Biomedical subjects

Lei Zhang

Publications and source records attributed to Lei Zhang.

At least 217 records · Page 12Linked to original sources

PubMed2005

Proteomic analysis of hepatitis B virus-associated hepatocellular carcinoma: Identification of potential tumor markers.

Hepatocellular carcinoma (HCC) is a malignancy of both underdeveloped and developing countries. Proteomes of ten pairs of clinical hepatitis B virus associated HCC tissue samples were obtained by high resolution two-dimensional gel electrophoresis. Comprehensive analyses of proteins associated with B-type HCC were focused on total differentially expressed proteins (> or = two-fold increase or decrease, Student's t-test, p < 0.05) from one pair of samples. Protein identification was done by peptide mass fingerprinting with matrix assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography-tandem mass spectrometry. Comparative analyses of proteins associated with B-type HCC included repeat statistics in ten cases. A total of 100 protein spots, corresponding to 80 different gene products, were identified. Proteins whose expression levels were different by more than 2-fold in at least 50% of the cases (five of ten cases) were further analyzed and 45 proteins were selected out as candidates for HCC-associated proteins. Western blotting further validated up-regulated expressions of two candidate proteins in tumor tissues: proliferating cell antigen and stathmin 1. This comprehensive and comparative analyses of proteins associated with B-type HCC could provide useful molecular markers for diagnostics and prognostics and for therapeutic targets. The physiological significance of the differential expressions for several candidate proteins are discussed.

Adult↗

PubMed2005

Large-scale identification of human biliary proteins from a cholesterol stone patient using a proteomic approach.

Gallbladder bile, one of the most important body fluids, is composed of water, inorganic ions, conjugated bile salts, phospholipids, cholesterol, bilirubin, mucin and proteins. The separation and identification of bile proteins remain difficult due to the complexity of this matrix. In the present study, human gallbladder bile was obtained from a cholesterol stone patient, and the proteins were isolated and purified by dialysis, precipitation and delipidation procedures. The resulting proteins were divided into several aliquots. One aliquot was subjected to two-dimensional gel electrophoresis (2DE). The protein spots were then in-gel digested and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). Another aliquot was directly digested and analyzed by a combination of strong cation-exchange (SCX) and reversed-phase (RP) chromatography prior to tandem mass spectrometry (2D-LC/MS/MS). Eventually, 48 and 218 unique proteins were identified from 2DE/MS and 2D-LC/MS/MS, respectively, resulting in a total of 222 unique identified proteins. Of the 218 proteins identified by 2D-LC/MS/MS, 92 were identified based on more than one unique tryptic peptide, and, of the total 222 proteins, 98 were identified based on more than one unique tryptic peptide.

Aged↗

PubMed2005

Exploiting temporal information in functional magnetic resonance imaging brain data.

Functional Magnetic Resonance Imaging(fMRI) has enabled scientists to look into the active human brain, leading to a flood of new data, thus encouraging the development of new data analysis methods. In this paper, we contribute a comprehensive framework for spatial and temporal exploration of fMRI data, and apply it to a challenging case study: separating drug addicted subjects from healthy non-drug-using controls. To our knowledge, this is the first time that learning on fMRI data is performed explicitly on temporal information for classification in such applications. Experimental results demonstrate that, by selecting discriminative features, group classification can be successfully performed on our case study although training data are exceptionally high dimensional, sparse and noisy fMRI sequences. The classification performance can be significantly improved by incorporating temporal information into machine learning. Both statistical and neuroscientific validation of the method's generalization ability are provided. We demonstrate that incorporation of computer science principles into functional neuroimaging clinical studies, facilitates deduction about the behavioral probes from the brain activation data, thus providing a valid tool that incorporates objective brain imaging data into clinical classification of psychopathologies and identification of genetic vulnerabilities.

Algorithms↗

PubMed2005

Microspheres of corn protein, zein, for an ivermectin drug delivery system.

A novel microsphere drug delivery system of ivermectin (IVM) using hydrophobic protein zein was prepared by the phase separation method and characterized by a scanning electron microscope and laser light scattering particle size analyzer. Releases of model drug IVM from zein microspheres, tabletted microspheres and pepsin degradation of tabletted microspheres were also performed in vitro to investigate the mechanism of model drug release. The results show that the zein microspheres and tabletted microspheres are suitable for use as a sustained-release form of IVM. The microspheres may also be useful in drug targeting system since the diameter of the microspheres is appropriate for phagocytosis by macrophages. Moreover, the release of IVM from enzymatic degraded tabletted microspheres shows a zero-order release, implying a potential application in tissue engineering for preparing scaffold, which is composed of microspheres encapsulating bioactive components for stimulating cell differentiation and proliferation.

Coated Materials, Biocompatible↗

PubMed2005

Functional MRI in attention-deficit hyperactivity disorder: evidence for hypofrontality.

Using event-related functional magnetic resonance imaging to study the Stroop effect on both behavioral and brain activation of ADHD children off or on methylphenidate (MPH). Nine ADHD boys (aged 9.8-14.5 years) and 9 age-matched normal controls were included. A Stroop-like paradigm was used. AFNI (Analysis of Functional NeuroImaging) and its Deconvolution Analysis were used in a descriptive comparison between ADHD and control groups. (1) Both behavioral reaction time and brain activation showed Stroop effect in controls but neither was found in ADHD children off MPH. When MPH was administered, the Stroop effect tended to appear. (2) The activation volume (AV) of prefrontal cortex (PFC) in both the neutral (NC) and interference conditions (IC) in ADHD children off MPH was smaller than in controls. AV of anterior cingulate cortex in the IC in ADHD children off MPH was smaller than that in controls, but was similar in the NC to that in controls. AV of the basal ganglia, insula and cerebellum was also smaller in the IC, but was larger in the NC for ADHD children off MPH compared with controls. These findings are consistent with prior findings of hypofrontality in ADHD children and implicate a compensatory network including basal ganglia, insula and cerebellum for relative lower cognitive load tasks.

Adolescent↗

PubMed2005

Phosphorylation by double-time/CKIepsilon and CKIalpha targets cubitus interruptus for Slimb/beta-TRCP-mediated proteolytic processing.

Hedgehog (Hh) proteins govern animal development by regulating the Gli/Ci family of transcription factors. In Drosophila, Hh signaling blocks proteolytic processing of full-length Ci to generate a truncated repressor form. Ci processing requires sequential phosphorylation by PKA, GSK3, and a casein kinase I (CKI) family member(s). Here we show that Double-time (DBT)/CKIepsilon and CKIalpha act in conjunction to promote Ci processing. CKI phosphorylates Ci at three clusters of serine residues primed by PKA and GSK3 phosphorylation. CKI phosphorylation of Ci confers binding to the F-box protein Slimb/beta-TRCP, the substrate recognition component of the SCF(Slimb/beta-TRCP) ubiquitin ligase required for Ci processing. CKI phosphorylation sites act cooperatively to promote Ci processing in vivo. Substitution of Ci phosphorylation clusters with a canonical Slimb/beta-TRCP recognition motif in beta-catenin renders Slimb/beta-TRCP binding and Ci processing independent of CKI. We propose that phosphorylation of Ci by CKI creates multiple Slimb/beta-TRCP binding sites that act cooperatively to recruit SCF(Slimb/beta-TRCP).

Amino Acid Sequence↗

PubMed2005

An effective and simple expansion system for megakaryocyte progenitor cells using a combination of heparin with thrombopoietin and interleukin-11.

Transfusion of ex vivo expanded megakaryocyte (MK) progenitor cells has been suggested to shorten the time of platelet recovery in the thrombocytopenia induced by radiotherapy or chemotherapy. Here, we report an effective and simple expansion system of MK progenitor cells from cord blood (CB) CD34(+) cells using a combination of thrombopoietin (TPO), interleukin (IL)-11, and heparin. When the CB CD34(+) cells were cultured in a liquid expansion system in the presence of TPO + recombination human (rh)IL-11 + heparin for 7 days, the number of CB CD34(+)/CD41a(+) cells was significantly increased compared to control groups (p < 0.05). When the suspension cells collected from 7-day liquid culture were replated in semisolid cultures, increased large MK colonies were observed in the culture with combination of TPO + IL-11 + heparin compared to those of control groups. In vivo, transfusion of CD34(+) cells expanded with TPO + IL-11 + heparin into irradiated nonobese diabetic/severe combined immunodeficient mice significantly accelerated platelet recovery. These data indicate that heparin as effective cofactor for TPO and IL-11 promotes expansion of MK progenitor cells from CB CD34(+) cells. This expansion system is simple and effective and could be used for the treatment of thrombocytopenia after radiotherapy or chemotherapy.

Animals↗

PubMed2005

Size-fractionated thorium isotopes (228Th, 230Th, 232Th) in surface waters in the Jiulong River estuary, China.

Thorium isotopes (228Th, 230Th, 232Th and 234Th) are useful tracers for studying particle dynamics and trace element scavenging in marine environments. In this study, surface waters were collected along a salinity gradient from the Jiulong River estuary, China, for determination of activity concentrations of 228Th, 230Th and 232Th in different size fractions, namely, the >53 microm, 10-53 microm, 2-10 microm, 0.4-2 microm, 10 kDa-0.4 microm and the <10 kDa fractions. Our results indicated that the activity concentrations of 228Th, 230Th and 232Th in the Jiulong River estuarine waters were significantly higher than most of the previously reported values in coastal and oceanic seawaters, suggesting a higher lithogenic U and Th contribution from the Jiulong River Basin. When normalized to the particulate mass concentration, the activity concentrations of the three thorium isotopes decreased with increasing particle size, demonstrating the important role of surface areas of particles in controlling the scavenging of thorium from the water column. The partitioning of three thorium isotopes showed a common characteristic, i.e., the >53 microm fraction had the least share (0-1%), while the 10-53 microm fraction had the largest share of Th isotopes. The average value of the 230Th/232Th activity ratio (230Th/232Th)(A.R.) increased from 0.8 in the >53 microm fraction to 3.7 in the 10 kDa-0.4 microm fraction, indicating that the radiogenic Th isotopes are preferentially scavenged by the small size particles. (230Th/232Th)(A.R.) in the <10 kDa and 10 kDa-0.4 microm fractions were similar, however, suggesting a similar chemical composition and/or equilibrium partitioning between the low molecular weight and colloidal Th. It was very interesting to note that the geochemical behaviors of the three Th isotopes were different from each other. Dissolved 228Th had the highest concentration in the mid-salinity region, showing a non-conservative behavior with additional input. In contrast, dissolved 232Th showed a concave profile, indicating a net removal of 232Th during the mixing of fresh water with seawater. The behavior of Th isotopes in the <10 kDa fraction followed those in the dissolved phases. The difference in geochemical behaviors among three Th isotopes was ascribed to their different sources in the estuary.

China↗

PubMed2005

Tailoring aqueous solubility of functionalized single-wall carbon nanotubes over a wide pH range through substituent chain length.

Carboxylic acid-functionalized SWNTs prepared via the reaction of an amino acid, NH2(CH2)nCO2H, with fluoronanotubes show similar levels of sidewall functionalization; however, the solubility in water is controlled by the length of the hydrocarbon side chain (i.e., n). The 6-aminohexanoic acid derivative is soluble in aqueous solution (0.5 mg mL(-1)) between pH 4 and 11, whereas the glysine and 11-aminoundecanoic acid derivatives are insoluble across all pH values.

Amino Acids↗

PubMed2005

Glutathione depletion enhances the formation of endogenous cyclic DNA adducts derived from t-4-hydroxy-2-nonenal in rat liver.

Earlier, we detected the cyclic adducts of deoxyguanosine (dG) derived from t-4-hydroxy-2-nonenal (HNE), a long chain alpha,beta-unsaturated aldehyde (enal) product from oxidation of omega-6 polyunsaturated fatty acids, in tissue DNA of rats and humans as endogenous DNA damage. Recent evidence implicates the cyclic HNE adducts in human liver carcinogenesis. Because glutathione (GSH) protects against oxidative stress, we undertook a study to examine the effect of GSH depletion on the HNE-derived cyclic adducts in vivo. Four F344 rats were administered L-buthionine-(S,R)-sulfoximine (BSO), a potent inhibitor of GSH biosynthesis, at 10 mM in drinking water for 2 weeks. Rats in the control group were given water only. Livers were harvested, and each liver was divided into portions for GSH and DNA adduct analyses. The BSO treatment depleted hepatic GSH by 77%; the GSH levels were reduced from 6.3 +/- 0.3 in the control rats to 1.5 +/- 0.1 micromol/g tissues in the treated group. The formation of HNE-dG adducts, analyzed by an HPLC-based 32P-postlabeling assay, was increased by 4-fold, from 6.2 +/- 2.2 nmol/mol dG in liver DNA of control rats to 28.5 +/- 16.1 nmol/mol dG in the rats treated with BSO (p <0.05). The formation of 8-oxodG in liver DNA was also increased as a result of BSO treatment, although the increase was not statistically significant. These results further support the endogenous origin of HNE-dG adducts and, more importantly, indicate a critical role that GSH plays in protecting against in vivo formation of the promutagenic cyclic DNA adducts derived from HNE.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

The Neuroprotection of puerarin against cerebral ischemia is associated with the prevention of apoptosis in rats.

Previous work has shown that puerarin (Pur), extracted from the dried root of Pueraria lobata (Wild) Ohwi, increases cerebral blood flow in dogs and attenuates cerebral and spinal cord injury resulting from ischemia and reperfusion in rats and rabbits. The present study further demonstrates the neuroprotective effects of Pur on cerebral ischemic injury in rats and the mechanisms underlying the protective effects. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAo) for 50 min followed by reperfusion for 24 h. Pur (50, 100 mg/kg, i.p) was administered at the onset of MCAo. Twenty-four hours after reperfusion, neurological deficits were evaluated in Pur- and vehicle-treated rats. The infarct volume and edema ratios were assessed from stained brain slices. The results showed that Pur (100 mg/kg) markedly decreased the infarct volume by 34 % ( P < 0.01) in cerebral cortex and improved the neurological functions ( P < 0.05) after MCAo. Furthermore, flow cytometric analysis of annexin-V and PI labeling cells showed that the percentages of apoptosis and necrosis in the dorsolateral cortex were significantly reduced by 38.6 % and 28.5 % ( P < 0.01 and P < 0.05) following treatment with Pur (100 mg/kg) in MCAo rats. Caspase-3 activity, a biochemical marker of apoptosis, was significantly inhibited after treatment with Pur in the dorsolateral cortex. In agreement with this result, the expression of the X-chromosome-linked inhibitor of apoptosis protein (XIAP) was obviously up-regulated after administration of Pur (100 mg/kg), while caspase-3 gene was down-regulated in the dorsolateral cortex. These results suggest that the neuroprotection of puerarin against cerebral ischemia is associated with anti-apoptosis.

Animals↗

PubMed2005

Cloning and sequence analysis of myostatin promoter in sheep.

To better understand the structure and function of the myostatin's gene promoter region in sheep, we cloned and sequenced a 1.517 kb fragment containing the 5'-regulatory region of the sheep myostatin gene (GenBank accession number is AY918121). The promoter sequence consists of three TATA boxes, one CAAT box, and eight putative E-boxes. Some putative muscle growth response elements for Octamer-binding factor 1(Octamer), Activator protein 1(AP1), Growth factor independence 1 zinc finger protein (Gfi-1B), Myocyte enhancer factor 2 (MEF2), Muscle-specific Mt binding site (MTBF), Glucocorticoid response elements (GRE) and Progesterone receptor binding site (PRE) were detected. Some of the motifs are conserved as compared to with that in the goat, bovine and porcine myostatin promoters. However, some differences were also found.

Animals↗

PubMed2005

Color demosaicking via directional linear minimum mean square-error estimation.

Digital cameras sample scenes using a color filter array of mosaic pattern (e.g., the Bayer pattern). The demosaicking of the color samples is critical to the image quality. This paper presents a new color demosaicking technique of optimal directional filtering of the green-red and green-blue difference signals. Under the assumption that the primary difference signals (PDS) between the green and red/blue channels are low pass, the missing green samples are adaptively estimated in both horizontal and vertical directions by the linear minimum mean square-error estimation (LMMSE) technique. These directional estimates are then optimally fused to further improve the green estimates. Finally, guided by the demosaicked full-resolution green channel, the other two color channels are reconstructed from the LMMSE filtered and fused PDS. The experimental results show that the presented color demosaicking technique outperforms the existing methods both in PSNR measure and visual perception.

Algorithms↗

PubMed2005

Canny edge detection enhancement by scale multiplication.

The technique of scale multiplication is analyzed in the framework of Canny edge detection. A scale multiplication function is defined as the product of the responses of the detection filter at two scales. Edge maps are constructed as the local maxima by thresholding the scale multiplication results. The detection and localization criteria of the scale multiplication are derived. At a small loss in the detection criterion, the localization criterion can be much improved by scale multiplication. The product of the two criteria for scale multiplication is greater than that for a single scale, which leads to better edge detection performance. Experimental results are presented.

Algorithms↗

PubMed2005

An improved robust fuzzy-PID controller with optimal fuzzy reasoning.

Many fuzzy control schemes used in industrial practice today are based on some simplified fuzzy reasoning methods, which are simple but at the expense of losing robustness, missing fuzzy characteristics, and having inconsistent inference. The concept of optimal fuzzy reasoning is introduced in this paper to overcome these shortcomings. The main advantage is that an integration of the optimal fuzzy reasoning with a PID control structure will generate a new type of fuzzy-PID control schemes with inherent optimal-tuning features for both local optimal performance and global tracking robustness. This new fuzzy-PID controller is then analyzed quantitatively and compared with other existing fuzzy-PID control methods. Both analytical and numerical studies clearly show the improved robustness of the new fuzzy-PID controller.

Algorithms↗

PubMed2005

Establishment and partial characterization of five malignant glioma cell lines.

Five malignant glioma cell lines (YMG1, 2, 3, 4, and 5) were established from surgical specimens obtained from patients with glioblastoma or anaplastic astrocytoma, and these lines were partially characterized. Three glioma cell lines (YMG1, 3, and 5) were weakly positive for GFAP by Western blot analysis and two cell lines were negative. S-100 protein was positive in all glioma cell lines. The expression of p53, p16, p15, cyclin-dependent kinase 4 (CDK4), and EGF receptor (EGFR) proteins was examined by Western blotting. YMG1 and 2 cell lines showed accumulation of p53 protein and loss of p16 and p15 expression. YMG3 and 4 showed accumulation of p53 protein and expression of p16 and p15 proteins. YMG5 revealed weak expression of p53 protein, suggesting wild-type p53, and loss of p16 and p15 expression. All cell lines expressed various levels of CDK4 protein. YMG1, 2, and 3 showed higher EGFR protein expression and YMG4 and 5 showed lower EGFR expression compared to U251 glioblastoma cells, which express high levels of EGFR. Fluorescence in situ hybridization analysis for EGFR gene expression did not show any amplification in the glioma cell lines. Immunohistochemical studies revealed that the patterns of p53 and EGFR expressions in the original tumor tissues were mostly correlated with those in the malignant glioma cell lines. These results suggest that the characteristics of p53 and EGFR expression in the malignant glioma cell lines were passed over from the original tumor tissues. These newly established malignant glioma cell lines can be used for further analysis of the mechanisms of tumor growth and progression.

Adult↗

PubMed2005

Heightened responses to stressors in patients with inflammatory bowel disease.

OBJECTIVES: Several studies suggest that stressful situations (stressors) worsen the course of inflammatory bowel disease (IBD), but the mechanism is not known. Based on several lines of evidence, we hypothesized that psychosocial stress activates the brain-gut axis (BGA) and mucosal mast cells (MC), and activated MC produce proinflammatory cytokines. To test this hypothesis, we determined whether stressor-induced activation of BGA is exaggerated in IBD patients. METHODS: Stress was induced in 15 IBD patients who were in remission (inactive IBD) and in seven controls by a widely used stressor, the cold pressor test (CPT), daily for five consecutive days. Induction of stress was confirmed objectively by measurement of stress hormones (serum cortisol and ACTH), and hemodynamic parameters and subjectively by questionnaire. Activation of the BGA by this stressor was assessed by evaluating colonic mucosal MC histology and degranulation, using electron microscopy (EM). The effects of the stressor on the intestinal mucosa were assessed by changes in inflammatory cell histology, epithelial mitochondria (EM), and oxidative tissue injury (assays for protein oxidation). RESULTS: In both study groups, the stressor resulted in (1) increased levels of stress hormones, (2) the expected changes in hemodynamic parameters, (3) activation and degranulation of MC, (4) mitochondrial damage to epithelial cells, and (5) mucosal protein oxidation. These changes were more marked in IBD patients. CONCLUSIONS: The heightened response to the stressors and the greater epithelial damage in IBD patients suggests that stress-induced activation of the BGA and of mucosal MC is important in the initiation and/or flare up of IBD.

Adrenocorticotropic Hormone↗

PubMed2005

Distribution of cysteinyl leukotriene receptor 2 in human traumatic brain injury and brain tumors.

AIM: To determine the distribution of cysteinyl leukotriene receptor 2 (CysLT2), one of the cysteinyl leukotriene receptors, in human brains with traumatic injury and tumors. METHODS: Brain specimens were obtained from patients who underwent brain surgery. CysLT2 in brain tissues was examined using immunohistochemical analysis. RESULTS: CysLT2 was expressed in the smooth muscle cells (not in the endothelial cells) of arteries and veins. CysLT2 was also expressed in the granulocytes in both vessels and in the brain parenchyma. In addition, CysLT2 was detected in neuron- and glial-appearing cells in either the late stages of traumatic injury or in the area surrounding the tumors. Microvessels regenerated 8 d after trauma and CysLT2 expression was recorded in their endothelial cells. CONCLUSION: CysLT2 is distributed in vascular smooth muscle cells and granulocytes, and brain trauma and tumor can induce its expression in vascular endothelial cells and in a number of other cells.

Adolescent↗