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Biomedical subjects

S Wang

Publications and source records attributed to S Wang.

At least 55 records · Page 3Linked to original sources

Field-effect characteristics and screening in double-walled carbon nanotube field-effect transistors.

Field-effect transistors (FETs) have been fabricated using double-walled carbon nanotubes (DWCNTs), and electrical transport measurements have been carried out on 125 DWCNT FETs. Among these devices, 52 were found to show basically semiconducting field-effect characteristics, 44 show metallic characteristics, and 29 show neither pure semiconducting nor metallic characteristics. These 3 distinct types of field-effect characteristics were identified as resulting from the semiconducting (S)-S, metallic (M)-M or M-S, and S-M combinations of the two shells of the DWCNT. While the S-S and M-M or M-S DWCNT devices exhibit similar field-effect characteristics to those by single-walled carbon nanotube (SWCNT) devices, the S-M device responds uniquely to the external gate voltage. In particular, it was found that free charges in the inner metallic shell may screen the outer semiconducting shell from the gate effect and that the screening is directly related to the intershell interaction, which increases with increasing temperature and tube diameter. The screening is disadvantageous to the performance of DWCNT FETs, and a similar effect is expected to occur in MWCNTs.

Journal Article↗

Identification and analysis of tumour-associated antigens in hepatocellular carcinoma.

To identify tumour and tumour-associated antigens in patients with hepatocellular carcinoma (HCC) one may find potential diagnostic markers and immunotherapeutic targets. In the current study, 30 distinct antigens reactive with serum IgG from HCC patients were identified by serological analysis of cDNA expression libraries (SEREX). The mRNA expression patterns of 14 of these 30 antigens were altered in cancer as further revealed by cDNA microarray, with upregulation for nine and downregulation for five antigens. One of the upregulated antigens was cancer-testis (CT) antigen (CAGE), which had been previously reported to be expressed exclusively in normal gametogenic tissues and aberrantly expressed in a variety of cancer cells. In our study, CAGE mRNA was expressed in 39.4% of HCC patients, 73.3% of patients with gastric cancer and 30.8% of patients with colorectal cancer. Antibodies against CAGE protein were detected in approximately 5.1% of the sera from HCC patients, 8.3% of that from gastric cancer patients and 7.3% of that from colorectal cancer patients. The relative high incidence of CAGE in cancer cells makes it a potential target for vaccine design. Another antigen of great interest is transgelin 2. The overexpression of transgelin 2 mRNA in a large per cent (69%) of HCC points to its potential as a diagnostic marker for HCC.

Antigens, Neoplasm↗

Improved neuronal transgene expression from an AAV-2 vector with a hybrid CMV enhancer/PDGF-beta promoter.

BACKGROUND: Adeno-associated virus type 2 (AAV-2) vectors are highly promising tools for gene therapy of neurological disorders. After accommodating a cellular promoter, AAV-2 vectors are able to drive sustained expression of transgene in the brain. This study aimed to develop AAV-2 vectors that also facilitate a high level of neuronal expression by enhancing the strength of a neuron-specific promoter, the human platelet-derived growth factor beta-chain (PDGF) promoter. METHODS AND RESULTS: A hybrid promoter approach was adopted to fuse the enhancer of human cytomegalovirus immediately early (CMV) promoter to the PDGF promoter. In cultured cortex neurons, AAV-2 vectors containing the hybrid promoter augmented transgene expression up to 20-fold over that mediated by titer-matched AAV-2 vectors with the PDGF promoter alone and 4-fold over the CMV enhancer/promoter. Injection of AAV-2 vectors with the hybrid promoter into the rat striatum resulted in neuron-specific transgene expression, the level of which was about 10-fold higher than those provided by the two control AAV-2 expression cassettes at 4 weeks post-injection and maintained for at least 12 weeks. Gene expression in the substantia nigra through possible retrograde transport of the AAV-2 vectors injected into the striatum was not obvious. After direct injection of AAV-2 vectors into the substantia nigra, transgene expression driven by the hybrid promoter was observed specifically in dopaminergic neurons and its level was about 3 and 17 times higher than that provided by the PDGF promoter alone and the CMV enhancer/promoter, respectively. CONCLUSIONS: Enhanced transgene capacity plus neuron-specificity of the AAV-2 vectors developed in this study might prove valuable for gene therapy of Parkinson's disease.

Animals↗

Double-antigen sandwich ELISA for detection of antibodies to SARS-associated coronavirus in human serum.

The study presented here was conducted to evaluate the performance of a double-antigen sandwich ELISA to detect antibodies in human serum against the coronavirus associated with severe acute respiratory syndrome (SARS). A recombinant partial nucleocapsid protein of SARS-associated coronavirus was used as a serodiagnostic antigen in the ELISA. A total of 2892 clinical serum samples were tested with the ELISA kit, which positively identified 25 of 35 (71.4%) samples of patients with confirmed SARS infection, 286 of 407 (70%) samples of patients suspected of having SARS, 229 of 302 (75.8%) samples of convalescent SARS patients, and 0 of 544 samples obtained from healthcare workers; only 1 of 1604 clinical samples obtained from patients with other diseases demonstrated a weakly positive result. These results indicate that the double-antigen sandwich ELISA is an effective screening method for the serodiagnosis of SARS-associated coronavirus.

Antibodies, Viral↗

Disease-associated fibronectin matrix fragments trigger anoikis of human primary ligament cells: p53 and c-myc are suppressed.

Inflammation in periodontal disease is characterized by the breakdown of the extracellular matrix. This study shows that an inflammation-associated matrix breakdown fragment of fibronectin (FN) induces anoikis of human periodontal ligament (PDL) cells. This 40 kDa fragment was identified in human inflammatory crevicular fluid and is associated with disease status. Previously, we reported that a similar recombinant FN fragment triggered apoptosis of PDL cells by an alternate apoptotic signaling pathway that requires transcriptional downregulation of p53 and c-myc. Thus, to determine whether the physiologically relevant 40 kDa fragment triggers apoptosis in these cells, the 40 kDa fragment was generated and studied for its apoptotic properties. The 40 kDa fragment induces apoptosis of PDL cells, and preincubation of cells with intact vitronectin, FN, and to a limited extent collagen I, rescue this apoptotic phenotype. These data suggest that the 40 kDa fragment prevents PDL cell spreading, thereby inducing anoikis. The signaling pathway also involves a downregulation in p53 and c-myc, as determined by Western blotting and real time quantitative PCR. These data indicate that an altered FN matrix as is elaborated in inflammation induces anoikis of resident cells and thus may contribute to disease progression.

Anoikis↗

Effects of steroidal glycoalkaloids from potatoes (Solanum tuberosum) on in vitro bovine embryo development.

alpha-Solanine and alpha-chaconine are two naturally occurring steroidal glycoalkaloids in potatoes (Solanum tuberosum), and solanidine-N-oxide is a corresponding steroidal aglycone. The objective of this research was to screen potential cyto-toxicity of these potato glycoalkaloids using bovine oocyte maturation, in vitro fertilization techniques and subsequent embryonic development as the in vitro model. A randomized complete block design with four in vitro oocyte maturation (IVM) treatments (Experiment 1) and four in vitro embryo culture (IVC) treatments (Experiment 2) was used. In Experiment 1, bovine oocytes (n=2506) were matured in vitro in medium supplemented with 6 microM of alpha-solanine, alpha-chaconine, solanidine-N-oxide or IVM medium only. The in vitro matured oocytes were then subject to routine IVF and IVC procedures. Results indicated that exposure of bovine oocytes to the steroidal glycoalkaloids during in vitro maturation inhibited subsequent pre-implantation embryo development. Potency of the embryo-toxicity varied between these steroidal glycoalkaloids. In Experiment 2, IVM/IVF derived bovine embryos (n=2370) were cultured in vitro in medium supplemented with 6 microM of alpha-solanine, alpha-chaconine, solanidine-N-oxide or IVC medium only. The results showed that the pre-implantation embryo development is inhibited by exposure to these glycoalkaloids. This effect is significant during the later pre-implantation embryo development period as indicated by fewer numbers of expanded and hatched blastocysts produced in the media containing these alkaloids. Therefore, we conclude that in vitro exposure of oocytes and fertilized ova to the steroidal glycoalkaloids from potatoes inhibits pre-implantation embryo development. Furthermore, we suggest that ingestion of Solanum species containing toxic amounts of glycoalkaloids may have negative effects on pre-implantation embryonic survival.

Animals↗

Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering.

Efficacy of aligned poly(l-lactic acid) (PLLA) nano/micro fibrous scaffolds for neural tissue engineering is described and their performance with random PLLA scaffolds is compared as well in this study. Perfectly aligned PLLA fibrous scaffolds were fabricated by an electrospinning technique under optimum condition and the diameter of the electrospun fibers can easily be tailored by adjusting the concentration of polymer solution. As the structure of PLLA scaffold was intended for neural tissue engineering, its suitability was evaluated in vitro using neural stem cells (NSCs) as a model cell line. Cell morphology, differentiation and neurite outgrowth were studied by various microscopic techniques. The results show that the direction of NSC elongation and its neurite outgrowth is parallel to the direction of PLLA fibers for aligned scaffolds. No significant changes were observed on the cell orientation with respect to the fiber diameters. However, the rate of NSC differentiation was higher for PLLA nanofibers than that of micro fibers and it was independent of the fiber alignment. Based on the experimental results, the aligned nanofibrous PLLA scaffold could be used as a potential cell carrier in neural tissue engineering.

Animals↗

Time course of deterioration of rod and cone function in RCS rat and the effects of subretinal cell grafting: a light- and dark-adaptation study.

To examine how rod and cone function are differentially affected during retinal degeneration, and after subretinal cell grafting, we obtained light- and dark-adaptation curves by recording threshold multiunit responses from the superior colliculus of anesthetized rats. Unoperated RCS dystrophic and non-dystrophic rats were used and the effects of subretinal grafting in dystrophic rats of cells known to limit photoreceptor degeneration were examined. The adaptation curves showed that rod function was severely compromised in unoperated dystrophic RCS rats at low luminance levels, even as early as 21 days of age and that cone thresholds became gradually elevated over time. While cell transplantation preserved both rod and cone photoreceptors, rod function did not recover, although further deterioration of cone threshold responses was prevented. This raises concern that measures of outer nuclear layer thickness may not in themselves be an accurate measure of visual capabilities and efficacy of a restoration strategy.

Adaptation, Ocular↗

Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated miniature pig parotid glands.

The treatment of most head and neck cancer patients includes ionizing radiation (IR). Salivary glands in the IR field suffer irreversible damage. Previously, we reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to rat submandibular glands following IR restored salivary flow to near normal levels. It is unclear if this strategy is useful in larger animals. Herein, we evaluated AdhAQP1-mediated gene transfer after parotid gland IR (20 Gy) in the miniature pig. Sixteen weeks following IR, salivation from the targeted gland was decreased by >80%. AdhAQP1 administration resulted in a dose-dependent increase in parotid salivary flow to approximately 80% of pre-IR levels on day 3. A control Ad vector was without significant effect. The effective AdhAQP1 dose was 2.5 x 10(5) pfu/microl infusate, a dose that leads to comparable transgene expression in murine and minipig salivary glands. Three days after Ad vector administration little change was observed in clinical chemistry and hematology values. These findings demonstrate that localized delivery of AdhAQP1 to IR-damaged salivary glands increases salivary secretion, without significant general adverse events, in a large animal model.

Adenoviridae↗

p53 gene mutations are uncommon but p53 is commonly expressed in anaplastic large-cell lymphoma.

Anaplastic large-cell lymphoma (ALCL), as defined in the World Health Organization, is a heterogeneous category in which a subset of cases is associated with the t(2;5)(p23;q35) or variant translocations resulting in overexpression of anaplastic lymphoma kinase (ALK). p53 has not been assessed in currently defined subsets of ALCL tumors. In this study, we assessed ALK+ and ALK- ALCL tumors for p53 gene alterations using PCR, single-strand conformation polymorphism and direct sequencing methods. We also immunohistochemically assessed ALCL tumors for p53 expression. Three of 36 (8%) ALCL tumors (1/14 ALK+, 2/22 ALK-) with adequate DNA showed p53 gene mutations. By contrast, p53 was overexpressed in 36 of 55 (65%) ALCL tumors (16 ALK+, 20 ALK-). p21, a target of p53, was expressed in 15 of 31 (48%) ALCL tumors including seven of 15 (47%) p53-positive tumors. p21 expression in a subset of ALCL suggests the presence of functional p53 protein. Apoptotic rate was significantly higher in p53-positive than p53-negative tumors (mean 2.78 vs 0.91%, P = 0.0003). We conclude that the p53 gene is rarely mutated in ALK+ and ALK- ALCL tumors. Nevertheless, wild-type p53 gene product is commonly overexpressed in ALCL and may be functional in a subset of these tumors.

Adult↗

Developing an innovative cross-cultural strategy to promote HIV/AIDS prevention in different ethnic cultural groups of China.

The HIV and STIs epidemic in China has had a significant impact among China's ethnic minorities. However, the official traditional approach, which has used an anti-epidemic social campaign, has not paid any attention to the diversity of cultural backgrounds of the many ethnic minority groups. This study carried out in Sichuan Province is the first to explore how to use cultural resources for developing an effective strategy for promoting HIV prevention in different cultural groups in China. One hundred and fifty male volunteers drawn from the Yi (50), Tibetan (50) and majority Han (50) cultural groups were assigned to a direct training programme. After training, these participants spread safe sex messages to other contacts who became an indirect peer diffusion group. A third group of 150 male volunteers from the same three cultural groups but from another relatively comparable community acted as controls. Each participant was interviewed before and after the intervention to assess knowledge, attitudes and behavioural intentions regarding HIV/AIDS prevention. The study examined the cultural appropriateness and effectiveness of peer-led health message diffusion in promoting condom use through a traditional oral communication approach from the direct training groups to the indirect intervention groups and broad peer networks within the Yi, Tibetan and Han cultural communities. Key findings showed that the peer-based oral communication strategy was effective for encouraging condom use with casual sexual partners in both the direct training group and the indirect peer diffusion group in all three cultural groups. There was no significant change in any of the comparison groups. Although change in the majority Han cultural group was generally greater than in the ethnic minority groups, the results clearly suggest that the methods can be successfully adopted to promote safe sexual behaviour in different cultural groups of China.

Adolescent↗

Salient closed boundary extraction with ratio contour.

We present ratio contour, a novel graph-based method for extracting salient closed boundaries from noisy images. This method operates on a set of boundary fragments that are produced by edge detection. Boundary extraction identifies a subset of these fragments and connects them sequentially to form a closed boundary with the largest saliency. We encode the Gestalt laws of proximity and continuity in a novel boundary-saliency measure based on the relative gap length and average curvature when connecting fragments to form a closed boundary. This new measure attempts to remove a possible bias toward short boundaries. We present a polynomial-time algorithm for finding the most-salient closed boundary. We also present supplementary preprocessing steps that facilitate the application of ratio contour to real images. We compare ratio contour to two closely related methods for extracting closed boundaries: Elder and Zucker's method based on the shortest-path algorithm and Williams and Thornber's method based on spectral analysis and a strongly-connected-components algorithm. This comparison involves both theoretic analysis and experimental evaluation on both synthesized data and real images.

Algorithms↗

Allogeneic dendritomas induce anti-tumour immunity against metastatic colon cancer.

Colon cancer (CC) is one of the most common malignancies in the Western world. Although surgical resection is the first choice worldwide, at this point an effective approach for the treatment of patients with metastasis and cancer recurrence post-operation has not yet been found. The aim of this study was to investigate the role of the allogeneic dendritomas from fusion of dendritic cells (DC) and metastatic CC cells in the activation of anti-tumour immunity against metastatic CC. Dendritomas were generated by fused allogeneic human peripheral blood DC with metastatic CC cells using 50% polyethylene glycol. The proliferation of the T cells and the toxicity of the cytotoxic T lymphocytes were observed after T cell pulsed with allogeneic dendritomas. The activated ratios of CD4+T helper 1 and CD8+Tc1 cells were about 51.55 and 65.60% after T cells were mixed with fusions for 24 h, which higher than those of controls. The proliferation of T cells were significantly higher than those of control after T cell pulsed with dendritomas (P < 0.01). Significantly, the activated CD8+ T lymphocytes effectively lysed the CC cells. These results demonstrate that allogeneic dendritomas activate T-cell responses against metastatic CC cells.

Cell Fusion↗

Biosynthesis and purification of a hydrophobic peptide from transmembrane domains of G-protein-coupled CB2 receptor.

A major challenge for the structural study of the seven-transmembrane G-protein-coupled receptors is to obtain a sufficient amount of purified protein at the milligram level, which is required for either nuclear magnetic resonance (NMR) spectroscopy or X-ray crystallography. In order to develop a high-yield and cost-effective method, and also to obtain preliminary structural information for the computer modeling of the three-dimensional receptor structural model, a highly hydrophobic peptide from human cannabinoid subtype 2 receptor CB2(65-101), was chosen to develop high-yield membrane protein expression and purification methods. The peptide included the second transmembrane helix with the associated loop regions of the CB2 receptor. It was over-expressed in Escherichia coli, with a modified TrpDelta LE1413 (TrpLE) leading fusion sequence and a nine-histidine tag, and was then separated and purified from the tag in a preparative scale. An experimental protocol for the chemical cleavage of membrane protein fragment was developed using cyanogen bromide to remove the TrpLE tag from the hydrophobic fusion protein. In addition, protein uniformly labeled with isotopic 15N was obtained by expression in 15N-enriched minimum media. The developed and optimized preparation scheme of expression, cleavage, and purification provided a sufficient amount of peptide for NMR structure analysis and other biophysical studies that will be reported elsewhere. The process of fusion protein cleavage following purification was monitored by high-performance liquid chromatography (HPLC) and mass spectrometry (MS), and the final sample was validated by MS and circular dichroism experiments.

Base Sequence↗

Randomized dose-controlled study of topiramate as first-line therapy in epilepsy.

OBJECTIVES: To evaluate the efficacy and tolerability of topiramate as monotherapy, using a dose-controlled study design. MATERIALS AND METHODS: We conducted a multinational, randomized, double-blind trial in adults and children (> or =6 years old) with epilepsy that was not being treated when randomized to 400 or 50 mg/day topiramate as target maintenance dosages. In addition to > or =2 lifetime unprovoked seizures, patients had to have one or two partial-onset seizures or generalized-onset tonic-clonic seizures in the 3-month retrospective baseline. The primary efficacy end point was time to first seizure; a secondary efficacy measure was the seizure-free rate at 6 months and 1 year. Double-blind treatment continued until 6 months after the last patient was randomized. RESULTS: Kaplan-Meier survival analyses for time to first seizure (intent-to-treat, n = 470) favored 400 mg/day over 50 mg/day (P = 0.0002) as a target maintenance dosage. The first evaluation point with a significant difference (P = 0.046) favoring the higher dose was at day 14 when patients were receiving 100 or 25 mg/day. The probability of being seizure-free at 6 months was 83% in patients randomized to 400 mg/day and 71% in those randomized to 50 mg/day (P = 0.005). Seizure-free rates at 12 months were 76% and 59%, respectively (P = 0.001). Differences favoring the higher dose were significant in patients with partial-onset seizures (P = 0.009) and in those with generalized-onset tonic-clonic seizures (P = 0.005). The most common dose-related adverse events were paresthesia, weight loss, and decreased appetite. Discontinuations due to cognitive-related adverse events were 2% in the 50-mg group and 7% in the 400-mg group. Overall, 7% and 19%, respectively, discontinued with adverse events during the median treatment duration of 9 months. CONCLUSION: Topiramate is effective as monotherapy in adults and children. Because a therapeutic effect emerges during titration, clinicians should adjust dosages in step-wise fashion with intermediate stopping points, e.g., 100 mg/day, to evaluate patient response and achieve the optimal maintenance dosage.

Adolescent↗

Sustained and stable hematopoietic donor-recipient mixed chimerism after unrelated cord blood transplantation for adult patients with severe aplastic anemia.

We evaluated the engraftment of donor cells from unrelated cord blood into adult patients with severe aplastic anemia (SAA) and the outcome of allo-CBSCT (cord blood stem cell transplantation). Nine patients were conditioned with decreased dosage of immunosuppressive agents of CTX (60 mg/kg) and ALG (120 mg/kg). The prophylaxis of GVHD consisted of standard CsA and MTX. Patients have a media age of 25.3 yr (range: 15-37), and a median weight of 57.2 kg (range: 52.5-60) at the time of transplantation. Cord blood searches were all conducted at Guangzhou Cord Blood Bank. The engraftment state of the donor cells into recipients was confirmed by microsatellite DNA fingerprinting and fluorescent quantitative PCR analysis. Engrafted evidence has been found in seven patients involved by biomolecular analyses showing donor-recipient mixed chimerism post-transplant which was stable and persistent. After a median follow up of 32.2 months (range: 4-69), seven patients were alive and disease free. This study shows that durable donor-recipient stable mixed chimerism can be achieved by unrelated CBSCT in patients with SAA. Umbilical cord blood could be employed as a source of hematopoietic stem cell for adult transplantation.

Adolescent↗

Ability of new APTIMA CT and APTIMA GC assays to detect Chlamydia trachomatis and Neisseria gonorrhoeae in male urine and urethral swabs.

A clinical evaluation was conducted in six North American centers to determine the ability of APTIMA CT (ACT) and APTIMA GC (AGC) nucleic acid amplification assays to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections in 1,322 men by testing their urethral swabs and first-catch urine (FCU). The results obtained with ACT and AGC assays were compared to an infected patient status determined by testing the specimens with the APTIMA Combo 2 and the BD ProbeTec energy transfer multiplex assays. Symptoms did not influence the values. Positive and negative agreements of the ACT and AGC assays for individual specimens were high, with each comparator assay ranging between 94.3 and 100% for positives and 93.9 and 99.4% for negatives. The ACT and AGC assays performed on noninvasive specimens such as FCU effectively identified C. trachomatis or N. gonorrhoeae infections in symptomatic and asymptomatic men and should be suitable for screening male populations.

Adolescent↗

Fuzzy control of nitrogen removal in predenitrification process using ORP.

In order to meet increasingly stringent discharge standards, new applications and control strategies for the sustainable removal of nitrogen from wastewater have to be implemented. In the past years, numerous studies have been carried out dealing with the application of fuzzy logic to improve the control of the activated sludge process. In this paper, fuzzy control strategies of predenitrification systems are presented that could lead to better effluent quality and, in parallel, to a reduction of chemicals consumption. Extensive experimental investigations on lab scale plant studies have shown that there was excellent correlation between nitrate concentration and ORP value at the end of the anoxic zone. Results indicated that ORP could be used as an on-line fuzzy control parameter of nitrate recirculation and external carbon addition. The optimal value of ORP to control nitrate recirculation and external carbon addition was - 86 +/- 2 mV and - 90 +/- 2 mV, respectively. The results obtained with real wastewater also showed the good performance and stability of the fuzzy controllers independently from external disturbances. The integrated control structure of nitrate recirculation and external carbon addition in the predenitrification system is also presented.

Bioreactors↗