Search PubMed⌕ Search

Biomedical subjects

Z Wang

Publications and source records attributed to Z Wang.

At least 55 records · Page 3Linked to original sources

Atomic-scale imaging of wall-by-wall breakdown and concurrent transport measurements in multiwall carbon nanotubes.

We report the atomic-scale imaging with concurrent transport measurements of the breakdown of individual multiwall carbon nanotubes inside a transmission electron microscope equipped with a piezomanipulator. We found unexpectedly three distinct breakdown sequences: namely, from the outermost wall inward, from the innermost wall outward, and alternatively between the innermost and the outmost walls. Remarkably, a significant amount of current drop was observed when an innermost wall is broken, proving unambiguously that every wall is conducting. Moreover, the breakdown of each wall in any sequence initiates in the middle of the nanotube, not at the contact, proving that the transport is not ballistic.

Journal Article↗

Development of the right ventricular inflow tract and moderator band: a possible morphological and functional explanation for Mahaim tachycardia.

Atriofascicular accessory bundles with AV-node like conduction properties can sustain atrioventricular (AV) re-entrant tachycardia (Mahaim tachycardia). During early embryogenesis, the AV canal is situated above the primitive left ventricle (LV), and a right AV connection has not been achieved yet. We studied the formation of the right ventricular (RV) inflow tract in relation to the developing cardiac conduction system and hypothesized a morphological explanation for functional atriofascicular bypass tracts. Analysis of lacZ-expression during sequential stages of cardiogenesis was performed in CCS-lacZ transgenic mice (E9.5 to 15.5). Embryos were stained for beta-galactosidase activity and the myocardial marker HHF35. At early stages CCS-lacZ expression was observed in a ring surrounding the AV canal, which connected at the inner curvature to the primary fold. The first sign of formation of the (CCS-lacZ negative) RV inlet component was a groove in the CCS-lacZ positive tissue of the primary fold. Outgrowth of the RV inlet tract resulted in division of the primary fold in a septal part, the trabecula septomarginalis and a lateral part, the moderator band, which extended laterally up to the right AV ring. Electrophysiological measurements in embryonic hearts (E15.5) in which the right atrium (RA) and RV were isolated from the left atrium (LA) and LV supported the functionality of this AV-connection via the moderator band, by demonstrating sequential atrial and ventricular activation in both RA/RV and LA/LV preparations. In conclusion, our observations may provide a possible morphological and functional explanation for atriofascicular accessory pathways via the moderator band, underlying Mahaim tachycardia.

Animals↗

Optical phonon sidebands of electronic intersubband absorption in strongly polar semiconductor heterostructures.

We present the first evidence for a distinct optical phonon progression in the linear and nonlinear intersubband absorption spectra of electrons in a GaN/Al(0.8)Ga(0.2)N heterostructure. Femtosecond two-color pump-probe experiments in the midinfrared reveal spectral holes on different vibronic transitions separated by the LO-phonon frequency. These features wash out with a decay time of 80 fs due to spectral diffusion. The remaining nonlinear transmission changes decay with a time constant of 380 fs. All results observed are described by the independent boson model.

Journal Article↗

Confinement of a large number of antiprotons and production of an ultraslow antiproton beam.

We have used a radio frequency quadrupole decelerator to decelerate antiprotons emerging from the CERN Antiproton Decelerator from MeV- to keV-scale energy, and collected five decelerated pulses in a multiring trap. Some 5 x 10(6) antiprotons were stacked in this way. Cooling of the trapped antiprotons by a simultaneously trapped electron plasma was studied nondestructively via shifts in plasma mode frequencies. We have also demonstrated the first step in extracting a 10-500 eV antiproton beam from the trap.

Journal Article↗

The Biomolecular Interaction Network Database and related tools 2005 update.

The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular interactions that arise from published experimental research and to provide this information, as well as tools to enable data analysis, freely to researchers worldwide. BIND data are curated into a comprehensive machine-readable archive of computable information and provides users with methods to discover interactions and molecular mechanisms. BIND has worked to develop new methods for visualization that amplify the underlying annotation of genes and proteins to facilitate the study of molecular interaction networks. BIND has maintained an open database policy since its inception in 1999. Data growth has proceeded at a tremendous rate, approaching over 100 000 records. New services provided include a new BIND Query and Submission interface, a Standard Object Access Protocol service and the Small Molecule Interaction Database (http://smid.blueprint.org) that allows users to determine probable small molecule binding sites of new sequences and examine conserved binding residues.

Animals↗

Large dose ketamine inhibits lipopolysaccharide-induced acute lung injury in rats.

BACKGROUND: Sepsis is associated with the highest risk of progression to acute lung injury or the acute respiratory distress syndrome. Ketamine has been advocated for anesthesia in endotoxemic and other severely ill patients because it is a cardiovascular stimulant. Our study was designed to investigate the effect of ketamine on the endotoxin-induced acute lung injury in vivo. MATERIALS AND METHODS: Adult male Wistar rats were randomly divided into 6 groups: saline controls; rats challenged with endotoxin (5 mg/kg) and treated with saline; challenged with endotoxin (5 mg/kg) and treated with ketamine (0.5 mg/kg); challenged with endotoxin (5 mg/kg) and treated with ketamine (5 mg/kg); challenged with endotoxin (5 mg/kg) and treated with ketamine (50 mg/kg); saline injected and treated with ketamine (50 mg/kg). TNF-alpha, IL-6 and NF-kappa B were investigated in the tissues of the lung after 2 h. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated 6 h later. RESULTS: We demonstrated that intravenous administration of endotoxin could provoke significant lung injury, which was characterized by increase of MPO activity and wet/dry weight ratio, TNF-alpha and IL-6 expression and NF-kappa B activation. Ketamine (5, 50 mg/kg) inhibited endotoxin-induced NF-kappa B activation. Ketamine only at a dose of 50 mg/kg inhibited TNF-alpha and IL-6 production, and decreased MPO activity and wet/dry weight ratio after endotoxin challenge. CONCLUSIONS: Ketamine, only at a supra-anesthetic dosage, could inhibit endotoxin-induced pulmonary inflammation in vivo.

Animals↗

Laser surface modification of poly(epsilon-caprolactone) (PCL) membrane for tissue engineering applications.

Ultra-thin polycaprolactone (PCL) produced by bi-axial stretching was previously shown to have significant advantage for membrane tissue engineering. However, the permeability of the membrane needs to be enhanced. In this study, ablation experiments using femtosecond laser and excimer laser were carried out to modify the PCL surface. The use of the femtosecond laser produces neat drilled-through holes while the excimer laser is employed to produce blind-holes on the membrane. The modified surface of the membrane was studied and analyzed for different laser parameters (such as pulse energy and pulse repetition rate and characterized using several techniques that include optical microscopy, scanning electron microscopy and water contact angle measurements). Results showed that the morphological surface changes with different laser parameters, and the water contact angle decreases as the surface of the membrane is modified. The decrease in water contact angle suggests that surface of the membrane had become more hydrophilic than the non-laser treated membrane. The present study demonstrated that laser surface modification on the PCL can be achieved with high degree of success and precision. This paved the way for further enhancement in membrane tissue engineering.

Biocompatible Materials↗

Promotion of long-term heart allograft survival by combination of mobilized donor plasmacytoid dendritic cells and anti-CD154 monoclonal antibody.

Infusion of donor immature dendritic cells (DC) can significantly prolong survival of organ allografts, and this is believed to be due to antigen recognition by T cells in the absence of co-stimulation. In this study we report that a single pre-operative infusion of donor-mobilized immature plasmacytoid dendritic cells (pDCs) is superior to that of other DC sub-sets in suppressing allograft rejection. The combination of pDC infusion with injection of anti-CD154 monoclonal antibody further inhibited graft rejection and, in 50% of the mice, led to indefinite graft survival. This finding suggests a role for the plasmacytoid DC sub-set in facilitating organ transplant survival and also in the treatment of autoimmune disorders.

Animals↗

The role of mPer1 in morphine dependence in mice.

Investigations using Drosophila melanogaster have shown that the circadian clock gene period can influence behavioral responses to cocaine, and the mouse homologues, mPer1 and mPer2, modulate cocaine sensitization and reward. In the present study, we applied DNAzyme targeting mPer1 to interfere the expression of mPer1 in CNS in mice and studied the role of mPer1 on morphine dependence. We found that the DNAzyme could attenuate the expression of mPer1 in CNS in mice. Mice treated with DNAzyme and morphine synchronously did not show preference to the morphine-trained side, whereas the control group did. In contrast, mice treated with DNAzyme after morphine showed preference to the morphine-trained side as well as the control group did. These results indicate that drug dependence seems to be influenced at least partially by mPer1, but mPer1 cannot affect morphine dependence that has been formed.

Animals↗

Glucocorticoid receptor involvement in pair bonding in female prairie voles: the effects of acute blockade and interactions with central dopamine reward systems.

Induction of partner preferences in monogamous prairie voles (Microtus ochrogaster) was used to examine the possibility that blockade of glucocorticoid receptors may be rewarding in females of this species. We first examined the ability of either a mineralocorticoid receptor antagonist (spironolactone) or a glucocorticoid receptor antagonist (RU-486) to induce partner preferences in females. Peripheral administration of either of the antagonists was capable of inducing partner preferences, although the effective dose for RU-486 was an order of magnitude lower than that for spironolactone. We then examined a potential interaction of glucocorticoid receptor with central dopamine in pair bonding by treating females with i.c.v. dopamine receptor antagonists (haloperidol, SCH23390, or eticlopride) prior to peripheral administration of RU-486. All of the dopamine antagonists were capable of reversing the effects of glucocorticoid receptor blockade on pair bonding. These results establish the ability for acute blockade of glucocorticoid to induce pair bonds in female voles. Further, this effect appears to be mediated via an interaction with central dopamine systems. Together these findings support the possibility that, unlike other model systems, reductions in glucocorticoid receptor activity may enhance reward in female prairie voles.

Animals↗

Post-ischemic delivery of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor rosuvastatin protects against focal cerebral ischemia in mice via inhibition of extracellular-regulated kinase-1/-2.

After recent clinical trials, statins have gained increasing significance in secondary stroke prevention. From experimental studies, it is well established that statins have beneficial action when delivered prophylactically prior to a stroke. Conversely, much less is known about the effects of statins on injury development when delivered after ischemia. We here examined the effects of a post-ischemic delivery of rosuvastatin (0.5, 5 or 20 mg/kg, administered i.p. immediately after reperfusion onset), a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on brain injury and cell signaling after focal cerebral ischemia, induced by 90 min of intraluminal middle cerebral artery occlusion in mice. In animals receiving normal saline, 0.5 or 5 mg/kg rosuvastatin, middle cerebral artery occlusions resulted in reproducible brain infarcts at 24 h after reperfusion onset, which did not differ in size. However, rosuvastatin, administered at higher doses (20 mg/kg), reduced infarct volume at 24 and 48 h after ischemia (by 34+/-16% and 18+/-3%, respectively, P<0.05). Western blots revealed that rosuvastatin decreased phosphorylated extracellular-regulated kinase-1/-2 and reduced activated caspase-3 levels in ischemic brain areas, while endothelial NO synthase expression, p38 and Jun kinase phosphorylation were not influenced by the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Rosuvastatin also significantly diminished expression levels of inducible NO synthase in the ischemic brain. Our results indicate that rosuvastatin may have utility not only as stroke prophylaxis but also as acute therapy inhibiting executive cell death pathways.

Animals↗

Continuous transcatheter arterial thrombolysis for early hepatic artery thrombosis after liver transplantation.

Early hepatic artery thrombosis (HAT) after orthotopic liver transplantation remains a significant cause of graft loss and patient death. The most effective treatment approach is still controversial. The purpose of this study was to assess the effect of continuous transcatheter arterial thrombolysis in the treatment of early HAT. Routine posttransplant color Doppler imaging (CDI) was performed to monitor hepatic artery blood flow. HAT was confirmed by arterial angiography in suspected cases. HAT was identified in 8 patients (8/287, 2.8%) which occurred on days 2 to 19 (mean, 5.2 days) after liver transplantation. Patients with HAT were treated with continuous transcatheter arterial thrombolysis using urokinase. Successful revascularization through thrombolysis was obtained in all eight cases. One patient died of a pulmonary infection at 2 months after liver transplantation. Another patient underwent retransplantation because of resistant allograft rejection and recurrence of HAT 6 months after the first operation, but died from multiple system organ failure 2 months later. The other six patients remained in good health during the follow-up period of 3 to 27 months. Our results demonstrate that CDI is an effective method to monitor the occurrence of early HAT after liver transplantation. Furthermore, continuous transcatheter arterial thrombolysis with urokinase could be a rational therapeutic approach to rescue the allograft following early HAT diagnosis confirmed by arterial angiography.

Adult↗

A DNA recombination-based approach to eliminate papillomavirus infection.

At present, no treatments exist that effectively target and eliminate papillomaviruses (PVs) from infected cells or prevent its replication. We are employing a strategy to prevent virus replication in PV-infected cells through the conditional expression of the herpes simplex virus type 1 thymidine kinase (TK) gene. Expression of TK in this system is expected to be triggered by a homologous recombination event between the endogenous PV genome and a nonexpressing TK gene cassette. Recombination between these two DNAs is expected to change the nonexpressing cassette into a form that expresses TK. Various constructs were generated to express the TK in the above manner. Transfection of cell lines with a TK nonexpressing plasmid did not result in TK production due to alternative splicing and polyadenylation site selection. However, cotransfection of cell lines with PV plasmids along with the above TK construct containing short segments of PV sequences resulted in a recombination event that led to TK expression as shown by Northern and Western blot analyses. We also developed a TK expression cassette utilizing an adeno-associated virus (AAV) vector. Delivery of the cassette by AAV to PV-infected cells resulted in TK expression, and ganciclovir treatment resulted in efficient killing of these cells.

Antiviral Agents↗

Efficient gene delivery to human and rodent islets with double-stranded (ds) AAV-based vectors.

Transplantation of allogeneic pancreatic islets is an effective approach to treat type 1 diabetes. To bypass the need for systemic administration of immunosuppression drugs following transplantation, approaches to genetically modify allogeneic islets to express anti-inflammatory, immunosuppressive, or antiapoptotic proteins prior to transplantation are being developed. Adeno-associated viral (AAV) based vectors have been used for gene transfer to islets, but the efficiency of functional transduction is low. Recently, double-stranded (ds) or double-copy (dc) based AAV vectors have been developed that allow for more rapid and efficient AAV-mediated transgene expression following transduction. Here we demonstrate that intact human and murine islets can be transduced with dsAAV2-eGFP efficiently compared to single-stranded AAV2-eGFP. Furthermore, our results demonstrate that murine islets transduced with dsAAV2-eGFP have normal islet glucose responsiveness, viability, and islet insulin content. Transplantation of the dsAAV2-eGFP transduced islet restored normal glycemia in diabetic mice without eliciting an immune response. Significant dsAAV2-mediated eGFP expression was observed in the islet grafts for at least 6 months post-transplant. Finally, we demonstrated that dsAAV serotypes 2, 6, and 8 infect human islets efficiently. Taken together, these results suggest that dsAAV based vectors are highly appropriate for gene transfer to islets to facilitate transplantation.

Animals↗

Low physical activity levels of modern Homo sapiens among free-ranging mammals.

Obesity prevalence rates are increasing worldwide and one prevailing hypothesis is that physical activity levels of modern humans are markedly reduced compared to those of our Paleolithic ancestors. We examine this hypothesis by deriving relative activity energy expenditure from available doubly labeled water and indirect calorimetry data in free-ranging non-human mammals. Our results, given the constraints posed by limited data availability, suggest that a low physical activity level, much less than that observed in free-ranging non-human mammals or highly active humans, is present in modern adult humans living within advanced settings. Our observations lend support to the hypothesis that low activity-related energy expenditure levels contribute to the rising worldwide prevalence of obesity.

Animals↗