Biomedical subjects

J Bai

Publications and source records attributed to J Bai.

At least 19 recordsLinked to original sources

PubMed2006

DYX1C1 functions in neuronal migration in developing neocortex.

Rodent homologues of two candidate dyslexia susceptibility genes, Kiaa0319 and Dcdc2, have been shown to play roles in neuronal migration in developing cerebral neocortex. This functional role is consistent with the hypothesis that dyslexia susceptibility is increased by interference with normal neural development. In this study we report that in utero RNA interference against the rat homolog of another candidate dyslexia susceptibility gene, DYX1C1, disrupts neuronal migration in developing neocortex. The disruption of migration can be rescued by concurrent overexpression of DYX1C1, indicating that the impairment is not due to off-target effects. Transfection of C- and N-terminal truncations of DYX1C1 shows that the C-terminal TPR domains determine DYX1C1 intracellular localization to cytoplasm and nucleus. RNAi rescue experiments using truncated versions of DYX1C1 further indicate that the C-terminus of DYX1C1 is necessary and sufficient to DYX1C1's function in migration. In conclusion, DYX1C1, similar to two other candidate dyslexia susceptibility genes, functions in neuronal migration in rat neocortex.

Analysis of Variance↗

PubMed2006

Tissue microarray analysis of human FRAT1 expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours.

The mechanisms involved in the pathogenesis of ovarian cancer are poorly understood, but evidence suggests that aberrant activation of Wnt/beta-catenin signalling pathway plays a significant role in this malignancy. However, the molecular defects that contribute to the activation of this pathway have not been elucidated. Frequently rearranged in advanced T-cell lymphomas-1 (FRAT1) is a candidate for the regulation of cytoplasmic beta-catenin. In this study, we developed in situ hybridisation probes to evaluate the presence of FRAT1 and used an anti-beta-catenin antibody to evaluate by immunohistochemistry the expression levels and subcellular localisation of beta-catenin in ovarian cancer tissue microarrays. Expression of FRAT1 was found in some human normal tissues and 47% of ovarian adenocarcinomas. A total of 46% of ovarian serous adenocarcinomas were positive for FRAT1 expression. Accumulation of beta-catenin in the nucleus and/or cytoplasm was observed in 55% ovarian adenocarcinomas and in 59% of serous adenocarcinomas. A significant association was observed in ovarian serous adenocarcinomas between FRAT1 and beta-catenin expression (P<0.01). These findings support that Wnt/beta-catenin signalling may be aberrantly activated through FRAT1 overexpression in ovarian serous adenocarcinomas. The mechanism behind the overexpression of FRAT1 in ovarian serous adenocarcinomas and its significance is yet to be investigated.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Cloning and characterization of protease inhibitor-like cDNAs from the Hessian fly mayetiola destructor (SAY).

Analysis of transcriptomes from the salivary glands and midgut of Hessian fly larvae Mayetiola destructor (say) identified a set of diverse cDNAs that encode proteins with a relatively high percentage (over 10%) of cysteinyl residues. Structural comparison of these putative proteins with known sequences in GenBank revealed that the positions of the cysteinyl residues in the identified proteins were highly conserved within a family of proteinase inhibitors despite very little overall sequence similarity. Phylogenetic analysis sorted this set of cDNAs into five different groups. To determine if these cDNAs indeed encode proteinase inhibitors, recombinant proteins were generated with two cDNAs from two different groups. Biochemical analysis of the recombinant proteins against commercial and insect gut proteinases demonstrated that the recombinant proteins are strong proteinase inhibitors with different specificities. Northern blot and real-time PCR analysis revealed that the different genes were expressed at different developmental stages and in different tissues. The overall results indicated that M. destructor contains a complex of genes that code for proteinase inhibitors which may regulate proteinase activities in different regulatory pathways. The GenBank accession numbers for the cDNAs in this paper were DQ232690 to DQ232718.

Amino Acid Sequence↗

PubMed2006

Ectopic cartilage formation induced by mesenchymal stem cells on porous gelatin-chondroitin-hyaluronate scaffold containing microspheres loaded with TGF-beta1.

The study aimed to produce a novel porous gelatin-chondroitin-hyaluronate scaffold in combination with a controlled release of TGF- beta1 and to evaluate its potentials in ectopic cartilage formation. The gelatin-chondroitin-hyaluronate scaffold was developed to mimic the natural extra cellular matrix of cartilage. Gelatin microspheres loaded with TGF- beta1 (MS-TGF beta1) showed a fast cytokine release at initial phase (37.4%) and the ultimate accumulated release was 83.1% by day 18. Then MS-TGF beta1 were incorporated into scaffold. The MSCs seeded on scaffold with or without MS-TGF beta1 were incubated in vitro or implanted subcutaneously in nude mice. In vitro study showed that, compared to the scaffold, the scaffold/MS-TGF beta1 significantly augmented the proliferation of MSCs and GAG synthesis. Three weeks postoperatively histology observation showed that in MSCs/scaffold/MS-TGF beta1 implantation group, cells of newly formed ectopic cartilage were located within typical lacunae and demonstrated morphological characteristics of chondrocytes. Six weeks later the ectopic cartilage grew more and islands of cartilage were observed. The matrix was extensively metachromatic by safranin-O/Fast green staining. Immunohistochemical staining also indicated ectopic cartilage was intensely stained for type II collagen. Instead, in the MSCs/scaffold implantation group, no cartilage-like tissue formed and matrix showed negative or weak positive staining. The percentage of positive staining area was significantly larger in MSCs/scaffold/MS-TGF beta1 group (p<0.05) at each time point. The results indicated that the novel gelatin-chondroitin-hyaluronate scaffold with MS-TGF beta1 could induce the chondral differentiation of MSCs to form cartilage and might serve as a new way to repair cartilage defects.

Animals↗

PubMed2005

Morphological instability in InAs/GaSb superlattices due to interfacial bonds.

Synchrotron x-ray diffraction is used to compare the misfit strain and composition in a self-organized nanowire array in an InAs/GaSb superlattice with InSb interfacial bonds to a planar InAs/GaSb superlattice with GaAs interfacial bonds. It is found that the morphological instability that occurs in the nanowire array results from the large misfit strain that the InSb interfacial bonds have in the nanowire array. Based on this result, we propose that tailoring the type of interfacial bonds during the epitaxial growth of III-V semiconductor films provides a novel approach for producing the technologically important morphological instability in anomalously thin layers.

Journal Article↗

PubMed2005

Step-controlled strain relaxation in the vicinal surface epitaxy of nitrides.

On-axis and vicinal GaN/AlN/6H-SiC structures grown under identical conditions have been studied by x-ray diffraction and transmission electron microscopy to demonstrate the distinctive features of vicinal surface epitaxy (VSE) of nitrides on SiC. In VSE, the epilayers are tilted from the substrate due to the out-of-plane lattice mismatch (Nagai tilts), and the in-plane mismatch strains are more relaxed. The majority of misfit dislocations (MDs) at the vicinal AlN/6H-SiC interface are found to be unpaired partial MDs that are geometrically necessary to correct the stacking sequences from 6H to 2H. This mechanism indicates that it is possible to develop "step-controlled-epitaxy" strategies to control strain relaxation by adjusting the substrate offcut angles.

Journal Article↗

PubMed2005

Melting temperature of ice Ih calculated from coexisting solid-liquid phases.

We carried out molecular-dynamics simulations by using the two-phase coexistence method with the constant pressure, particle number, and enthalpy ensemble to compute the melting temperature of proton-disordered hexagonal ice I(h) at 1-bar pressure. Four models of water were considered, including the widely used TIP4P [W. L. Jorgensen, J. Chandrasekha, J. D. Madura, R. W. Impey, and M. L. Klein, J. Chem. Phys.79, 926 (1983)] and TIP5P [M. W. Mahoney and W. L. Jorgensen J. Chem. Phys.112, 8910 (2000)] models, as well as recently improved TIP4P and TIP5P models for use with Ewald techniques-the TIP4P-Ew [W. Horn, W. C. Swope, J. W. Pitera, J. C. Madura, T. J. Dick, G. L. Hura, and T. Head-Gordon, J. Chem. Phys.120, 9665 (2004)] and TIP5P-Ew [S. W. Rick, J. Chem. Phys.120, 6085 (2004)] models. The calculated melting temperature at 1 bar is T(m) = 229 +/- 1 K for the TIP4P and T(m) = 272.0 +/- 0.6 K for the TIP5P ice I(h), both are consistent with previous simulations based on free-energy methods. For the TIP4P-Ew and TIP5P-Ew models, the calculated melting temperature is T(m) = 257.0 +/- 1.1 K and T(m) = 253.9 +/- 1.1 K, respectively.

Journal Article↗

PubMed2005

Optimum control of the Hemopump as a left-ventricular assist device.

A general framework for designing an optimum control strategy for the Hemopump is described. An objective function was defined that includes four membership functions, each constructed based on the desired values of one of the four members: stroke volume, mean left atrial pressure, aortic diastolic pressure and mean pump rotation speed. The Hemopump was allowed to operate either at a constant speed or at two different speeds during a cardiac cycle. The goal was to maximise the objective function by varying the magnitude and timing of the pump speed. Using a canine circulatory model, it was demonstrated that, in general, different cardiac conditions or different clinical objectives require different operation parameters. For example, when a left ventricle with minor ischaemia was simulated, and the main objective was to increase stoke volume, the objective function was maximised, from a value of 0.877 when the pump was off, to 0.946 when the pump was operated at speed 2 (18 500 revolutions min(-1)). On the other hand, for a severely ischaemic heart, the optimum pump speed became speed 3 (20 000 revolutions min(-1)), which maximized the objective function to 0.943 (from 0.707 when the pump was off). The results also suggest that it is more beneficial to operate the Hemopump at two different speeds during a cardiac cycle (a higher speed during systole and early diastole, and a lower speed during late diastole) than to maintain a constant speed throughout the cardiac cycle.

Animals↗

PubMed2004

Efficacy and safety of telmisartan vs. losartan in control of mild-to-moderate hypertension: a multicentre, randomised, double-blind study.

This multicentre, randomised, double-blind, double-dummy, parallel-group study compared the efficacy and safety of telmisartan with those of losartan after 8 weeks' treatment. In total, 330 patients with mild-to-moderate hypertension (systolic blood pressure [SBP] <180 mmHg; diastolic blood pressure [DBP] 95-109 mmHg) were randomly assigned to receive once-daily treatment with telmisartan 40 mg (n = 164) or losartan 50 mg (n = 166). After 4 weeks' treatment, if a patient's DBP was > or = 90 mmHg, the dose was increased to telmisartan 80 mg or losartan 100 mg, respectively. The results show that mean trough seated blood pressure was reduced significantly more in the telmisartan group than that in the losartan group (SBP 12.5 mmHg vs. 9.4 mmHg, p = 0.037; DBP 10.9 mmHg vs. 9.3 mmHg, p = 0.030). The overall DBP response rate (reduction from baseline in mean seated DBP > or = 10 mmHg and/or a mean seated DBP <90 mmHg) at the end of the study in the telmisartan group was higher than that in losartan group (70.1% vs. 58.7%, p = 0.020). At both the low and high doses, the DBP response rates for telmisartan were significantly higher than those for losartan (telmisartan 40 mg vs. losartan 50 mg: 46.3% vs. 32.5%, p = 0.010; telmisartan 80 mg vs. losartan 100 mg: 79.3% vs. 65.3%, p = 0.008). Adverse events with the two treatments were comparable (telmisartan vs. losartan 23.2% vs. 22.9%, p = 0.952). Most events were mild in intensity and abated within 72 h. Thus, telmisartan 40 mg or 80 mg administered once daily can reduce SBP and DBP effectively and safely.

Adolescent↗

PubMed2004

Effects of high intensity focused ultrasound on vascular endothelial growth factor in melanoma bearing mice.

This study was to investigate the effects of high intensity focused ultrasound on vascular endothelial growth factor. A B16 melanoma model was adopted in our study. Melanoma bearing mice were randomly divided into two groups: HIFU group and surgery group. While the control group was only injected with isovolumetric normal saline solution and treated as the surgery group. We detected VEGF both in tissues and sera through immunohistochemical method and ELISA respectively. Tissues were sampled pre- and at the 3rd day post-operation in HIFU group and blood samples were taken pre- and at the 1st, 3rd, and 7th day post-operation in all the groups. As a result, in the tissues, VEGF was expressed in 80% melanomas, but none was detected in the targeted area after HIFU treatment. In the sera, there was a decreasing tendency of serum-VEGF concentrations in group HIFU and surgery after operation, while that in the control group increased after operation. The levels in the HIFU group on day 1, 3, and 7 postoperatively were all lower than that in the surgery group respectively (79.16 pg/ml vs 91.59 pg/ml; 33.64 pg/ml vs 49.39 pg/ml; 30.37 pg/ml vs 46.68 pg/ml), but there wasn't any significant difference (P > 0.05). So HIFU can destroy VEGF in the targeted area and maybe have less of an effect on serum-VEGF than surgery.

Animals↗

PubMed2003

A randomised clinical trial of high-intensity focused ultrasound ablation for the treatment of patients with localised breast cancer.

High-intensity focused ultrasound (HIFU) is a noninvasive treatment that induces complete coagulative necrosis of a tumour at depth through the intact skin. This study was to explore the possibility of using HIFU for the treatment of patients with localised breast cancer in a controlled clinical trial. A total of 48 women with biopsy-proven breast cancer (T(1-2), N(0-2), M0) were randomised to the control group in which modified radical mastectomy was performed, and the HIFU group in which an extracorporeal HIFU ablation of breast cancer was followed by modified radical mastectomy. Short-term follow-up, pathologic and immunohistochemical stains were performed to assess the therapeutic effects on tumour and complications of HIFU. The results showed that no severe side effect was observed in the HIFU-treated patients. Pathologic findings revealed that HIFU-treated tumour cells underwent complete coagulative necrosis, and tumour vascular vessels were severely damaged. Immunohistochemical staining showed that no expression of PCNA, MMP-9, and CD44v6 was detected within the treated tumour cells in the HIFU group, indicating that the treated tumour cells lost the abilities of proliferation, invasion, and metastasis. It is concluded that, as a noninvasive therapy, HIFU could be effective, safe, and feasible in the extracorporeal treatment of localised breast cancer.

Adult↗

PubMed2003

Layer ordering and faulting in (GaAs)n/(AlAs)n ultrashort-period superlattices.

We report studies of (GaAs)(n)/(AlAs)(n) ultrashort-period superlattices using synchrotron x-ray scattering. In particular, we demonstrate that interfaces of these superlattices contain features on two different length scales: namely, random atomic mixture and ordered mesoscopic domains. Both features are asymmetric on the two interfaces (AlAs-on-GaAs and GaAs-on-AlAs) for n>2. Periodic compositional stacking faults, arising from the intrinsic nature of molecular-beam epitaxy, are found in the superlattices. In addition, the effect of growth interruption on the interfacial structure is discussed. The relevant scattering theory is developed to give excellent fits to the data.

Journal Article↗

PubMed2003

Simulation study of the effects of hypovolaemia on cardiovascular response to orthostatic stress.

To investigate the role played by hypovolaemia in the mechanism of orthostatic intolerance, a mathematical model was developed. The model consisted of seven sub-models that describe: the redistribution of blood induced by lower body negative pressure (LBNP); filling of the left ventricle; contracting of the left ventricle; interaction between the left ventricle and peripheral circulation; and baroreflex regulation. The model was evaluated using experimental data. Using the model, computer simulations were performed to investigate the effects of hypovolaemia on the cardiovascular response to LBNP. The simulation results indicated that, first, when the blood loss is less than 5%, blood pressure can be maintained in the normal range by the baroreflex regulatory mechanism, even with high LBNP application; secondly, when the blood loss is between 15 and 20%, heart rate and blood pressure can be kept in the normal range if LBNP is not applied, but blood pressure falls sharply with LBNP application; and, thirdly, when the blood loss is 25%, the cardiovascular system is in an unstable state (heart rate: 116 beat min (-1), systolic blood pressure: 97 mmHg; diastolic blood pressure: 77 mmHg), even without any LBNP, and becomes more unstable with LBNP. The simulation results support the hypothesis that hypovolaemia is a cause of orthostatic intolerance.

Adult↗

PubMed2003

Adaptive approximation of the boundary surface of a neuron in confocal microscopy volumetric images.

In biomedical visualisation, the isosurface is usually used to represent (approximate) the boundary surface of the structure within biomedical volumetric images. However, in many confocal microscopy volumetric images of neurons, the grey values of the object and/or background are usually uneven. Therefore a fixed isosurface is not suitable for use in approximating the boundary surface of the neuron. A method is proposed to construct the adaptively approximating surface of the boundary surface of the neuron. In this method, the boundary surface of the neuron could be locally and adaptively approximated with different surface patches in different local regions. Consequently, the approximation accuracy has been considerably improved.

Algorithms↗

PubMed2002

Simulation study of the Hemopump as a cardiac assist device.

A dynamic model was developed for a Hemopump that withdraws blood from the left ventricle and discharges it to the aorta through a miniature axial-flow pump. Incorporation of the Hemopump model in a previously established model for the canine circulatory system enabled the effects of the Hemopump on various haemodynamic variables of the circulatory system to be studied, and the benefit of the Hemopump to the failing heart was investigated. In addition, the influence of the physiological status of the right ventricle on the Hemopump performances was examined, and the synchronous and non-synchronous operations of the Hemopump were compared. Results verified that the Hemopump assists the failing heart by increasing the oxygen supply, while reducing the oxygen consumption of the heart through a reduction in the workload of the left ventricle. These beneficial effects were enhanced when the pump's rotation speed was increased. When pump speed was increased from 17,000 to 23,000 revolutions min-1, the oxygen supply increased 101%, and the oxygen consumption decreased 60%. However, when the pump rotation speed was too high, the inflow to the pump could be impaired and the pump performance could be negatively affected. Predications from the model were in good agreement with the results previously obtained in animal experiments and in vitro measurements.

Animals↗

PubMed2002

Novel ultrasonic fusion imaging method based on cyclic variation in myocardial backscatter.

Quantitative ultrasonic tissue characterisation of the myocardium based on integrated backscatter (IB) has the potential of becoming an effective method for detecting and evaluating myocardial ischaemia. To facilitate IB-based clinical applications, a new imaging method has been developed that combines the anatomical information of a B-mode image with the contractile performance of a selected myocardial region. To produce such a fusion image, a region of interest (ROI) in a B-mode cardiac image was first selected by the user. Algorithms for detection of the endocardium and epicardium were developed, and the resulting mean distance between the computer-detected curve and the manually traced curve was 0.83mm for the endocardium and 0.58mm for the epicardium. The cyclic variation of IB (CVIB) of each myocardial tissue element within the ROI was then calculated over one cardiac cycle. Finally, a grey-scale B-mode image at the end of diastole was displayed as a still image, and the pixels representing the myocardial tissue in the ROI colour-coded according to the corresponding CVIB over the past heart cycle. Both the B-mode image and the colour-coded region were refreshed (up-dated) at the next end-of-diastole. Preliminary results from normal (CVIB= 10-12dB) and ischaemic (CVIB = 5-7 dB) canine hearts are presented that demonstrate the utility of this new imaging method.

Diagnosis, Computer-Assisted↗

PubMed2001

CYP2E1-dependent toxicity and oxidative stress in HepG2 cells.

Induction of CYP2E1 by ethanol is one of the central pathways by which ethanol generates a state of oxidative stress in hepatocytes. To study the biochemical and toxicological actions of CYP2E1, our laboratory established HepG2 cell lines which constitutively overexpress CYP2E1 and characterized these cells with respect to ethanol toxicity. Addition of ethanol or an unsaturated fatty acid such as arachidonic acid or iron was toxic to the CYP2E1-expressing cells but not control cells. This toxicity was associated with elevated lipid peroxidation and could be prevented by antioxidants and inhibitors of CYP2E1. Apoptosis occurred in the CYP2E1-expressing cells exposed to ethanol, arachidonic acid, or iron. Removal of GSH caused a loss of viability in the CYP2E1-expressing cells even in the absence of added toxin or pro-oxidant. This was associated with mitochondrial damage and decreased mitochondrial membrane potential. Surprisingly, CYP2E1-expressing cells had elevated GSH levels, due to transcriptional activation of gamma glutamyl cysteine synthetase. Similarly, levels of catalase, alpha-, and microsomal glutathione transferase were also increased, suggesting that upregulation of these antioxidant genes may reflect an adaptive mechanism to remove CYP2E1-derived oxidants. While it is likely that several mechanisms contribute to alcohol-induced liver injury, the linkage between CYP2E1-dependent oxidative stress, mitochondrial injury, and GSH homeostasis may contribute to the toxic action of ethanol on the liver. HepG2 cell lines overexpressing CYP2E1 may be a valuable model to characterize the biochemical and toxicological properties of CYP2E1.

Animals↗

PubMed2001

Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis.

Thioredoxin (Trx), a redox enzyme with a conserved active site (Cys-32-Gly-Pro-Cys-35), is induced and secreted into circulation in response to inflammation. Studies here demonstrate that elevating Trx levels in circulation either by i.v. injection of recombinant Trx or stimulating Trx release in Trx-transgenic mice dramatically blocks lipopolysaccharide (LPS)-stimulated neutrophil migration in the murine air pouch chemotaxis model. Furthermore, we show that leukocyte recruitment induced by the murine chemokines KC/GROalpha, RANTES (regulated upon activation, normal T cell expressed and secreted), and monocyte chemoattractant protein-1 (MCP-1) is suppressed also in Trx-transgenic mice. Addressing the mechanism responsible for this suppression, we show that circulating Trx blocks (i) the LPS-stimulated in vitro activation of neutrophil p38 mitogen-activated protein kinase, (ii) the normal down-regulation of CD62L on neutrophils migrating into the LPS-stimulated air pouch, and (iii) the in vitro adhesion of LPS-activated neutrophils on endothelial cells. However, as we also show, Trx does not alter the expression of endothelial cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, CD62P, and CD62E) within 3 h. Collectively, these findings indicate that elevated levels of circulating Trx interfere with chemotaxis by acting directly on neutrophils. We discuss these findings in the context of recent studies reporting beneficial effects of acutely elevated Trx in ischemic injury and negative effects associated with chronically elevated Trx in HIV disease.

Animals↗