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Biomedical subjects

Tao Zhang

Publications and source records attributed to Tao Zhang.

At least 37 records · Page 2Linked to original sources
PubMed2006

Association of human serum apolipoprotein A5 with lipid profiles affected by gender.

BACKGROUND: Apolipoprotein A5 (ApoA5) is present in human serum at a very low concentration. We developed a new method to determine ApoA5 concentration in human serum, and to investigate the correlation between serum ApoA5 and the lipid profiles in healthy subjects, and to analyze whether the correlation was affected by gender. METHODS: All the subjects (total 92, male 50, female 42) were healthy subjects without any medication. Lipids were measured enzymatically. An ELISA performed by a couple of monoclonal antibodies was used to measure serum ApoA5. RESULTS: The average ApoA5 concentration was 182.7+/-104.7 ng/ml ranging from 5.4 to 455.6 ng/ml. Serum ApoA5 concentration was negatively correlated with TG in female (r=-0.496, P=0.001). In all subjects, ApoA5 concentration was positively correlated to HDL-C (r=0.453, P<0.001). This correlation was more predominant in female (r=0.617, P<0.001) than in male (r=0.289, P=0.042). ApoA5 concentration was negatively correlated to body mass index (BMI) with more significance in female than in male (r=-0.345, P=0.001 for all; r=-0.456, P=0.002 for female; r=-0.198, P=0.167 for male). CONCLUSIONS: The serum concentration of ApoA5 was very low. The concentration of ApoA5 was negatively correlated with TG and BMI, but positively correlated with HDL-C. The correlations were affected by gender.

Adult↗
PubMed2006

SUMO-1 modification increases human SOD1 stability and aggregation.

The mutations in the gene encoding copper-zinc superoxide dismutase (SOD1) cause approximately 20% cases of familial amyotrophic lateral sclerosis (FALS), characterized by selective loss of motor neurons. Mutant SOD1 forms inclusions in tissues from FALS patients. However, the precise mechanism of the accumulation of mutant SOD1 remains unclear. Here we show that human SOD1 is a substrate modified by SUMO-1. A conversion of lysine 75 to an arginine within a SUMO consensus sequence in SOD1 completely abolishes SOD1 sumoylation. We further show that SUMO-1 modification, on both wild-type and mutant SOD1, increases SOD1 steady state level and aggregation. Moreover, SUMO-1 co-localizes onto the aggregates formed by SOD1. These findings imply that SUMO-1 modification on lysine 75 may participate in regulating SOD1 stability and its aggregation process. Thus, our results suggest that sumoylation of SOD1 may be involved in the pathogenesis of FALS associated with mutant SOD1.

Cell Line↗
PubMed2006

Long-term studies on the stability and oral bioavailability of cyclosporine A nanoparticle colloid.

The present study was geared at the long-term stability and the changes in oral bioavailability of CyA Eudragit S100 nanoparticles stabilized by suspending agents. CyA Eudragit S100 nanoparticle colloids were prepared by quasi-emulsion solvent diffusion technique and they were mixed with Xanthan gum to obtain suspended nanoparticle colloids. The suspended nanoparticle colloids were preserved at different temperatures for different period of time, as long as 18 months. During the storage period, the CyA concentration, particle size, pH and viscosity were determined. The results indicated that CyA concentration, particle size and viscosity of the colloids had no obvious change. However, the pH increased slightly from 5.5 to about 6.4. The results of bioavailability and pharmacokinetic study revealed that all formulations of nanoparticles showed higher C(max) and higher AUC(0-24) values than that of reference (Neoral). The relative bioavailability of S-CyA-S100 NP initial compared with Neoral was 162.8%. The C(max) and AUC(0-24) values of nanoparticle formulations at 12 and 18 months were both lower than that of the initial. The bioequivalency was suggested between the tested nanoparticle formulations at the initial and 12 months. It was deduced by surface analysis, TEM observation, in vitro release as well as the characteristics of Eudragit S100 that the decrease in bioavailability might be due to the pH change of the nanoparticle colloid.

Administration, Oral↗
PubMed2006

A new approach for the asymmetric total synthesis of umbelactone.

The asymmetric total syntheses of (R)-(+)- and (S)-(-)-umbelactone were achieved by using the Sharpless asymmetric epoxidation reaction to generate the stereogenic center and a ring-closing metathesis (RCM) for the formation of the lactone structure. Starting from 3-methyl-2-buten-1-ol, the asymmetric total synthesis was achieved in an efficient 6-step protocol with an overall yield of 16%.

Catalysis↗
PubMed2006

Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial.

PURPOSE: To evaluate the effectiveness of patient-controlled methylphenidate as compared with placebo in cancer patients with fatigue, as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F). PATIENTS AND METHODS: Patients with a fatigue score of at least 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) and hemoglobin level of at least 10 g/dL were included. Patients were randomly assigned to receive 5 mg methylphenidate or placebo every 2 hours as needed (maximum of four capsules a day), for 7 days. Patients completed a daily diary including study drug record and fatigue intensity. A research nurse telephoned patients daily to assess toxicity and fatigue level. All patients were offered open-label methylphenidate for 4 weeks. FACIT-F and the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 15, and 36. The FACIT-F fatigue subscore on day 8 was considered the primary end point. RESULTS: Of 112 patients randomly assigned, 52 patients in the methylphenidate and 53 in the placebo group were assessable for analysis. Fatigue intensity improved significantly on day 8 in both the methylphenidate and placebo groups. However, there was no significant difference in fatigue improvement by FACIT-F (P = .31) or ESAS (P = .14) between groups. In open-label phase, fatigue intensity maintained low as compared with baseline. No significant toxicities were observed. CONCLUSION: Both methylphenidate and placebo resulted in significant symptom improvement. Methylphenidate was not significantly superior to placebo after 1 week of treatment. Longer study duration is justified. The role of daily telephone calls from a research nurse should be explored as a palliative care intervention.

Adult↗
PubMed2006

Nicotine prevents the apoptosis induced by menadione in human lung cancer cells.

Approximately 50% of long-term cigarette smokers die prematurely from the adverse effects of smoking, including on lung cancer and other illnesses. Nicotine is a main component in tobacco and has been implicated as a potential factor in the pathogenesis of human lung cancer. However, the mechanism of nicotine action in the development of lung cancer remains largely unknown. In the present study, we designed a nicotine-apoptosis system, by pre-treatment of nicotine making lung cancer cell A549 to be in a physiological nicotine environment, and observed that nicotine promoted cell proliferation and prevented the menadione-induced apoptosis, and exerts its role of anti-apoptosis by shift of apoptotic stage induced by menadione from late apoptotic stage to early apoptotic stage, in which NF-kappaB was up-regulated. Interference analysis of NF-kappaB in A549 cells showed that knock down of NF-kappaB resulted in apoptosis promotion and counteracted the protective effect of nicotine. The findings suggest that nicotine has potential effect in lung cancer genesis, especially in patients with undetectable early tumor development and development of specific NF-kappaB inhibitors would represent a potentially exciting new pharmacotherapy for tobacco-related lung cancer.

Apoptosis↗
PubMed2006

Deficiency of centromere-associated protein Slk19 causes premature nuclear migration and loss of centromeric elasticity.

The cohesin complex prevents premature segregation of duplicated chromosomes by providing resistance to the pole-ward pull by spindle microtubules. The centromeric region (or sister kinetochores) bears the majority of this force and undergoes transient separation prior to anaphase, indicative of its elastic nature. A cysteine protease, separase, cleaves the cohesin subunit Scc1 and dissolves cohesion between sister chromatids, initiating their separation. Separase also cleaves the kinetochore protein Slk19 during anaphase. Slk19 has been implicated in stabilization of the mitotic spindle and regulation of mitotic exit, but it is not known what role it plays at the kinetochores. We show that during pre-anaphase arrest, the spindle in slk19Delta cells is excessively dynamic and the nuclei move into mother-daughter junction prematurely. As a result, the chromatin mass undergoes partial division that requires neither anaphase promoting complex (APC) activity nor Scc1 cleavage. Partial division of the chromatin mass is accompanied by the loss of the centromeric region's ability to resist pole-ward pull by the spindle. Slk19 physically associates with Scc1 and this association appears necessary for efficient cleavage of Slk19 by separase. Our results suggest that Slk19 participates in regulating nuclear migration and, in conjunction with cohesin complex, may be involved in the maintenance of centromeric tensile strength to resist the pole-ward pull.

Cell Cycle Proteins↗
PubMed2006

[Effects of gastrin receptor antagonist and cyclooxygenase-2 inhibitor on proliferation and apoptosis of gastric cancer cell].

OBJECTIVE: To investigate the regulative roles of the gastrin receptor antagonist proglumide and the specific cyclooxygenase (COX)-2 inhibitor NS-398 on the proliferation and apoptosis of gastric cancer cells. METHODS: Human gastric cancer cells of the line MKN-45 were routinely cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum. Subconfluent cell cultures were treated with proglumide at a final concentration of 5 mmol/L, NS-398 at a final concentration of 10.0 micromol/L, or proglumide in combination with NS-398 for 48 h. The growth and proliferation of MKN-45 cells were analyzed with MTT assay. Flow cytometric analysis was used to detect the apoptosis of the gastric cancer cells. RT-PCR and Western blotting were used to detect the expression of apoptosis-inhibited gene bcl-2 mRNA and protein. RESULTS: The apoptosis rates of the cells treated by proglumide, NS-398, and combination of two agents were 24.7% +/- 3.2%, 26.7% +/- 3.4%, and 36.1% +/- 4.6% respectively, all significantly higher than that in the control group (1.6% +/- 0.6%, all P < 0.01). The apoptosis rates of the MKN-45 cells treated with proglumide combined with NS-398 was significantly greater than those of the cells treated by the two agents alone (both P < 0.05). Treatment with proglumide and NS-398 significantly reduced the bcl-2 mRNA and protein expression in the MKN-45 cells (P < 0.05). CONCLUSION: Both proglumide and NS-398 inhibit the proliferation and induce the apoptosis of human gastric cells. This apoptosis may be mediated by down-regulation of the expression of apoptosis-inhibited gene bcl-2. Co-treatment with proglumide and NS-398 have synergistic anticancer role.

Apoptosis↗
PubMed2006

OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models.

OSI-930 is a novel inhibitor of the receptor tyrosine kinases Kit and kinase insert domain receptor (KDR), which is currently being evaluated in clinical studies. OSI-930 selectively inhibits Kit and KDR with similar potency in intact cells and also inhibits these targets in vivo following oral dosing. We have investigated the relationships between the potency observed in cell-based assays in vitro, the plasma exposure levels achieved following oral dosing, the time course of target inhibition in vivo, and antitumor activity of OSI-930 in tumor xenograft models. In the mutant Kit-expressing HMC-1 xenograft model, prolonged inhibition of Kit was achieved at oral doses between 10 and 50 mg/kg and this dose range was associated with antitumor activity. Similarly, prolonged inhibition of wild-type Kit in the NCI-H526 xenograft model was observed at oral doses of 100 to 200 mg/kg, which was the dose level associated with significant antitumor activity in this model as well as in the majority of other xenograft models tested. The data suggest that antitumor activity of OSI-930 in mouse xenograft models is observed at dose levels that maintain a significant level of inhibition of the molecular targets of OSI-930 for a prolonged period. Furthermore, pharmacokinetic evaluation of the plasma exposure levels of OSI-930 at these effective dose levels provides an estimate of the target plasma concentrations that may be required to achieve prolonged inhibition of Kit and KDR in humans and which would therefore be expected to yield a therapeutic benefit in future clinical evaluations of OSI-930.

Administration, Oral↗
PubMed2006

[Mean flow of saphenous vein graft and its influencing factors in patients performed coronary artery bypass grafting].

OBJECTIVE: To analyze the mean blood flow of saphenous vein (SV) graft and it's influencing factors in off-pump coronary artery bypass grafting by using transit-time flowmeter (TTFM). METHODS: Three hundred and twenty-six patients were studied. After all anastomoses were completed, and hemo-dynamic status was stable, TTFM was utilized to measure and record the SV flow wave, pulsatility index (PI), value of mean flow, diastolic and systolic peak flow, vascular resistance, insufficiency ratio and mean blood pressure. The standard conditions of good graft status to define the normal mean flow included good diastolic augmentation of blood wave, PI less than 5, intraoperative and postoperative no significant change in electrocardiogram, and smoothly postoperative recovery. RESULTS: Total mean flow calculated from that of all patients was (39 +/- 23) ml/min (10-153 ml/min). Majority mean value (60.1%, 196/326) was in the range of 20-50 ml/min. Statistics showed that mean flow was significantly related to vascular resistance and diastolic peak flow and PI rather than the other factors (r was -0.95, 0.77 and -0.51 respectively). CONCLUSIONS: For the patients, over 15 ml/min mean flow of SV graft is acceptable, and over 35 ml/min is satisfactory. The diastolic peak flow and vascular resistance are two important factors influencing mean flow.

Adult↗
PubMed2006

A global map of p53 transcription-factor binding sites in the human genome.

The ability to derive a whole-genome map of transcription-factor binding sites (TFBS) is crucial for elucidating gene regulatory networks. Herein, we describe a robust approach that couples chromatin immunoprecipitation (ChIP) with the paired-end ditag (PET) sequencing strategy for unbiased and precise global localization of TFBS. We have applied this strategy to map p53 targets in the human genome. From a saturated sampling of over half a million PET sequences, we characterized 65,572 unique p53 ChIP DNA fragments and established overlapping PET clusters as a readout to define p53 binding loci with remarkable specificity. Based on this information, we refined the consensus p53 binding motif, identified at least 542 binding loci with high confidence, discovered 98 previously unidentified p53 target genes that were implicated in novel aspects of p53 functions, and showed their clinical relevance to p53-dependent tumorigenesis in primary cancer samples.

Binding Sites↗
PubMed2006

Enhancement of myoblast microencapsulation for gene therapy.

One method of nonviral-based gene therapy is to implant microencapsulated nonautologous cells genetically engineered to secrete the desired gene products. Encapsulating the cells within a biocompatible permselective hydrogel, such as alginate-poly-L-lysine-alginate (APA), protects the foreign cells from the host immune system while allowing diffusion of nutrients and the therapeutic gene products. An important consideration is which kind of cells is the best candidate for long-term implantation. Our previous work has shown that proliferation and differentiation of encapsulated C2C12 myoblasts in vitro are significantly improved by inclusion of basic fibroblast growth factor (bFGF), insulin growth factor II (IGF-II), and collagen within the microcapsules ("enhanced" capsules). However, the effects of such inclusions on the functional status of the microcapsules in vivo are unknown. Here we found that comparing the standard with the enhanced APA microcapsules; there was no difference in the rates of diffusion of recombinant products of different sizes, that is, human factor IX (FIX, 65 kDa), murine IgG (150 kDa), and a lysosomal enzyme, beta-glucuronidase (300 kDa), thus providing a key requirement of such an immunoprotective device. Furthermore, the creatine phosphokinase activity and myosin heavy chain staining (markers for differentiation of the myoblasts) and the cell number per capsule in the enhanced microcapsules indicated a higher degree of differentiation and proliferation when compared to the standard microcapsules, thus demonstrating an improved microenvironment for the encapsulated cells. Efficacy was tested in a melanoma cancer tumor model by treating tumor induced by B16-F0/neu tumor cells in mice with myoblasts secreting angiostatin from either the standard or enhanced APA microcapsules. Mice treated with enhanced APA-microcapsules had an 80% reduction in tumor volume at day 21 compared to a 70% reduction in those treated with standard APA-microcapsules. In conclusion, enhancement of APA microcapsules with growth factors and collagen did not adversely affect their permeability property and therapeutic efficacy. However, the enhanced differentiation and viability of the encapsulated myoblasts in vivo should be advantageous for long-term delivery with this method of gene therapy.

Angiotensins↗
PubMed2006

TGF-betal transgenic mouse model of thoracic irradiation: modulation of MMP-2 and MMP-9 in the lung tissue.

To investigate the effects of TGF-beta1 on the two gelatinases (MMP-2 and MMP-9), and their roles in lung remodeling after irradiation-induced lung injury. Expressions of TGF-beta1 were measured with western blot, and expressions of MMP-2 and MMP-9 were analyzed with zymography in a -TGF-beta1 transgenic mouse model after thoracic irradiation with 12 Gy. We found expressions of TGF-beta1 in the lung from the transgenic mice were three folds as compared to those from control mice. With densitometrical analysis, we found a significant decrease in MMP-9 activity in lung homogenates from the transgenic mice as compared with those from non-transgenic control mice 8 weeks after sham-irradiation (relative MMP-9 activity: C: 1.000 0.1091; TG: 0.4772 +/- 0.470 (n = 8, P < 0.05). But MMP-2 was constitutively expressed in the lung homogenates from the transgenic mice as compared to those from control mice 8 weeks after sham-irradiation (relative MMP-2 activity 8 weeks after sham-irradiation: C: 1.000 +/- 0.1556, TG: 1.0075 +/- 0.1472). Eight weeks after thoracic irradiation with 12 Gy, we observed a significant increase of MMP-2 and MMP-9 activity in lung homogenates from both transgenic and normal mice. In TGF-beta1 transgenic mice relative MMP-9 activity was increased to 1.5321 +/- 0.2217 folds 8 weeks after thoracic irradiation with 12 Gy as compared to those after sham-irradiation (1.000 +/- 0.2153), and relative MMP-2 activity was increased to 1.7142 +/- 0.4231 folds. Our results show that TGF-beta1 itself down-regulates activity of MMP-9, thereby decreases ECM degradation in lungs of TGF-beta1 transgenic mice. Also we find that ionizing irradiation upregulates both MMP-2 and MMP-9 activity. Over-expressions of MMP-9 and MMP-2 after lung irradiation are involved in the inflammatory response associated with radiation-induced lung injury, and maybe further in radiation-induced lung fibrosis.

Animals↗
PubMed2006

Genetic analysis and gene mapping of purple stigma in rice.

A new double-haploid (rdh) rice plant with purple stigma and red seeds was discovered by tissue culture. Genetic analysis suggested that the trait of rdh purple stigma was controlled by a pair of dominant gene. Polymorphic analysis of microsatellite markers demonstrated that the purple stigma gene of rdh was located on rice chromosome 6 at 4.2 cM, 0.35 cM and 0.53 cM from microsatellite markers RM276, RM253 and RM111, respectively. It was believed that the purple stigma gene of rdh was the first mapped purple stigma gene on rice chromosome 6. This purple stigma gene was designated tentatively as Ps-4.

Chromosome Mapping↗
PubMed2006

Errors in symptom intensity self-assessment by patients receiving outpatient palliative care.

BACKGROUND: Patient-based symptom scores are the standard method for assessment in palliative care. There has been limited research on the frequency of errors upon using this approach. The Edmonton Symptom Assessment Scale (ESAS) is a reliable and valid assessment tool routinely used for symptom intensity assessment in our cancer center. OBJECTIVE: To determine if patients were scoring the symptoms on the ESAS in the way it was supposed to be scored. SETTINGS: The study was carried out at the outpatient palliative care center. DESIGN AND SUBJECTS: Retrospective review of 60 consecutive patient charts was done where the patient had initially scored the ESAS. The physician looked at this scoring on the ESAS and went back to the patient to do the scoring again to see if the patient had scored it in the way it was intended to be scored. The same physician did the assessment on all of the patients. OUTCOME MEASURES: Level of agreement (weighted kappa) before versus after the physician visit; Screening performance of patient completed ESAS for mild and moderate symptom intensity. RESULTS: Complete agreement ranged from 58% (sleep) to 82% (well-being); the weighted kappa ranged from 0.49 (drowsiness) to 0.78 (well-being). There was more agreement for symptoms such as dyspnea, nausea, anxiety, and depression and less agreement for symptoms such as lack of sleep and lack of appetite. The screening performance of the initial patient self assessment showed less sensitivity for nausea, drowsiness if the intensity was mild and less sensitivity for pain, nausea, anxiety, and drowsiness if the intensity was moderate. CONCLUSIONS: Vigilance needs to be maintained about the ESAS scores done by the patients particularly for symptoms of sleep, appetite, and pain. There is a likelihood of error if doctors or nurses do not routinely check the way patients have completed the assessment form. More research is needed to determine the best way to teach patients how to minimize errors in self-reporting of symptoms.

Adult↗
PubMed2006

The Edmonton Symptom Assessment System as a screening tool for depression and anxiety.

PURPOSE: Mood disorders are among the most important psychiatric problems in patients with cancer. However, they are frequently underdiagnosed and therefore undertreated. This may lead to difficulties with symptom control, social withdrawal, and poor quality of life. This study was conducted to evaluate the screening performance of the Edmonton Symptom Assessment System (ESAS) for depression and anxiety, compared to Hospital Anxiety and Depression Scale (HADS). METHODS: We retrospectively reviewed and analyzed ESAS and HADS data collected from three previous clinical trials conducted by our group. The diagnosis of depression and/or anxiety, and moderate/severe depression and/or anxiety made when patients scored 8 or more, and 11 or more in HADS questionnaire, respectively. The sensitivity, specificity, positive, and negative predictive values for ESAS were calculated. RESULTS: Of 216 patients analyzed, the median (range) score for depression was 2 (0-10) and anxiety 3 (0-10) using ESAS, and 6 (0-16) and 7 (0-19) using HADS, respectively. A cut off of 2 out of 10 or more in the ESAS gave a sensitivity of 77% and 83% with a specificity of 55% and 47% for depression and moderate/severe depression, respectively. A cutoff of 2 out of 10 or more in the ESAS gave a sensitivity of 86% and 97%, and a specificity of 56% and 43% for anxiety and moderate/severe anxiety, respectively. CONCLUSION: Our data suggest that the ideal cutoff point of ESAS for the screening of depression and anxiety in palliative care is 2 out of 10 or more. More research is needed to define the ideal cutoff point for screening of severe depression and anxiety.

Adult↗
PubMed2006

Neural network-based hybrid human-in-the-loop control for meal assistance orthosis.

In order to assist some elderly and disabled people, who have partly or completely lost the ability of moving their upper limbs due to neurological disabilities or spinal cord disease, to take meals by themselves independently, a new type of meal assistance orthosis was recently developed. This paper presents a neural network-based hybrid human-in-the-loop control for this meal assistance orthosis with functional and safety purposes. In this approach, the position control and the force-free control are integrated into a single controller based on the model of meal assistance orthosis. By means of the position control, the meal assistance orthosis is controlled to generate appropriate compensation forces for assisting the movement of upper limb. In order to reduce the risk of hurting the bodies of human end-users and of damaging the device due to the impact from large external forces, with the force-free control, the meal assistance orthosis can flexibly move with the driven of large external forces. In addition, the controller of the meal assistance orthosis can be smoothly switched between the position control and the force-free control through a designed process to avoid instantaneously generating large external force owing to hard switching. In order to improve the adaptability of the proposed approach to different subjects, neural networks are adopted in the controller. Moreover, the proposed approach fully takes into account the influence of external forces induced by upper limb in the control process to form a kind of human-in-the-loop control. With the simulation and experiment of the meal assistance orthosis, the effectiveness of the proposed method was verified.

Algorithms↗