Biomedical subjects

Lei Wang

Publications and source records attributed to Lei Wang.

At least 307 records · Page 17Linked to original sources

PubMed2004

1-(4-Bromophenyl)-3-(4-methylphenyl)prop-2-en-1-one.

In the molecule of the title compound, C16H13BrO, the two benzene rings are rotated in opposite directions with respect to the central C-C=C-C part of the molecule. The phenone O atom deviates from the least-squares plane of the molecule by 0.300 (3) A. In the crystal structure, molecules are paired through C-H...pi interactions. The molecular pairs along [001] are hydrogen bonded through three translation-related co-operative hydrogen bonds in the 'bay area', forming molecular chains, which are further hydrogen bonded through C-H...Br weak interactions, forming (010) molecular layers. In the third direction, there are only weak van der Waals interactions. The co-operative hydrogen bonds in the 'bay area' are discussed briefly.

Journal Article↗

PubMed2004

Phototoxicity and DNA damage induced by the cosmetic ingredient chemical azulene in human Jurkat T-cells.

Previous study showed that the cosmetic ingredient chemical azulene and its derivative gauiazulene exhibited photomutagenicity four- to five-fold higher than spontaneous mutation in Salmonella typhimurium TA102. In this study, phototoxicity including photogenotoxicity of azulene in human Jurkat T-cells is reported. When the cell suspensions are irradiated by light (UVA plus visible light) in the presence of azulene, an azulene dose-dependent cellular DNA damage is observed. At the highest azulene concentration of 50 microM, the average DNA fragmentation is 33 +/- 10%, determined by single cell gel electrophoresis (Comet assay). Cell viability assay using fluorescein diacetate indicates that the cells could endure the damage and remain viable. Further study revealed that the combination of light and azulene can cause single-strand cleavage on pure PhiX174 plasmid DNA in solution. Studies using scavengers reveal that singlet oxygen and free radicals are involved in causing DNA cleavage. This suggests that the photomutagenicity of azulene in S. typhimurium TA102 could be due to DNA fragmentation caused by the concurrent exposure to azulene and light.

Azulenes↗

PubMed2004

Down-regulation of p27kip1 increases proliferation of progenitor cells in adult rats.

Cyclin-dependent kinases (CDK) mediate the cell division cycle during G1 phase and CDK inhibitors negatively regulate the cell cycle. We investigated expression of the CDK inhibitor p27Kip1 and the effects of PI-3K/Akt on proliferation of progenitors in the subventricular zone of adult rat. Western blots and immunostaining revealed that 4 days after stroke, p27kip1 levels decreased and were absent in nuclei of the ipsilateral subventricular zone cells 7 days after stroke. Reduction in p27kip1 levels was concurrent with significant increases in BrdU immunoreactive cells in the subventricular zone. Treatment of stroke neurospheres with LY294002 significantly (p<0.05) reduced the numbers of neurospheres from 32 +/-5 in the stroke group to 14 +/- 3 in the stroke and LY294002 group. Collectively, our data suggest that stroke induced neural progenitor proliferation is mediated by down-regulation of p27Kip1 and activation of Akt.

Animals↗

PubMed2004

Evidence of MKK4 pro-oncogenic activity in breast and pancreatic tumors.

MKK4, located in close proximity to p53 gene, is thought to be a tumor suppressor and a metastasis suppressor gene. A low-rate MKK4 gene alteration has been found in a few tumor types, including breast and pancreatic. A suppressor activity for prostate and ovarian tumor metastasis has also been suggested. To understand the pathobiologic roles of MKK4 in tumorigenesis, we examined the phenotypic changes in response to perturbation of the MKK4 expression in breast and pancreatic cancer cell lines. Ectopic expression of MKK4 by adenoviral delivery in MKK4-negative cancer lines stimulated the cell proliferation and invasion, whereas knockdown of MKK4 expression by small interference RNA in an MKK4-positive breast cancer cell line, MDA-MB-231, resulted in decreased anchorage-independent growth, suppressed tumor growth in mouse xenograft model, and increased cell susceptibility to apoptosis brought by stress signals such as serum deprivation. These results argue that MKK4 functions as a pro-oncogenic molecule instead of a suppressor in breast and pancreatic tumors.

Animals↗

PubMed2004

MRI-based high-dimensional hippocampal mapping in mesial temporal lobe epilepsy.

MRI-based evaluation of the hippocampus is important in the assessment and treatment of patients with mesial temporal lobe epilepsy (MTLE). Using MRI-based large-deformation high-dimensional mapping (HDM-LD), which allows structural evaluation of regions of the hippocampus, we document the HDM-LD-defined pattern of hippocampal deformation in MTLE patients compared with matched controls. In 30 subjects with MTLE and confirmed medial temporal lobe sclerosis (MTS), we performed measurements of intracranial area, brain parenchymal volume and deformation-based hippocampal segmentations, and then grouped patients into right and left MTS groups (resulting in 15 subjects in each group). Using HDM-LD techniques, we compared the right and left MTS groups with a group of 15 matched controls. Analysis included both the MTS and contralateral hippocampi, and covariance for changes in brain parenchymal volume. Final results were interpreted using a segmentation showing normal hippocampal surface subfield anatomy. Comparing the MTS groups with controls, after covarying with brain parenchymal volume, the MTS hippocampi showed significant volume loss (P < 0.0001), contralateral hippocampi showed no significant volume loss. HDM-LD techniques showed significant shape changes, with marked inward deviation in the Sommer sector of the MTS hippocampi. In the contralateral hippocampi, the inferior surface of the hippocampal body showed inward deformation in the medial aspect of the subiculum, with minimal involvement of the Sommer sector. HDM-LD shows involvement of subregions of the hippocampus which are consistent with MTS histopathology. Contralateral hippocampi show different HDM-LD changes, suggesting that the underlying disease process in the contralateral hippocampi is different from MTS.

Adult↗

PubMed2004

Erythropoietin up-regulates SOCS2 in neuronal progenitor cells derived from SVZ of adult rat.

We examined the effects of EPO on expression of suppressor of cytokine signaling 2 (SOCS2) and found that treatment of neural progenitor cells derived from the adult subventricular zone (SVZ) with recombinant human EPO (rhEPO) stimulated progenitor cell differentiation into neurons, but not astrocytes. Quantitative RT-PCR revealed that SOCS2 mRNA levels were increased in the progenitor cells treated with rhEPO. Immunostaining showed that neurons but not astrocytes were SOCS2 immunoreactive. Incubation of the progenitor cells with rhEPO in the presence of a neutralizing antibody against EPO abolished the effects of EPO on neuronal differentiation and expression of SOCS2. Our data suggest that up-regulation of SOCS2 in neuronal progenitor cells derived from the adult SVZ may regulate EPO enhanced neuronal differentiation.

Animals↗

PubMed2004

Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats.

BACKGROUND AND PURPOSE: Erythropoietin (EPO) promotes proliferation and differentiation of erythroid progenitors and the survival of maturing erythroid cells. Here, we investigated the role of EPO in brain repair after stroke. METHODS: Rats were treated with recombinant human EPO (rhEPO) at 24 hours after the onset of embolic stroke. An array of behavior tests was performed. Rats were euthanized 28 days after stroke for measurements of infarct volume, angiogenesis, and neurogenesis. In vitro, neurospheres derived from the subventricular zone (SVZ) of the rat and cerebral endothelial cells derived from the mouse were treated with rhEPO. Capillary-like tube formation and neuronal differentiation were measured. RESULTS: Treatment with rhEPO significantly improved functional recovery, along with increases in density of cerebral microvessels at the stroke boundary and numbers of BrdU, doublecortin, and nestin immunoreactive cells in the SVZ. rhEPO treatment significantly increased brain levels of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). In vitro, rhEPO enhanced capillary tube formation of cerebral endothelial cells, which was inhibited by a specific VEGF receptor 2 antagonist (SU1498). Incubation of neurospheres derived from stroke SVZ with anti-EPO neutralizing antibody inhibited neurogenesis, whereas incubation of stroke-derived neurospheres with rhEPO enhanced neurogenesis. CONCLUSIONS: Our data suggest that EPO-increased VEGF and BDNF may be involved in angiogenesis and neurogenesis, which could contribute to functional recovery.

Angiogenesis Inducing Agents↗

PubMed2004

The O-antigen gene cluster of Shigella boydii O11 and functional identification of its wzy gene.

Shigella strains are human pathogens and their identification is usually based on their O-antigens. The O-antigen gene cluster of Shigella boydii O11 was sequenced. All the expected genes for the synthesis of the O-antigen were identified on the basis of homology and genes for the biosynthesis of dTDP-l-Rhamnose, genes encoding sugar transferases, as well as genes encoding O unit flippase (wzx) and O-antigen polymerase (wzy). The identity of the putative wzy gene was confirmed by showing that a wzy deficient mutant strain of S. boydii O11 produced a semi-rough LPS phenotype. The predicted wzx gene has an opposite transcription direction to that of all of the other genes in the S. boydii O11 O-antigen gene cluster. This unusual feature for the wzx gene has only previously been reported in S. boydii O6. Further comparison revealed an evolutionary relationship between O6 and O11 O-antigen gene clusters. Adjacent-gene PCR showed that Escherichia coli O105 and S. boydii O11, which share the identical O-antigen, also have the same genes and organization for their respective O-antigen gene clusters. Three genes specific for the S. boydii O11 and E. coli O105 gene clusters were identified.

Bacterial Proteins↗

PubMed2004

Dynein light chain LC8 promotes assembly of the coiled-coil domain of swallow protein.

LC8 is a highly conserved light-chain subunit of cytoplasmic dynein that is thought to play a fundamental role in both the assembly of the motor complex and the recruitment of cargo. An interaction between LC8 and the Drosophila protein swallow has been previously characterized and supports a role for dynein in the localization of maternal morphogens during oogenesis. Swallow is required for the proper localization of bicoid mRNA, the anterior determinant that plays a critical role in establishment of the Drosophila embryonic axis. In this work, we prepared constructs of swallow, each containing a predicted coiled-coil domain and variable surrounding segments that lie within the domain proposed to interact with LC8. The interaction between LC8 and swallow domains was characterized by glutathione S-transferase (GST) pull-down assays, limited proteolysis followed by mass spectrometry, and circular dichroic spectroscopy. Hydrodynamic measurements, covalent cross-linking, and circular dichroic spectroscopy show that this domain of swallow is an unstable dimeric coiled-coil. Upon LC8 binding, however, the coiled-coil becomes significantly more stable. A possible general role for LC8 in macromolecular assembly is discussed.

Amino Acid Sequence↗

PubMed2004

Identification and characterization of a novel nasopharyngeal carcinoma-associated peptide: NAP-1.

Nasopharyngeal carcinoma (NPC) is one of the most commons cancers in Southeast Asia and Southern China. Several NPC-associated genes have been so far described and here we describe the identification and the characterization of a novel nasopharyngeal carcinoma-associated peptide: NAP-1. NAP-1 was identified with the human genome draft searching method combined with nested PCR mapping of the chromosome 4q13 region. NAP-1 encodes an 85 amino acid alkaline peptide with a calculated isoelectric point of 9.3, three phosphorilation sites and a proline-rich region. Northern blot analysis revealed that NAP-1 is expressed as a 0.6 kb transcript in normal lymph nodes and trachea. In addition, reverse transcription (RT)-PCR showed that NAP-1 is expressed not only in NPC but in normal nasopharynx (NP) and various other tumors and tissues of the head and neck including: tonsils, lymph nodes, carcinoma of the tonsil, T cell lymphomas, squamous cell carcinoma of the hard palate, papilloma of the nasopharynx, nasopharyngitis, lymphoma of the tongue root and follicular dendritic cells (FDC). In addition, NAP-1 is not expressed in normal tissues or tumors from other anatomical regions and was not expressed by NPC cell lines. Surprisingly, differential RT-PCR demonstrated decreased expression of NAP-1 in NPC compared with paired NP biopsies in 42.5 % of cases (17 out of 40). In addition, in situ hybridization and immunohistochemistry demonstrated that NAP-1 is expressed by S100+ CD35+ FDCs of the germinal center and not in other normal immune cells infiltrating NP or NPC. Therefore, it is likely that NAP-1 is secreted by FDC in the NP and may play an immune modulatory role in NPC.

Journal Article↗

PubMed2004

High-level secretory production of recombinant bovine enterokinase light chain by Pichia pastoris.

Enterokinase (EC 3.4.21.9) is a serine proteinase with a specific digest sequence (Asp)4-Lys in the duodenum. Its high specificity for the recognition site makes enterokinase (EK) a useful tool for an in vitro cleavage of fusion proteins. In this work, an active bovine enterokinase light chain (EK(L)) was produced in secretory form by a recombinant strain of the methylotrophic yeast Pichia pastoris. The influences of methanol utilization phenotype of the host strain, induction pH, and carbon source on the recombinant production were studied. The production of recombinant EK(L) by Mut(s) strain was much higher than that by Mut+ strain. When inducted at pH 6.0, on a glycerol/methanol medium, the concentration of recombinant EK(L) (rEK(L)) reached 350 mg l(-1), which was 20-fold higher than that reported previously. The recombinant EK(L) was purified in a simple procedure on the anion exchange chromatography and 15 mg pure active EK(L) were obtained from 100 ml culture broth supernatant. The specific activity of purified rEK(L) was approximately 9000 u mg(-1). To facilitate purification and removal of rEKL after cleavage of fusion protein, the C-terminal His-tagged EK(L) (EK(L)/His) was also expressed in P. pastoris, and this His-tagged EK(L) exhibited a similar enzymatic activity to the untagged EK(L).

Animals↗

PubMed2004

A novel aminophospholipid transporter exclusively expressed in spermatozoa is required for membrane lipid asymmetry and normal fertilization.

Through the use of a functionally unbiased signal peptide trap screen, we have discovered an ATP-dependent aminophospholipid transporter that is exclusively expressed in the acrosomal region of spermatozoa; it is about 62% similar to the flippase, FIC1. We disrupted the transporter gene and found that the size of litters from male null mice was slightly smaller than found with wild-type males. Sperm morphology and motility were the same between null and wild-type littermates, but agents (merocyanine and annexin) that measure phospholipid packing or phosphatidylserine (PS) in the outer membrane leaflet showed that PS already existed in the outer leaflet of null spermatozoa before sperm capacitation. Fertilization rates were normal when null spermatozoa were added to zona pellucida-free eggs, but in the presence of the extracellular matrix, fewer transporter(-/-) spermatozoa bound tightly or penetrated the zona pellucida (ZP), and fewer underwent acrosome reactions. In vitro fertilization was compromised, especially at early time points or at low sperm concentrations after mixing null spermatozoa and eggs. Thus, a new aminophospholipid transporter expressed exclusively in spermatozoa is critical for normal phospholipid distribution in the bilayer, and for normal binding, penetration, and signaling by the zona pellucida.

Amino Acid Sequence↗

PubMed2004

Calcium mobilization and Rac1 activation are required for VCAM-1 (vascular cell adhesion molecule-1) stimulation of NADPH oxidase activity.

VCAM-1 (vascular cell adhesion molecule-1) plays an important role in the regulation of inflammation in atherosclerosis, asthma, inflammatory bowel disease and transplantation. VCAM-1 activates endothelial cell NADPH oxidase, and this oxidase activity is required for VCAM-1-dependent lymphocyte migration. We reported previously that a mouse microvascular endothelial cell line promotes lymphocyte migration that is dependent on VCAM-1, but not on other known adhesion molecules. Here we have investigated the signalling mechanisms underlying VCAM-1 function. Lymphocyte binding to VCAM-1 on the endothelial cell surface activated an endothelial cell calcium flux that could be inhibited with anti-alpha4-integrin and mimicked by anti-VCAM-1-coated beads. VCAM-1 stimulation of calcium responses could be blocked by an inhibitor of intracellular calcium mobilization, a calcium channel inhibitor or a calcium chelator, resulting in the inhibition of NADPH oxidase activity. Addition of ionomycin overcame the calcium channel blocker suppression of VCAM-1-stimulated NADPH oxidase activity, but could not reverse the inhibitory effect imposed by intracellular calcium blockage, indicating that both intracellular and extracellular calcium mobilization are required for VCAM-1-mediated activation of NADPH oxidase. Furthermore, VCAM-1 specifically activated the Rho-family GTPase Rac1, and VCAM-1 activation of NADPH oxidase was blocked by a dominant negative Rac1. Thus VCAM-1 stimulates the mobilization of intracellular and extracellular calcium and Rac1 activity that are required for the activation of NADPH oxidase.

Animals↗

PubMed2004

Noise statistics in optically preamplified differential phase-shift keying receivers with Mach-Zehnder interferometer demodulation.

We report an analysis of the noise statistics for an optically preamplified differential phase-shift keying (DPSK) receiver with balanced and single-port detections. It is found that identical signal-amplified spontaneous emission beating noise exists for bits 1 and 0 in DPSK balanced detection. It is also revealed that the bit error ratio (BER) of a DPSK receiver with balanced detection has no direct relation to the conventional Q factor. Moreover, an analytic BER expression for the DPSK balanced detection receiver is presented.

Journal Article↗

PubMed2004

Stationary phase protein overproduction is a fundamental capability of Escherichia coli.

Although Escherichia coli is well studied and various recombinant E. coli protein expression systems have been developed, people usually consider the rapid growing (log phase) culture of E. coli as optimum for production of proteins. However, here we demonstrate that at stationary phase three E. coli systems, BL21 (DE3)(pET), DH5alpha (pGEX) induced with lactose, and TG1 (pBV220) induced with heat shock could overexpress diversified genes, including three whose products are deleterious to the host cells, more stably and profitably than following the log phase induction protocol. Physical and patch-clamp assays indicated that characteristics of target proteins prepared from cultures of the two different growth phases coincide. These results not only provide a better strategy for recombinant protein preparation in E. coli, but also reveal that rapid rehabilitation from stresses and stationary phase protein overproduction are fundamental characters of E. coli.

Cell Division↗

PubMed2004

The Sonogashira coupling reaction catalyzed by ultrafine nickel(0) powder.

The Sonogashira coupling reaction catalyzed by ultrafine nickel(0) powder has been developed; terminal alkynes couple with aryl, alkenyl iodide and aryl bromide in the presence of cuprous iodide, triphenylphosphine, potassium hydroxide and ultrafine particle nickel(0) to provide the corresponding cross-coupling products with high yields.

Journal Article↗

PubMed2004

Photomutagenicity of 16 polycyclic aromatic hydrocarbons from the US EPA priority pollutant list.

The photomutagenicity of 16 polycyclic aromatic hydrocarbons (PAHs), all on the United States Environmental Protection Agency (US EPA) priority pollutant list, was studied. Concomitant exposing the Salmonella typhimurium bacteria strain TA102 to one of the PAHs and light (1.1 J/cm2 UVA+2.1 J/cm2 visible) without the activation enzyme S9, strong photomutagenic response is observed for anthracene, benz[a]anthracene, benzo[ghi]perylene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene, and pyrene. Under the same conditions, acenaphthene, acenaphthylene, benzo[k]fluoranthene, chrysene, and fluorene are weakly photomutagenic. Benzo[b]fluoranthene, fluoranthene, naphthalene, phenanthrene, and dibenz[a,h]anthracene are not photomutagenic. These results indicate that PAHs can be activated by light and become mutagenic in Salmonella TA102 bacteria. At the same time, the mutagenicity for all the 16 PAHs was examined with the standard mutagenicity test with 10% S9 as the activation system. Benzo[b]fluoranthene, benzo[k]fluoranthene, chrysene, acenaphthylene, and fluorene are weakly mutagenic, while the rest of the PAHs are not. In general, the photomutagenicity of PAHs in TA102 does not correlate with their S9-activated mutagenicity in either TA102 or TA98/TA100 since they involve different activation mechanisms.

Animals↗

PubMed2004

Using texture to analyze and manage large collections of remote sensed image and video data.

We describe recent research into using the visual primitive of texture to analyze and manage large collections of remote sensed image and video data. Texture is regarded as the spatial dependence of pixel intensity. It is characterized by the amount of dependence at different scales and orientations, as measured with frequency-selective filters. A homogeneous texture descriptor based on the filter outputs is shown to enable (1) content-based image retrieval in large collections of satellite imagery, (2) semantic labeling and layout retrieval in an aerial video management system, and (3) statistical object modeling in geographic digital libraries.

Journal Article↗