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Biomedical subjects

Y Liang

Publications and source records attributed to Y Liang.

At least 37 records · Page 2Linked to original sources

Modulation of gene expression by alloimmune networks following murine heart transplantation.

The objective of our study was to analyze gene expression profiles in a complex in vivo model of solid organ transplantation, and to investigate the effects of single-gene deletions on alloimmunity. Using algorithms to generate dendrograms and self-organizing maps, we differentiated the alloimmune profiles of 16 transgenic knockout mouse strains, and identified subsets of genes that correlate with the duration of graft survival and provide candidates for prognostic and diagnostic indicators following transplantation in our model system.

Algorithms↗

Potential applications of nicotinic ligands in the laboratory and clinic.

The nicotinic acetylcholine receptor (nAChR) is a receptor, ion channel complex composed of five polypeptide subunits. There are many different nAChR subtypes constructed from a variety of different subunit combinations. This structural diversity contributes to the varied roles of nAChRs in the peripheral and central nervous system, and this diversity offers an excellent opportunity for chemists who are producing ligands. Subunit specific ligands could have wide and varied effects in the laboratory as experimental tools and in the clinic as therapeutic agents. Because presynaptic nAChRs have been shown to enhance the release of many neurotransmitters, new nicotinic ligands that potentiate nAChR activity would be very useful. Such ligands could enhance the release of various neurotransmitters during degenerative diseases that cause neurotransmitter systems to decrease their output. For example, boosting the release from cholinergic neurons would help patients with Alzheimer's disease, and boosting the release from dopaminergic neurons would help patients with Parkinson's disease.

Alzheimer Disease↗

Prostaglandin ethanolamides (prostamides): in vitro pharmacology and metabolism.

We investigated whether prostaglandin ethanolamides (prostamides) E(2), F(2alpha), and D(2) exert some of their effects by 1) activating prostanoid receptors either per se or after conversion into the corresponding prostaglandins; 2) interacting with proteins for the inactivation of the endocannabinoid N-arachidonoylethanolamide (AEA), for example fatty acid amide hydrolase (FAAH), thereby enhancing AEA endogenous levels; or 3) activating the vanilloid receptor type-1 (TRPV1). Prostamides potently stimulated cat iris contraction with potency approaching that of the corresponding prostaglandins. However, prostamides D(2), E(2), and F(2alpha) exhibited no meaningful interaction with the cat recombinant FP receptor, nor with human recombinant DP, EP(1-4), FP, IP, and TP prostanoid receptors. Prostamide F(2alpha) was also very weak or inactive in a panel of bioassays specific for the various prostanoid receptors. None of the prostamides inhibited AEA enzymatic hydrolysis by FAAH in cell homogenates, or AEA cellular uptake in intact cells. Furthermore, less than 3% of the compounds were hydrolyzed to the corresponding prostaglandins when incubated for 4 h with homogenates of rat brain, lung, or liver, and cat iris or ciliary body. Very little temperature-dependent uptake of prostamides was observed after incubation with rat brain synaptosomes or RBL-2H3 cells. We suggest that prostamides' most prominent pharmacological actions are not due to transformation into prostaglandins, activation of prostanoid receptors, enhancement of AEA levels, or gating of TRPV1 receptors, but possibly to interaction with novel receptors that seem to be functional in the cat iris.

Amides↗

Measurement of the electric form factor of the neutron at Q2=0.5 and 1.0 GeV2/c2.

The electric form factor of the neutron was determined from measurements of the d-->(e-->,e'n)p reaction for quasielastic kinematics. Polarized electrons were scattered off a polarized deuterated ammonia (15ND3) target in which the deuteron polarization was perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle detector. We find G(n)(E)=0.0526+/-0.0033(stat)+/-0.0026(sys) and 0.0454+/-0.0054+/-0.0037 at Q(2)=0.5 and 1.0 (GeV/c)(2), respectively.

Journal Article↗

Baseline Na-Li countertransport and risk of hypertension in children: a 10-year prospective study in Hanzhong children.

Sodium-lithium countertransport (Na-Li CT) is associated with blood pressure (BP) and in many cross-sectional investigations and some longitudinal studies, essential hypertension has been proposed as a biochemical marker or predictor of hypertension risk in adults. The present study investigated prospectively whether baseline Na-Li CT rate was an index of increased risk of future development of hypertension in children. At baseline visit in 1987 of the Hanzhong Children Hypertension Study comprising 4000 school children aged 5-6 years old, 310 samples were randomly selected for measurement of baseline Na-Li CT rate; we made a 10-year follow-up of them in the same season in 1997. This cohort of children is the sample for analysis in the present report. Baseline Na-Li CT rate was positively correlated to systolic BP (SBP) both in baseline and follow-up (baseline, gamma=0.21, P<0.05; follow-up, gamma=0.32, P<0.01), and positively correlated to diastolic BP (DBP) (gamma=0.20, P<0.05) and body mass index (gamma=0.18, P<0.05) in follow-up examination. Longitudinal analysis of 10-year BP evolution, children in higher baseline Na-Li CT (ie, >260 micromoll RBC/h) had greater BP change than children in lower baseline Na-Li CT (ie, </=260 mumol/l RBC/h) (SBP, 15.8+/-12.9 vs 19.3+/-13.1, DBP 8.8+/-11.2 and 11.3+/-10.6, P<0.05). Multiple logistic regression analysis showed that children in the higher Na-Li CT (>260 mumol/l RBC/h) were associated with approximately 1.5 times greater risk of high BP) in comparison to placement in lower Na-Li CT (</=260 mumol/l RBC/h). Elevated baeline RBC Na-Li countertransport could be a risk predictor predisposing to the development of hypertension in children.

Antiporters↗

Bimatoprost: a novel antiglaucoma agent.

The aim of glaucoma therapy is to preserve vision by reducing intraocular pressure (IOP). Following recent National Eye Institute sponsored studies, it is becoming increasingly apparent that every mmHg of extra IOP lowering counts. Bimatoprost is the newest and most effective addition to the physician's armamentarium of ocular hypotensive drugs. Direct clinical comparisons have demonstrated that it is more efficacious than the prostaglandin (PG) FP receptor agonist prodrugs, latanoprost and travoprost, as well as a beta-adrenoceptor antagonist, timolol, alone or in fixed combination with the carbonic anhydrase inhibitor, dorzolamide. Moreover, patients that are refractory to latanoprost therapy may be successfully treated with bimatoprost. Such evidence provides support, at the clinical level, for the contention that bimatoprost is pharmacologically distinct from PG FP receptor agonist prodrugs. Bimatoprost is a structural analog of PGF2alpha-ethanolamide (prostamide F2alpha), which is formed from the endocannabinoid anandamide by a biosynthetic pathway involving cyclooxygenase-2 (COX-2). Their pharmacology is remarkably similar, such that bimatoprost may be regarded as a prostamide mimetic. The target receptor for bimatoprost and the prostamides appears unique and unrelated to PG- and endocannabinoid-sensitive receptors. Extensive ocular distribution/metabolism studies in non-human primates demonstrate that bimatoprost is not a prodrug, it remains essentially intact. Its profound ocular hypotensive effects may, therefore, be attributed to its prostamide-mimetic properties.

Amides↗

Characteristics of electron heat transport of plasma with an electron internal-transport barrier in the large helical device.

Associated with the transition from ion root to electron root, an electron internal transport barrier (ITB) appears in the large helical device, when the heating power of electron cyclotron resonance heating exceeds the threshold power. The incremental thermal diffusivity of electron heat transport chi(inc)(e) in the ITB plasma is much lower than that in the plasma with the heating power below the threshold, and the thermal diffusivity chi(e) decreases with increasing of heating power [dchi(e)/d(P/n(e))<0] in helical ITB plasmas.

Journal Article↗

High resolution spectroscopy of the 12Lambda B hypernucleus produced by the (e,e'K+) reaction.

High-energy, cw electron beams at new accelerator facilities allow electromagnetic production and precision study of hypernuclear structure, and we report here on the first experiment demonstrating the potential of the (e,e'K+) reaction for hypernuclear spectroscopy. This experiment is also the first to take advantage of the enhanced virtual photon flux available when electrons are scattered at approximately zero degrees. The observed energy resolution was found to be approximately 900 keV for the (12)(Lambda)B spectrum, and is substantially better than any previous hypernuclear experiment using magnetic spectrometers. The positions of the major excitations are found to be in agreement with a theoretical prediction and with a previous binding energy measurement, but additional structure is also observed in the core excited region, underlining the future promise of this technique.

Journal Article↗

Pharmacological characterization of a novel antiglaucoma agent, Bimatoprost (AGN 192024).

Replacement of the carboxylic acid group of prostaglandin (PG) F(2alpha) with a nonacidic moiety, such as hydroxyl, methoxy, or amido, results in compounds with unique pharmacology. Bimatoprost (AGN 192024) is also a pharmacologically novel PGF(2alpha) analog, where the carboxylic acid is replaced by a neutral ethylamide substituent. Bimatoprost potently contracted the feline lung parenchymal preparation (EC(50) value of 35-55 nM) but exhibited no meaningful activity in a variety of PG-sensitive tissue and cell preparations. Its activity seemed unrelated to FP receptor stimulation according to the following evidence. 1) Bimatoprost exhibited no meaningful activity in tissues and cells containing functional FP receptors. 2) Bimatoprost activity in the cat lung parenchyma is not species-specific because its potent activity in this preparation could not be reproduced in cells stably expressing the feline FP receptor. 3) Radioligand binding studies using feline and human recombinant FP receptors exhibited minimal competition versus [(3)H]17-phenyl PGF(2a) for Bimatoprost. 4) Bimatoprost pretreatment did not attenuate PGF(2alpha)-induced Ca(2+) signals in Swiss 3T3 cells. 5) Regional differences were apparent for Bimatoprost but not FP agonist effects in the cat lung. Bimatoprost reduced intraocular pressure in ocular normotensive and hypertensive monkeys over a 0.001 to 0.1% dose range. A single-dose and multiple-dose ocular distribution/metabolism studies using [(3)H]Bimatoprost (0.1%) were performed. Within the globe, bimatoprost concentrations were 10- to 100-fold higher in anterior segment tissues compared with the aqueous humor. Bimatoprost was overwhelmingly the predominant molecular species identified at all time points in ocular tissues, indicating that the intact molecule reduces intraocular pressure.

Amides↗

Spatial and temporal organic and heavy metal pollution at Mai Po Marshes Nature Reserve, Hong Kong.

An intensive monthly sampling of water and sediments from 12 sites over 8 months covering wet and dry seasons at Mai Po Marshes Nature Reserve was conducted during June 1997-February 1998. Major organic (C, N and P) and heavy metal pollutants (Cd, Cr, Cu, Ni, Pb, Zn) water and sediment samples were examined. The results showed that Mai Po Marshes were severely polluted by organic matter and heavy metals, and the water from Deep Bay appeared to be the source of pollution. Up to 13-55% chance that the sediments of Mai Po Marshes were classified as moderately to seriously metal contaminated materials, according to the guideline set by Hong Kong Government. Empirical models describing organic matter and heavy metal spatial and seasonal dynamics in the water and sediments were formulated, based on data analysis. During wet season (June-October), more than 58% variations of total P can be explained by ortho-P in water, while ammonia-N explained up to 90% variations of total Kjeldahl nitrogen in water. Throughout the whole sampling period (June-February), there were significant correlations (p<0.01) between total organic C in water. pH in the sediments and salinity in water appeared to be important factors determining heavy metal mobility in sediments, while potential metal release from the sediments is a concern when any oxidizing processes such as flooding or dredging are imposed on sediments.

Carbon↗

Early events in Bcl-2-enhanced apoptosis.

Transfection of PC12 pheochromocytoma cells with bcl-2 potentiates apoptosis induced by the antimitotic agent, neocarzinostatin (NCS). The mechanism of potentiation involves caspase 3-dependent cleavage of Bcl-2 to its pro-apoptotic counterpart, but the cellular events proximal to caspase 3 activation in this system are not known. Two min after initiation of NCS treatment, Bax begins to translocate from cytosol to the mitochondria; the mitochondrial localization of Bax persists for 30 min after NCS treatment. At the same time, cytochrome C is released from the mitochondria to cytosol. The mitochondrial membrane potential exhibits differential change in mock- and bcl-2 -transfected PC12 cells. In mock-transfected PC12 cells, the mitochondrial membrane potential increases immediately, peaks at 15 min following initiation of NCS treatment, and drops thereafter. In contrast, in bcl-2 -transfected PC12 cells, the membrane potential drops immediately following NCS treatment. Caspase 9 is activated and peaks at 10 min in both mock- and bcl-2 transfected PC12 cells, however, the peak activity of caspase 9 is higher and caspase 9 activation lasts longer (30 min) after the treatment in bcl-2 transfectants. Not until 30 min after initiation of a 1 h treatment with NCS is Bcl-2 protein cleaved in bcl-2 -transfected cells. Thus, in bcl-2 -transfected cells, the mitochondrial membrane potential drops and cytochrome C is released from the mitochondria despite the presence of large amounts of intact mitochondrial Bcl-2. This makes it unlikely that cleavage of Bcl-2 is the only factor involved in potentiation of NCS-induced apoptosis by Bcl-2.

Animals↗

Island dynamics in the large-helical-device plasmas.

In the Large Helical Device plasma discharges, the size of an externally imposed island with mode number ( n/m = 1/1) decreases substantially when the plasma is collisionless ( nu(*)< approximately 1) and the beta is finite ( > approximately 0.1%) at the island location. For the collisional plasmas with finite beta, on the other hand, the size of the island increases. However, there is a threshold in terms of the vacuum island size below which the island enlargement is not seen.

Journal Article↗

The chemical syntheses and bioactivities of novel peptide-based endothelin antagonists.

Endothelin antagonists, novel tripeptides containing a series of unnatural amino acids, were synthesized and characterized. A linear peptide BQ-485, perhydroazepin-1-yl-L-leucyl (1)-D-tryptophanyl (2)-D-tryptophan (3), was selected as the parent compound. The introduction of D-Phe derivatives into these peptidic ET antagonists resulted in potent activity against the contraction of rat aortic smooth muscles induced by ET-1 (10 nM) which activated the ET receptors. Among these compounds, 15 tripeptides had high enough antagonistic activity at the level of 10(-7) mol/L (IC50). The activity of three compounds was 10(-6) mol/L (IC50). These HIM-CO-Leu-D-Trp-D-Phe(-R)-OH compounds as ETA antagonists may provide a tool for the development of therapeutic agents in the treatment of putative ET-1-related disorders.

Animals↗

Examining the relationship between cancer invasion/metastasis and drug resistance.

Studies of cancer invasion/metastasis and drug resistance have in the past generally proceeded along the separate pathways of research. Recently, however, interest has been focused on the possible relationship between drug resistance and cancer invasion and metastasis. A relationship between these two phenotypes has been demonstrated by two types of observation: firstly, some tumor cells selected for resistance to drugs are more invasive/metastatic relative to non-resistant parental cells; secondly, in some cases, secondary (more metastatic) tumors are more resistant to chemotherapeutic drugs than their primary counterparts. In other instances reported in the literature, no correlation is seen between drug exposure/resistance and cancer invasion/metastasis. The possibility that treatment with some chemotherapeutic drugs may be able to promote cancer invasion and metastasis needs further investigation because of its potential clinical relevance. A better understanding of any relationship between drug resistance and cancer invasion could lead to more effective cancer treatment.

Animals↗

Clinical characteristics of acute ischemic syndrome in China.

OBJECTIVE: To analyse the characteristics and therapies of patients with acute ischemic syndrome in China. METHODS: This study is part of the international multicentre registry for acute ischemic syndrome. Since April 1999, the data of patients admitted to designated hospitals with acute ischemic cardiac chest pain were collected by filling in Case Report Forms offered by the Canadian Cardiovascular Collaboration. The main clinica l characteristics and in hospital events of the patients were recorded. RESULTS: Fifteen hundred and nine cases of acute ischemic syndrome from 34 hospitals nationwide were enrolled in the registry (including unstable angina and non Q-wave myocardial infarction). The mean age of the patients was 62.3. Male dominance (62.2%) was noted. The percentages of patients with chest pain at presentation and abnormal ECG were 47.8% and 89.5%, respectively. The most common clinical diagnosis on admission was unstable angina, accounting for 91.3% of the patients and non Q-wave myocardial infarction (MI), accounting for the other 8.7%. During hospitalization, the following interventions were given: thrombolytic therapy in 50 cases (3.3%), coronary angiography in 528 cases (35.0%), percutaneous transluminal coronary angioplasty (PTCA) in 253 cases (16.8%) and coronary artery bypass graft surgery (CABG) in 62 cases (4.1%). Nitrate (oral or patch ) and anti-platelet therapy were used in 1460 cases (96.8%) and 1441 cases (95.5%), respectively. The incidence of in hospital major events was 18.8%, in cluding 18 deaths (1.2%), with the most common causes being severe arrhythmias and sudden death. CONCLUSIONS: Patients with acute ischemic syndrome in China have mostly been diagnosed as cases of unstable angina. A relatively high PTCA rate but low CABG rate was noted in China. The most common cause of in hospital death is severe arrhythmias or sudden death.

Adult↗

Changes of biophysical behavior of k562 cells for p16 gene transfer.

p16 gene was transferred into human erythroleukemia cell line K562 that had been subjected to p16 deletion. The changes of biophysical behavior of K562 cells after gene transfer were studied with the micropipette technique. The micropipette data were analyzed with a standard solid viscoelastic model. In comparison to untransfected control K562 cells and the cells transfected with an empty vector, the p16-transfected K562 cells showed an increase in the elastic element K(1), which is inversely proportional to the maximum deformation over a long period of time, whereas the viscous element mu and the other elastic element K(2) showed no significant difference. The results indicate that K562 cells became more rigid after p16 transfer. The p16-transfected K562 cells also had a higher surface charge density. This study contributes to our knowledge about the suppression effect of p16 gene on tumor cell migration and about its use in gene therapy.

Biophysical Phenomena↗

Observation of plasma flow at the magnetic island in the large helical device.

Radial profiles of ion temperature and plasma flow are measured at the n/m = 1/1 magnetic island produced by external perturbation coils in the Large Helical Device. The sheared poloidal flows and sheared radial electric field are observed at the boundaries of the magnetic island, because the poloidal flow vanishes inside the static magnetic island. When the width of the magnetic island becomes large, the flow along the magnetic flux surface inside the magnetic island appears around the O point in the direction which reduces the shear of the poloidal flow at the boundary of the magnetic island.

Journal Article↗