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Biomedical subjects

L Q Chen

Publications and source records attributed to L Q Chen.

At least 19 recordsLinked to original sources
PubMed2006

Probing nanoscale ferroelectricity by ultraviolet Raman spectroscopy.

We demonstrated that ultraviolet Raman spectroscopy is an effective technique to measure the transition temperature (Tc) in ferroelectric ultrathin films and superlattices. We showed that one-unit-cell-thick BaTiO3 layers in BaTiO3/SrTiO3 superlattices are not only ferroelectric (with Tc as high as 250 kelvin) but also polarize the quantum paraelectric SrTiO3 layers adjacent to them. Tc was tuned by approximately 500 kelvin by varying the thicknesses of the BaTiO3 and SrTiO3 layers, revealing the essential roles of electrical and mechanical boundary conditions for nanoscale ferroelectricity.

Journal Article↗
PubMed2004

Room-temperature ferroelectricity in strained SrTiO3.

Systems with a ferroelectric to paraelectric transition in the vicinity of room temperature are useful for devices. Adjusting the ferroelectric transition temperature (T(c)) is traditionally accomplished by chemical substitution-as in Ba(x)Sr(1-x)TiO(3), the material widely investigated for microwave devices in which the dielectric constant (epsilon(r)) at GHz frequencies is tuned by applying a quasi-static electric field. Heterogeneity associated with chemical substitution in such films, however, can broaden this phase transition by hundreds of degrees, which is detrimental to tunability and microwave device performance. An alternative way to adjust T(c) in ferroelectric films is strain. Here we show that epitaxial strain from a newly developed substrate can be harnessed to increase T(c) by hundreds of degrees and produce room-temperature ferroelectricity in strontium titanate, a material that is not normally ferroelectric at any temperature. This strain-induced enhancement in T(c) is the largest ever reported. Spatially resolved images of the local polarization state reveal a uniformity that far exceeds films tailored by chemical substitution. The high epsilon(r) at room temperature in these films (nearly 7,000 at 10 GHz) and its sharp dependence on electric field are promising for device applications.

Journal Article↗
PubMed2002

Multiscale modeling of precipitate microstructure evolution.

We demonstrate how three "state-of-the-art" techniques may be combined to build a bridge between atomistics and microstructure: (1) first-principles calculations, (2) a mixed-space cluster expansion approach, and (3) the diffuse-interface phase-field model. The first two methods are used to construct the driving forces for a phase-field microstructural model of theta'- Al2Cu precipitates in Al: bulk, interfacial, and elastic energies. This multiscale approach allows one to isolate the physical effects responsible for precipitate microstructure evolution.

Journal Article↗
PubMed2002

Apoptosis in Barrett's oesophagus following antireflux surgery.

BACKGROUND: Intestinal metaplasia persists in Barrett's mucosa despite control of reflux. Tissue homeostasis is maintained by the balance between apoptosis and proliferation. There is an unexplained temporary increase in proliferation in patients with Barrett's mucosa after antireflux surgery, and the long-term effect of any therapy in altering this balance remains unclear. The aim of this study was to assess apoptosis in Barrett's oesophagus following antireflux surgery. METHODS: Apoptosis was evaluated in endoscopic biopsy specimens from 19 patients with Barrett's oesophagus 4 years after Collis-Nissen gastroplasty using an in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) method. RESULTS: Intestinal metaplasia had a lower apoptosis index than gastric metaplasia (0.27 versus 2.14 per cent; P < 0.001). After operation there was a steady increase of apoptosis in intestinal metaplasia over time (from 0.23 per cent before operation to 0.42 per cent within 2 years and to 0.59 per cent 4 years after operation; P = 0.015). Patients with persistent acid exposure did not show any increase in apoptosis in comparison with patients without acid exposure (0.41 versus 0.59 per cent; P = 0.91). CONCLUSION: Apoptosis is less in intestinal metaplasia than in gastric metaplasia, although there is an increase after antireflux surgery. Persistent acid reflux may predispose to malignancy.

Apoptosis↗
PubMed2001

Proliferative activity in Barrett's esophagus before and after antireflux surgery.

OBJECTIVE: To assess proliferation in the columnar-lined esophageal mucosa before and after antireflux surgery. SUMMARY BACKGROUND DATA: Intestinal metaplasia persists in Barrett's mucosa after reflux control. It remains at risk for uncontrolled cellular proliferation and adenocarcinoma formation. METHODS: Forty-five patients with Barrett's esophagus had a mean follow-up of 4 years after a Collis-Nissen gastroplasty. Proliferative activity was assayed immunohistochemically for Ki-67 expression in 73 preoperative and 176 postoperative biopsies. Correlation with manometric and 24-hour pH results was obtained. RESULTS: The Collis-Nissen gastroplasty restored the median lower esophageal sphincter gradient from 5.5 mmHg before surgery to 14.5 mmHg at 24 months and 12.9 mmHg at 48 months after surgery. The median esophageal acid exposure was reduced from 8% to 1% and 1% of recording time, respectively. The median Ki-67 labeling index increased from 28.5% before surgery to 36.1% at 12 to 23 months. It returned to preoperative level (26.9%) at 24 to 47 months. After surgery, abnormal intraesophageal acid exposure was documented in 12 patients but could not be correlated with sphincter pressure. After surgery, the pattern of proliferation in patients with acid exposure less than 4% in their esophagus showed significant differences when compared with the proliferation pattern of patients where abnormal intraesophageal acid exposure was recorded. New present dysplasia was observed only in patients with abnormal acid exposure. CONCLUSIONS: In Barrett's mucosa, from preoperative values, proliferation peaked early after surgery and then decreased to preoperative levels. Despite sphincter restoration and global reflux control, abnormal esophageal acid exposure persisted in 12 patients. Patients with abnormal esophageal acid exposure displayed more proliferation and more dysplasia.

Adult↗
PubMed2001

Assessing the potential for the stomatal characters of extant and fossil Ginkgo leaves to signal atmospheric CO2 change.

The stomatal density and index of fossil Ginkgo leaves (Early Jurassic to Early Cretaceous) have been investigated to test whether these plant fossils provide evidence for CO(2)-rich atmosphere in the Mesozoic. We first assessed five sources of natural variation in the stomatal density and index of extant Gingko biloba leaves: (1) timing of leaf maturation, (2) young vs. fully developed leaves, (3) short shoots vs. long shoots, (4) position in the canopy, and (5) male vs. female trees. Our analysis indicated that some significant differences in leaf stomatal density and index were evident arising from these considerations. However, this variability was considerably less than the difference in leaf stomatal density and index between modern and fossil samples, with the stomatal index of four species of Mesozoic Ginkgo (G. coriacea, G. huttoni, G. yimaensis, and G. obrutschewii) 60-40% lower than the modern values recorded in this study for extant G. biloba. Calculated as stomatal ratios (the stomatal index of the fossil leaves relative to the modern value), the values generally tracked the CO(2) variations predicted by a long-term carbon cycle model confirming the utility of this plant group to provide a reasonable measure of ancient atmospheric CO(2) change.

Journal Article↗
PubMed2000

Regulation of asymmetric smooth muscle myosin II molecules.

The emerging view of smooth/nonmuscle myosin regulation suggests that the attainment of the completely inhibited state requires numerous weak interactions between components of the two heads and the myosin rod. To further examine the nature of the structural requirements for regulation, we engineered smooth muscle heavy meromyosin molecules that contained one complete head and truncations of the second head. These truncations eliminated the motor domain but retained two, one, or no light chains. All constructs contained 37 heptads of rod sequence. None of the truncated constructs displayed complete regulation of both ATPase and motility, reinforcing the idea that interactions between motor domains are necessary for complete regulation. Surprisingly, the rate of ADP release was slowed by regulatory light chain dephosphorylation of the truncated construct that contained all four light chains and one motor domain. These data suggest that there is a second step (ADP release) in the smooth muscle myosin-actin-activated ATPase cycle that is modulated by regulatory light chain phosphorylation. This may be part of the mechanism underlying "latch" in smooth muscle.

Adenosine Diphosphate↗
PubMed2000

Clips versus suture technique: is there a difference?

INTRODUCTION: Coronary artery bypass grafting (CABG) is one of the most common procedures performed today, and wound complications are a major source of morbidity and cost. OBJECTIVE: To determine whether there is any difference in wound outcome (including cost in a Canadian context) between a subcuticular suture technique and skin stapling technique for closure of sternal and leg incisions in CABG patients. PATIENTS AND METHODS: One hundred and sixty-two patients undergoing CABG were prospectively, randomly placed to have their sternal and leg incisions closed with either a subcuticular suture technique or with a skin clip. Data were obtained through chart review, in-hospital assessments and follow-up visits. Nonblinded assessments were made regarding wound leakage, inflammation, infection, necrosis, swelling, dehiscence and cosmesis. Each of the parameters was graded on a scale from 1 to 4. The cost was evaluated in Canadian dollars. RESULTS: There were trends toward increased rates of in-hospital sternal (P=0.09) and leg (P=0.17) incision inflammation when the wounds were closed with skin clips. There was a significantly greater (P=0.05) rate of sternal wound infection with clips, as well as a tendency (P=0.15) toward a greater rate of mediastinitis at follow-up assessment. Cosmetic outcome was similar for both groups. The cost incurred was significantly greater when skin clips were used for closure. There was a greater than threefold difference, which translates to a greater than $10,000 difference over one year. CONCLUSIONS: Closure with a subcuticular technique achieves better outcomes than the use of skin clips. When factoring in the increased cost incurred by using clips, as well as other intangible factors such as surgical skill acquisition, subcuticular suture closure appears to be a favourable method of wound closure in CABG patients compared with the use of skin stapling techniques.

Aged↗
PubMed1999

Myosin VI is an actin-based motor that moves backwards.

Myosins and kinesins are molecular motors that hydrolyse ATP to track along actin filaments and microtubules, respectively. Although the kinesin family includes motors that move towards either the plus or minus ends of microtubules, all characterized myosin motors move towards the barbed (+) end of actin filaments. Crystal structures of myosin II (refs 3-6) have shown that small movements within the myosin motor core are transmitted through the 'converter domain' to a 'lever arm' consisting of a light-chain-binding helix and associated light chains. The lever arm further amplifies the motions of the converter domain into large directed movements. Here we report that myosin VI, an unconventional myosin, moves towards the pointed (-) end of actin. We visualized the myosin VI construct bound to actin using cryo-electron microscopy and image analysis, and found that an ADP-mediated conformational change in the domain distal to the motor, a structure likely to be the effective lever arm, is in the opposite direction to that observed for other myosins. Thus, it appears that myosin VI achieves reverse-direction movement by rotating its lever arm in the opposite direction to conventional myosin lever arm movement.

Actins↗
PubMed1999

Results of the Collis-Nissen gastroplasty in patients with Barrett's esophagus.

BACKGROUND: Barrett's esophagus (BE) is an advanced stage of gastroesophageal reflux disease. Medical treatment and standard antireflux operations show a high failure rate. An elongated gastroplasty, wrapped by a total fundoplication should provide a tension-free repair with adequate protection against reflux. The aim of this study is to review the operative effects of a Collis-Nissen gastroplasty to treat reflux in Barrett's esophagus. METHODS: From January 1989 to December 1997, 45 patients with BE (38 men, 7 women) aged 53.5 years, underwent a Collis-Nissen gastroplasty. Mean follow-up is 35.9 months (range, 6 to 110 months). Pre- and postoperative evaluations included symptom assessment, esophagogram, endoscopy, manometry, 24-hour pH study, and esophageal emptying scintigrams. RESULTS: There were no operative deaths. All reflux symptoms were controlled. Acid reflux was significantly reduced (percent time exposure decreased from 10% to 1%) and lower esophageal sphincter (LES) pressure were restored to normal (LES gradient increased from 4 mm Hg to 11 mm Hg). LES incomplete relaxation was noted in 50% of patients postoperatively. Endoscopically, mucosal damage from reflux healed but the columnar mucosa with intestinal metaplasia persisted. CONCLUSIONS: The Collis-Nissen gastroplasty, in patients with BE, controls reflux disease, its symptoms, and the mucosal damage associated with this condition. It restores the LES gradient but increases the resistance to bolus transit. There is no regression of the abnormal mucosa despite reflux control.

Adult↗
PubMed1999

The treatment of Zenker's diverticula: a review.

A historical review reveals that the treatment of Zenker's diverticula has paralleled its presumed pathophysiology. With the development of technical facilities to better evaluate the pharyngoesophageal region, incomplete relaxation of the upper esophageal sphincter (UES) seems to represent the key element in the development of high pharyngeal pressures with a subsequent outpouching responsible for the diverticulum formation. Many studies have justified myotomy as an essential component in the treatment of pharyngoesophageal diverticula because it represents an efficient therapy with little morbidity. A diverticulopexy should be added for pouches between 1 and 4 cm and a diverticulectomy should be performed for sacs greater than 5 cm to expect the best relief of symptoms. Other treatment modalities have recently been used such as the endoscopic division of the common wall between the cervical esophagus and the diverticulum with either electrocautery (Dohlman's procedure), a laser, or a stapling device. This method is gaining popularity because it achieves a good clinical outcome, especially in high-risk patients. However, more studies are needed to confirm its long-term effectiveness.

Esophagoscopy↗
PubMed1999

Early detection of esophageal squamous cell carcinoma and its effects on therapy: an overview.

Squamous cell carcinoma of the esophagus shows a wide variation in incidence worldwide. It is the fifth leading cause of cancer-related death in men and usually diagnosed at an advanced stage with unsatisfactory therapeutic results. The techniques available for early detection of esophageal carcinoma are reviewed in this paper, as well as its overall effect on survival. For the time being, only surgical resection at a very early stage may improve survival of the disease. Esophageal cancer can be treated at an earlier stage when it is diagnosed by mass screening detection. However, despite a high survival rate at 5 years, local recurrences and distal metastases may still occur even 10 years after treatment. Prevention and therapeutic intervention at an earlier stage before the oncologic process has resulted in cancer changes is necessary to alter the natural evolution of the disease.

Carcinoma, Squamous Cell↗
PubMed1999

Coarsening kinetics from a variable-mobility Cahn-Hilliard equation: application of a semi-implicit Fourier spectral method.

An efficient semi-implicit Fourier spectral method is implemented to solve the Cahn-Hilliard equation with a variable mobility. The method is orders of magnitude more efficient than the conventional forward Euler finite-difference method, thus allowing us to simulate large systems for longer times. We studied the coarsening kinetics of interconnected two-phase mixtures using a Cahn-Hilliard equation with its mobility depending on local compositions. In particular, we compared the kinetics of bulk-diffusion-dominated and interface-diffusion-dominated coarsening in two-phase systems. Results are compared with existing theories and previous computer simulations.

Journal Article↗
PubMed1997

Restoration of fast inactivation in an inactivation-defective human heart sodium channel by the cysteine modifying reagent benzyl-MTS: analysis of IFM-ICM mutation.

It has been suggested that the region linking domain III and IV of voltage-gated sodium channels forms the inactivation gate. A combination of site-directed mutagenesis, cysteine covalent modification, and electrophysiological recording techniques was used to identify the role of the Phe1486, a conserved phenylalanine residue located in the III-IV linker of Na+ channels. This Phe1486 is part of a hydrophobic amino acid cluster (IFM) that was proposed to play an essential role in the fast inactivation of voltage-gated sodium channels. Expression in tsA201 cells of an altered human heart 1 Na+ channel (hH1/F1486C) in which Phe1486 was replaced by a cysteine is associated with the appearance of a residual current, a loss of voltage-dependence of the time constants of inactivation, a shift of the steady-state inactivation to more depolarized voltages, and a recovery from inactivation that is faster than the wild-type hH1. Exposure of the cytoplasmic surface of mutant F1486C to the methanthiosulfonate reagents, MTSEA, MTSET, and MTSES, further disrupted macroscopic inactivation, but exposure to MTSBN completely restores fast inactivation and the voltage-dependence of fast inactivation. These findings support the formulation that the IFM motif of the III-IV-linker of voltage-gated sodium channels serves as an essential component of the inactivation particle and that the phenyl group of Phe1486 may play a crucial role in inactivation gate closure.

Cell Line↗
PubMed1997

Modulation of the human cardiac sodium channel alpha-subunit by cAMP-dependent protein kinase and the responsible sequence domain.

1. In order to investigate the modulation of human hH1 sodium channel alpha-subunits by cAMP-dependent protein kinase (PKA), the channel was expressed in oocytes of Xenopus laevis. 2. Cytosolic injection of cAMP, as well as of SP-cyclic 3',5'-hydrogen phosphorothioate adenosine triethylammonium salt (SP-cAMPS, the S-diastereoisomeric configuration of the compound with respect to the phosphorus atom), resulted in a marked and significant increase in peak sodium current (INa,p). Cytosolic injections of RP-cyclic 3',5'-hydrogen phosphorothioate adenosine triethylammonium salt (RP-cAMPS; a compound inhibitory to PKA) had no effect on peak current. 3. Kinetic parameters of steady-state activation, inactivation and recovery from inactivation were unchanged following stimulation of PKA activity, but a 42 +/- 5% (mean +/- S.E.M.) increase in maximal sodium conductance (delta gmax) could account for the observed increase in INa,p. 4. A set of chimerical sodium channels made from portions of the human cardiac hH1 alpha-subunit and the rat skeletal muscle SkM1 alpha-subunit (which is not affected by PKA stimulation) was generated. These were used to localize the structural determinant in the hH1 sequence responsible for PKA modulation of hH1. From our data we conclude that the effects of PKA on hH1 are conferred by the large cytosolic loop interconnecting transmembrane domains I and II, which is not conserved among sodium channel subtypes.

Animals↗
PubMed1997

Differences in the binding sites of two site-3 sodium channel toxins.

Site-3 toxins from scorpion and sea anemone bind to Na channels and selectively inhibit current decay. Anthopleurins A and B (ApA and ApB, respectively), toxins found in the venom of the sea anemone Anthopleura xanthogrammica, bind to closed states of mammalian skeletal and cardiac Na channels with differing affinities which arise from differences in first-order toxin/channel dissociation rate constants, koff. Using chimera comprising domain interchanges between channel isoforms, we examined the structural basis of this differential affinity. Toxin/channel association rates, kon, were similar for both toxins and both parental channels. Domain 4 determined koff for ApA, while ApB dissociated from all tested chimera in a cardiac-like manner. To probe this surprising difference between two such closely related toxins, we examined the interaction of chimeric channels with a form of ApB in which the two nonconserved basic residues, Arg-12 and Lys-49, were converted to the corresponding neutral amino acids from ApA. In the chimera comprising domain 1 from the cardiac muscle isoform and domains 2-4 from the skeletal muscle isoform, toxin dissociated at a rate intermediate between those of the parental channels. We conclude that the differential component of ApA binding is controlled by domain 4 and that some component of ApB binding is not shared by ApA. This additional component probably binds to an interface between channel domains and is partly mediated by toxin residues Arg-12 and Lys-49.

Animals↗
PubMed1997

Effects of Tityus serrulatus scorpion toxin gamma on voltage-gated Na+ channels.

The effects of Brazilian scorpion Tityus serrulatus toxin gamma (TiTx gamma) were studied on voltage-gated Na+ channels from human heart (hHl) and rat skeletal muscle (rSkM1). The Na+ channels were expressed in Xenopus laevis oocytes, and Na+ currents were recorded using two-microelectrode voltage-clamp techniques. In control experiments, the threshold of activation of hH1 is more negative than that of rSkM1 by approximately 20 mV. The toxin induces a shift of the voltage dependence of activation toward more negative potential values and reduces the amplitude of the current when administered to rSkM1. In contrast, TiTx gamma has little discernible effect on the current-voltage curve for hH1 at 100 nmol/L. Chimeric channels formed from these two isoforms were constructed to localize the binding site of TiTx gamma on rSkM1. TiTx gamma shifts the activation of a chimera (SSHH) in which domains 1 (D1) and 2 (D2) derive from rSkM1 and domain 3(D3) and 4 (D4) derive from hH1. This finding suggests that the toxin acts on the activation of rSkM1 by binding either to D1 and/or D2. TiTx gamma shifted the activation of another chimera with D2-D3-D4 from rSkM1 (HSSS) toward more hyperpolarizing potentials and had no effect on the activation of other chimeras with only D1-D3-D4 from rSkM1 (SHSS) or only D3 from rSkM1 (HHSH). Finally, a chimera in which D2 is from rSkM1 and all others domains are from hH1 (HSHH) provides further compelling support for our hypothesis. TiTx gamma shifts the activation of this chimera toward more negative potential values. Thus, TiTx gamma action on chimeras segregates with the source of D2: when D2 is from rSkM1, the toxin affects activation. We infer that D2 plays an important role in the activation process of voltage-gated Na+ channels.

Amino Acid Sequence↗