine (GlcNAc) and D-galactose residues were exposed. A significant decreased labeling with Sambucus nigra agglutinin in the combined influenza A virus and pneumococcus infection cohort suggested that there were few sialic acid residues remaining in the ET epithelium. In addition, the colonial opacity of S. pneumoniae during the disease course was examined. The opaque phenotype was predominant among the pneumococcus isolates from the middle-ear fluid in the cohort infected with the both pathogens. Together, these data suggest that the synergic effect of influenza A virus and S. pneumoniae on the changes of the carbohydrate moieties in the ET epithelium and that the selection of the opaque variant may facilitate the pneumococcal invasion of the middle ear.

Acetylglucosamine↗
PubMed2002

Do mental disorders matter? A study of absenteeism among care seeking Gulf War veterans with ill defined conditions and musculoskeletal disorders.

AIMS: To investigate the extent that common psychological conditions contribute to lost work among individuals with musculoskeletal and ill defined conditions. METHODS: Cross sectional health and work related survey evaluating Gulf War veterans seeking Department of Defense health care for Gulf War related health concerns. Ordered probit models were used to study whether a provider diagnosed musculoskeletal condition (ICD-9 codes 710-739) or "signs, symptoms, and ill defined conditions" (ICD-9 codes 780-799) have an effect on recent lost work over the previous 90 days in the presence of one or more psychological conditions (ICD-9 codes 290-320) after controlling for sociodemographic variables. RESULTS: Bivariate analyses revealed that musculoskeletal conditions, ill defined conditions, and psychological conditions were positively associated with lost work. Multivariate analyses showed an independent effect of both psychological conditions and musculoskeletal conditions. A significant interaction existed between psychological conditions and musculoskeletal conditions: the presence of a coexisting psychological condition considerably increased the likelihood that a musculoskeletal disorder resulted in lost work, or vice versa. CONCLUSIONS: Psychological conditions appear to be an important contributor to absenteeism among individuals with musculoskeletal and ill defined conditions. A limitation of the cross sectional design was the inability to sequence the onset of conditions.

Absenteeism↗
PubMed2002

A statistically valid alternative to the TDT.

OBJECTIVE: To present an alternative linkage test to the transmission/disequilibrium test (TDT) which is conservative under the null hypothesis and generally more powerful under alternatives. METHODS: The exact distribution of the TDT is examined under both the null hypothesis and relevant alternatives. The TDT is rewritten in an alternate form based on the contributions from each of the three relevant parental mating types. This makes it possible to show that a particular term in the estimate is an exact tie and thus to rewrite the estimate without this term and to replace the multinomial 'variance estimate' of Spielman et al. [Am J Hum Genet 1993;52:506-516] by the binomial variance. RESULTS: The resulting test is shown to be a stratified McNemar test (SMN). The significance level attained by the SMN is shown to be conservative when compared to the asymptotic chi(2) distribution, while the TDT often exceeds the nominal level alpha. Under alternatives, the proposed test is shown to be typically more powerful than the TDT. CONCLUSION: The properties of the TDT as a statistical test have never been fully investigated. The proposed test replaces the heuristically motivated TDT by a formally derived test, which is also computationally simple.

Data Interpretation, Statistical↗
PubMed2002

Adverse pulmonary vascular effects of high dose tricyclic antidepressants: acute and chronic animal studies.

Overdose of tricyclic antidepressants, which inhibit cellular serotonin (5-HT) uptake, sometimes causes acute respiratory syndrome-like symptoms. Their acute and chronic cardiopulmonary actions, which might be implicated, utilising both in vivo and ex vivo animal studies, were investigated in this study. Acute amitriptyline (AMI), iprindole and imipramine caused dose-dependent prolonged rises in pulmonary artery pressure and oedema in anaesthetised cats in vivo. Acute AMI, in isolated ex vivo blood-perfused rat lungs, also caused dose-dependent sustained vasoconstriction, which could be attenuated with either calcium channel inhibition or a nitric oxide donor. It was demonstrated that the pressor effects of AMI were not due to release of histamine, serotonin, noradrenaline, or the activities of cycloxygenase or lipoxygenase. After AMI, hypoxic pulmonary vasoconstriction and the pressor actions of 5-HT and noradrenaline were diminished, possibly due to uptake inhibition. Activities of the endothelial-based enzymes, nitric oxide synthase and endothelin-converting enzyme, were undiminished. Large acute doses of AMI caused oedema with rupture of capillaries and alveolar epithelium. Chronic iprindole raised pulmonary artery pressure and right ventricle (RV)/left ventricle (LV) + septal (S) weight. Chronic AMI led to attenuation of the pressor action of 5-HT, especially when associated with chronic hypoxic-induced pulmonary hypertension. RV/LV+S weight increased, attributable to LV decline. The acute and chronic effects observed might have relevance to clinical overdose, while the attenuation of acute effects offers possible therapeutic options.

Acute Disease↗
PubMed2002

Multiple molecular targets of indole-3-carbinol, a chemopreventive anti-estrogen in breast cancer.

The mechanism of action of the anti-estrogen indole-3-carbinol (I3C), present in cruciferous vegetables, is being examined in our laboratory with a view to promote the use of this naturally occurring chemopreventive as an alternative to synthetic anti-estrogens in human breast cancer. Our previous results clearly demonstrated that despite its low affinity for the estrogen receptor (ER), I3C abrogated estradiol-mediated cellular and biochemical effects in estradiol-responsive cells and tissues. In an earlier report, we identified ER phosphorylation as one of the targets of I3C, and in this communication we describe the consequence of inhibition of ER phosphorylation. Estradiol-induced DNA-binding proteins that bound to several DNA-responsive elements were inhibited by I3C and this effect was not at the level of DNA-protein physical interaction as inclusion of I3C in vitro in the reaction mix did not affect the binding. We analyzed the spectrum of genes induced by estradiol and modulated and/or intercepted by I3C. Our results conclude that although estradiol-mediated functions are affected by I3C, its biochemical targets are multiple and some of these may be modulated by the oligomeric products of I3C.

Anticarcinogenic Agents↗
PubMed2001

The p38 MAPK pathway is involved in the IL-2 induction of TNF-beta gene via the EBS element.

As an important cytokine of the immune system, interleukin-2 (IL-2) can induce the expression of various genes, one of which is the tumor necrosis factor-beta (TNF-beta). However, the induction mechanism of TNF-beta remains to be fully explored. We have previously shown JAK-STAT pathway mediates TNF-beta gene induction upon IL-2 stimulation through an upstream -200GAS element. In this study, we further demonstrated that there is another essential -130EBS element in TNF-beta gene promoter region. Using IL-2-dependent cell line BAF/BO3beta, we found that this -130EBS element can form a specific complex with nuclear protein, which contained a novel ETS transcription factor. Furthermore, using kinase inhibitors, we revealed that p38 MAP kinase is involved in the formation of -130EBS-protein complex and the subsequent transcriptional activation of TNF-beta gene in response to IL-2 stimulation. Taken together, our results suggested that the complicated IL-2 induction of TNF-beta gene expression requires not only the activation of JAK-STAT pathway on the -200GAS element, but also the cooperation of another signal pathway on the -130EBS element.

Animals↗
PubMed2001

"Heavy electron" photoelectron spectroscopy: rotationally resolved ion pair imaging of CH3+.

We applied the velocity map imaging technique under high-resolution conditions to study ion pair products of the vacuum ultraviolet photodissociation of methyl chloride. We obtained rotationally resolved kinetic energy release spectra that directly provide vibrational frequencies and rotational constants of the fundamental carbocation, CH3+. The technique is analogous to photoelectron spectroscopy, with the chloride anion playing the role of a "heavy electron." The approach shows promise as a general probe of ionic species not amenable to study by traditional methods.

Journal Article↗
PubMed2001

Coronary smooth muscle differentiation from proepicardial cells requires rhoA-mediated actin reorganization and p160 rho-kinase activity.

We recently reported that the first detectable expression of SMC-specific proteins during coronary smooth muscle cell (CoSMC) differentiation from isolated proepicardial cells was restricted to cells undergoing epithelial-to-mesenchymal transformation (EMT). The objectives of this study were to examine more closely the relation between actin cytoskeletal rearrangements and serum response factor (SRF)-dependent transcription, and to specifically test whether rhoA-GTPase signaling is required for CoSMC differentiation. We report here that PDGF-BB stimulates EMT and promotes SRF-dependent expression of SMC marker genes calponin, SM22alpha, and SMgamma(actin) (SMgammaA) in proepicardial cells. C3 exoenzyme or rhoGDI, inhibitors of rhoA signaling, blocked PDGF-BB-induced EMT, prevented actin reorganization into stress fibers, and inhibited CoSMC differentiation. Incubation with the selective p160 rho-kinase (p160RhoK) inhibitor Y27632 (RKI) blocked EMT, prevented the appearance of calponin and SMgammaA-positive cells, and abolished expression and nuclear localization of SRF. To test the role of RhoK signaling for CoSMC differentiation in vivo, quail proepicardial organs (PEOs) were pretreated with RKI or vehicle and then grafted into age-matched host chick embryos to produce a chimeric epicardium. The ability of grafted cells to participate in coronary vessel formation was monitored by staining with antibodies for quail cell nuclear antigen and SMC marker proteins. Proepicardial cells pretreated with RKI failed to form CoSMCs in vivo. Time course studies traced this deficiency to a failure of epicardial-derived mesenchymal cells to migrate into or survive within the myocardium. In summary, these data point to important roles for rhoA-RhoK signaling in molecular pathways controlling cytoskeletal reorganization, SRF-dependent transcription, and cell survival that are required to produce CoSMCs from proepicardial cells.

Actins↗
PubMed2001

General approach for the synthesis of sarpagine/macroline indole alkaloids. Enantiospecific total synthesis of the indole alkaloid trinervine.

[structure: see text] The total synthesis of the indole alkaloid trinervine 1 was accomplished in enantiospecific fashion in an overall yield of 20% (from the tetracyclic ketone 8) in 10 reaction vessels (12.5% from tryptophan methyl ester). The synthesis of the N(a)-H substituted macroline equivalent 2 was also completed in high yield via the same intermediate 13. The unique protection/hydroboration process developed here should provide a method to functionalize the C(19)-C(20) double bond in similar systems.

Animals↗
PubMed2001

Phylogenetic comparison of classical swine fever virus in China.

An N-terminal fragment of the E2 gene of classical swine fever (CSF) virus encoding major immunogenic sites was amplified by RT-PCR directly from 110 clinical specimens representing 109 epizootic sites during the last decade in China. Phylogenetic relationships between these viruses as well as 20 reference strains were determined by comparison of their nucleotide sequences. A phylogenetic tree showed that 103 of the 110 field viruses (93.6%) were clustered within group 2 and subdivided into three subgroups, while the remaining seven viruses (6.4%), along with two Chinese reference strains, Shimen and HCLV (attenuated vaccine strain), were clustered into subgroup 1.1 within group 1. However, none of the Chinese CSF viruses were members of subgroup 1.2 (represented by reference strain Brescia). This is the first report on the distribution of CSF virus genotypes in China. Results indicated that CSF viruses predominating in recent epizootics within China are genetically divergent from the reference strain Shimen and the vaccine strain HCLV.

Animals↗
PubMed2001

Modeling of the separation of the enantiomers of 1-phenyl-1-propanol on cellulose tribenzoate.

The competitive adsorption isotherms of rac-1-phenyl-1-propanol on cellulose tribenzoate were measured by competitive frontal analysis. The experimental data were fitted to four different isotherm models: Langmuir, Bilangmuir, Langmuir-Freundlich, and Tóth. The fittings of the experimental data to all four models were satisfactory. It was excellent in the case of the Langmuir-Freundlich and the Tóth models. Overloaded elution profiles calculated with the Tóth isotherm were in good agreement with the experimental profiles in all the different experimental conditions investigated. This work extends to the case of binary mixtures the equivalence between the general rate and the lumped pore diffusion models already demonstrated for pure compounds when the ratio between the Stanton and the Biot numbers exceeds 5. The adsorption energy distribution for the Tóth isotherm was also calculated.

Journal Article↗
PubMed2001

Distinct phosphorylation patterns underlie Akt activation by different survival factors in neurons.

The survival of cultured cerebellar granule neurons can be maintained by depolarizing levels of potassium (high K(+), HK), insulin-like growth factor (IGF-1), cyclic AMP or lithium. We examined the possibility that the signaling pathways activated by these different factors converge and that Akt might represent such a point of convergence. Consistent with this possibility, we find that Akt is phosphorylated and activated by all four survival factors. The pattern of Akt phosphorylation induced by the four survival factors, however, shows differences. While IGF-1 induces phosphorylation of Akt at both Ser473 and Thr308, HK and cyclic AMP stimulate phosphorylation at Thr308 only. Lithium increases phosphorylation at Ser473 but not at Thr308. Our results are consistent with the possibility that Akt is a central component of different survival-promoting pathways in granule neurons. The different phosphorylation patterns, however, point to a previously unappreciated complexity in the regulation of Akt activity in neurons. Finally, we provide evidence indicating that SGK, a kinase that is structurally related to Akt, is also activated by the four survival factors.

Animals↗
PubMed2001

Adenovirus-mediated heme oxygenase-1 gene delivery inhibits injury-induced vascular neointima formation.

BACKGROUND: Recent studies have demonstrated that systemic pharmacological induction of heme oxygenase-1 (HO-1), the inducible isoform of the initial and rate-limiting enzyme for heme catabolism, attenuates neointima formation after experimental vascular injury. We have now investigated the ability of localized adenovirus-mediated HO-1 (Ad-HO-1) gene delivery to modify arterial remodeling after balloon angioplasty. METHODS AND RESULTS: Two weeks after balloon angioplasty in the rat carotid artery, elevated HO-1 protein was observed in the Ad-HO-1 arteries compared with those exposed to empty adenovirus (Ad-E) or to PBS. The arteries exposed to Ad-HO-1 exhibited significantly reduced neointimal area, medial wall area, neointimal area/medial wall area ratio, and neointimal thickness compared with arteries exposed to Ad-E. The Ad-E vessels showed subtle reductions in each morphometric parameter compared with PBS vessels. In a separate group of animals, concomitant treatment of Ad-HO-1 with the HO-1 inhibitor tin protoporphyrin completely restored each morphometric parameter to control levels. Arteries exposed to Ad-HO-1 demonstrated significantly increased TUNEL labeling of apoptotic nuclei and significantly decreased PCNA labeling of DNA synthesis in the medial wall 48 hours after injury. CONCLUSIONS: These results indicate that HO-1 represents an important in vivo vasoprotective mediator that is capable of attenuating the pathophysiological remodeling response to endovascular injury and suggest that HO-1 may be a novel target for the treatment of vascular disease.

Adenoviridae↗
PubMed2001

Timing of cognitive deficits following neonatal seizures: relationship to histological changes in the hippocampus.

Neonatal seizures are frequently associated with cognitive impairment and reduced seizure threshold. Previous studies in our laboratory have demonstrated that rats with recurrent neonatal seizures have impaired learning, lower seizure thresholds, and sprouting of mossy fibers in CA3 and the supragranular region of the dentate gyrus in the hippocampus when studied as adults. The goal of this study was to determine the age of onset of cognitive dysfunction and alterations in seizure susceptibility in rats subjected to recurrent neonatal seizures and the relation of this cognitive impairment to mossy fiber sprouting and expression of glutamate receptors. Starting at postnatal day (P) 0, rats were exposed to 45 flurothyl-induced seizures over a 9-day period of time. Visual-spatial learning in the water maze and seizure susceptibility were assessed in subsets of the rats at P20 or P35. Brains were evaluated for cell loss, mossy fiber distribution, and AMPA (GluR1) and NMDA (NMDAR1) subreceptor expression at these same time points. Rats with neonatal seizures showed significant impairment in the performance of the water maze and increased seizure susceptibility at both P20 and P35. Sprouting of mossy fibers into the CA3 and supragranular region of the dentate gyrus was seen at both P20 and P35. GluR1 expression was increased in CA3 at P20 and NMDAR1 was increased in expression in CA3 and the supragranular region of the dentate gyrus at P35. Our findings indicate that altered seizure susceptibility and cognitive impairment occurs prior to weaning following a series of neonatal seizures. Furthermore, these alterations in cognition and seizure susceptibility are paralleled by sprouting of mossy fibers and increased expression of glutamate receptors. To be effective, our results suggest that strategies to alter the adverse outcome following neonatal seizures will have to be initiated during, or shortly following, the seizures.

Animals↗
PubMed2001

Vasopressin differentially modulates noradrenaline release in the rat supraoptic nucleus.

Vasopressin is released not only from axon terminals in the neurohypophysis but also from soma/dendrite regions in the supraoptic nucleus. In order to investigate presynaptic roles of dendritically released vasopressin, we examined effects of local application of vasopressin upon noradrenaline release within the supraoptic nucleus by a microdialysis method. Noradrenaline release within the supraoptic nucleus was facilitated by local perfusion with high K+ or an NMDA receptor antagonist. Vasopressin augmented noradrenaline increase after high K+ but reduced it after an NMDA receptor antagonist, AP-5. The results suggest that dendritically released vasopressin modulates noradrenaline release within the supraoptic nucleus in a bimodal fashion.

Animals↗