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Biomedical subjects

Ying Wang

Publications and source records attributed to Ying Wang.

At least 361 records · Page 20Linked to original sources
PubMed2004

Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5.

Mitogen-activated protein (MAP) kinases are essential regulators in immune responses, and their activities are modulated by kinases and phosphatases. MAP kinase phosphatase (MKP) is a family of dual-specificity phosphatases whose function is evolutionarily conserved. A number of mammalian MKPs have been identified so far, but their specific physiological functions in negative regulation of MAP kinases have not been genetically defined. Here we examine innate and adaptive immune responses in the absence of MKP5. JNK activity was selectively increased in Mkp5 (also known as Dusp10)-deficient mouse cells. Mkp5-deficient cells produced greatly enhanced levels of pro-inflammatory cytokines during innate immune responses and exhibited greater T-cell activation than their wild-type counterparts. However, Mkp5-deficient T cells proliferated poorly upon activation, which resulted in increased resistance to experimental autoimmune encephalomyelitis. By contrast, Mkp5-deficient CD4(+) and CD8(+) effector T cells produced significantly increased levels of cytokines compared with wild-type cells, which led to much more robust and rapidly fatal immune responses to secondary infection with lymphocytic choriomeningitis virus. Therefore, MKP5 has a principal function in both innate and adaptive immune responses, and represents a novel target for therapeutic intervention of immune diseases.

Animals↗
PubMed2004

Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression.

The differentiation-related gene-1 (Drg-1) was first identified as a gene strongly upregulated by induction of differentiation in colon carcinoma cells in vitro, and later the same gene was shown to suppress tumorigenicity of human bladder cancer cells in vivo. On the other hand, we and others have demonstrated that the Drg-1 gene suppresses prostate and colon cancer metastases in mouse models. In the context of such potential organ-specific differential function of the Drg-1 gene, the present study was designed to clarify the expression status, regulation and function of Drg-1 in the case of human breast cancer. We found that the expression of the Drg-1 protein was significantly reduced in breast tumor cells, particularly in patients with lymph node or bone metastasis as compared to those with localized breast cancer. Drg-1 expression also exhibited significant inverse correlation with the disease-free survival rate of patients and emerged as an independent prognostic factor. The downregulation of the Drg-1 gene appeared to be largely at the RNA level, and the DNA methylation inhibitor, 5-Azacytidine, significantly elevated the Drg-1 gene expression in various breast tumor cell lines. Furthermore, we found that overexpression of the Drg-1 gene suppresses the invasiveness of breast cancer cells in vitro, and this suppression was also achieved by treatment of cells with 5-Azacytidine. Together, our results strongly suggest functional involvement of the Drg-1 gene in suppressing the metastatic advancement of human breast cancer.

Breast Neoplasms↗
PubMed2004

Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is characterized by intrusive and senseless thoughts and impulses (obsessions) and by repetitive behaviors (compulsions). Family, twin, and segregation studies support the presence of both genetic and environmental susceptibility factors, and the only published genome scan for OCD identified a candidate region on 9p24 at marker D9S288 that met criteria for suggestive significance (Hanna et al. 2002). In an attempt to replicate this finding, we genotyped 50 pedigrees with OCD, using microsatellite markers spanning the 9p24 candidate region, and analyzed the data, using parametric and nonparametric linkage analyses under both a narrow phenotype model (DSM-IV OCD definite; 41 affected sib pairs) and a broad phenotype model (DSM-IV OCD definite and probable; 50 affected sib pairs). Similar to what was described by Hanna et al. (2002), our strongest findings came with the dominant parameters and the narrow phenotype model: the parametric signal peaked at marker D9S1792 with an HLOD of 2.26 ( alpha =0.59), and the nonparametric linkage signal (NPL) peaked at marker D9S1813 with an NPL of 2.52 (P=.006). These findings are striking in that D9S1813 and D9S1792 lie within 0.5 cM (<350 kb) of the original 9p24 linkage signal at D9S288; furthermore, pedigree-based association analyses also implicated the 9p24 candidate region by identifying two markers (D9S288 and GATA62F03) with modest evidence (P=.046 and .02, respectively) for association.

Chromosome Mapping↗
PubMed2004

The effects of curing history on residual stresses in bone cement during hip arthroplasty.

During cement curing in total hip arthroplasty, residual stresses are introduced in the cement mantle as a result of curing shrinkage, thermal shrinkage, and geometrical constraints. These high residual stresses are capable of initiating cracks in the mantle of cemented hip replacements. The purpose of this study was to determine the residual stresses in the cemented hip replacements. The finite element method was developed to predict the residual stresses built up in joint arthroplasties. Experimental tests were then performed to validate the numerical methodology. Then the effects of curing history on the residual stress distribution were investigated with finite element simulations. Results showed that the predictions of the thermal shrinkage residual stresses by the developed method agreed with the experimental tests very well. The residual stress buildup was shown to depend on the curing history. By preheating the prosthesis stem prior to implantation, a desired low-level residual stress at the critical prosthesis-cement interface was obtained. As a result, this article provides a numerical tool for the quantitative simulation of residual stress and for examining and refining new designs computationally.

Arthroplasty, Replacement, Hip↗
PubMed2004

Contribution of C3d-P28 repeats to enhancement of immune responses against HBV-preS2/S induced by gene immunization.

AIM: To investigate whether P28 derived from C3d can enhance the immune response to HBV-preS2/S induced by directly injection of naked plasmids containing variable repeats of P28 and HBV-preS2/S in fusion form. METHODS: One to four copies of C3d-P28 coding gene, amplified by PCR and modified by restriction endonucleases digestion, were subcloned into a eukaryotic expression vector pVAON33 to construct pVAON33-P28, pVAON33-P28.2, pVAON33-P28.3 and pVAON33-P28.4 (pVAON33-P28.[1-4]). HBV-preS2/S coding sequence was then introduced into the pVAON33-P28.[1-4] and identified by both PCR and DNA sequencing. BALB/c mice were primed by intramuscular gene immunization with 100 microg different recombinant plasmids on day 0 and were boosted by subcutaneous inoculation with HBsAg protein (1 microg) 12 wk post-priming. The levels and avidity of specific IgG in sera collected at the indicated times from each group were determined by ELISA and NaSCN-displacement ELISA, respectively. RESULTS: HBsAg specific antibody response was elicited in groups primed with plasmids pVAON33-S2/S-P28.[1-4] and pVAON33-S2/S. However, the response against HBsAg in the groups primed with pVAON33-S2/S-P28.[1-4] was significantly higher than that in pVAON33-S2/S group, the highest level of the specific antibody response was observed in the groups primed with pVAON33-S2/S-P28.4 (P<0.01). After secondary immunization with specific antigen, the acceleration of antibody levels was significantly higher and faster in the mice primed with DNA expressing preS2/S-P28 fusions than that with DNA expressing preS2/S only (P<0.05). Interestingly, mice primed with DNA expressing preS2/S-P28.4 fusions maintained the highest levels of anti-HBs antibodies in all animals. The avidity assay showed that the avidity index (AI) collected at 18 wk from mice primed with pVAON33-S2/S-P28.3 and pVAON33-S2/S-P28.4 were significantly higher than that from preS2/S-DNA vaccinated mice (P<0.01). CONCLUSION: Different repeats of C3d-P28 can enhance both humoral immune response and avidity maturation of specific antibodies induced by gene immunization, in which four copies of C3d-P28 may be necessary to achieve the most modest antibody response.

Animals↗
PubMed2004

Stroke transiently increases subventricular zone cell division from asymmetric to symmetric and increases neuronal differentiation in the adult rat.

The orientation of mitotic cleavage regulates neurogenesis during neural development. We examined the orientation of mitotic cleavage of dividing progenitor cells in the subventricular zone (SVZ) of adult rats subjected to stroke. In nonstroke rats, 55% of dividing cells were oriented horizontally, whereas 40% were oriented vertically. Horizontal and vertical cleavage orientations produce asymmetric and symmetric divisions, respectively. Four days after stroke, the number of dividing cells increased twofold, whereas the proportion of symmetric dividing cells significantly (p < 0.01) increased from 40% before stroke to 60%. Fourteen days after stroke, the percentage of symmetric dividing cells was 47%. Stroke-increased numbers of dividing cells in M-phase were confirmed by immuostaining. In nonstroke rats, 37 and 33% of symmetric and asymmetric dividing cells, respectively, exhibited a neuronal marker (TuJ1). Four days after stroke, rats exhibited a significant (p < 0.05) augmentation of the frequency (47%) of neuronal distribution showing TuJ1 immunoreactivity in cells with symmetric division but not cells with asymmetric division (33%). Numb immunoreactivity was detected in SVZ cells of nonstroke rats. Stroke did not change Numb distribution. Our data suggest that neurons are produced by both asymmetric and symmetric cell divisions in the adult SVZ, and the transient increases in symmetric division and neuronal differentiation may result in stroke-induced neurogenesis.

Animals↗
PubMed2004

Crystal engineering of a versatile building block toward the design of novel inorganic-organic coordination architectures.

Six novel inorganic-organic coordination supramolecular networks based on a versatile linking unit 4-pyridylthioacetate (pyta) and inorganic Co(II), Cu(II), Ag(I), Zn(II), Mn(II) and Pb(II) salts have been prepared in water medium and structurally characterized by single-crystal X-ray diffraction analysis. Reaction of CoCl(2).6H(2)O with Hpyta afforded a neutral mononuclear complex [Co(pyta)(2)(H(2)O)(4)](1), which exhibits a two-dimensional (2-D) layered architecture through intermolecular O-HO interactions. Reaction of CuCl(2.2H(2)O with Hpyta yielded a neutral one-dimensional (1-D) coordination polymer [[Cu(pyta)(2)(H(2)O].0.5H(2)O](n)(2) consisting of rectangle molecular square units, which show a three-dimensional (3-D) supramolecular network through S...S and O-H...O weak interactions. However, when AgNO(3), Zn(OAc)(2).2H(2)O or MnCl(2).4H(2)O salts were used in the above self-assembled processes, the neutral 2-D coordination polymers [Ag(pyta)](n)(3), [[Zn(pyta)(2)].4H(2)O](n)(4) or [[Mn(pyta)(2)(H(2)O)]](n)(5) with different topologies were obtained, respectively. While substituting the transition metal ions used in 1-5 with Pb(OAc)(2).3H(2)O, a one-dimensional coordination polymer [Pb(pyta)(2)](n)(6), which shows a novel 2-fold interpenetrating 2-D supramolecular architecture through weak SS interactions, was isolated. It is interesting to note that the building block pyta anion exhibits different configurations and coordination modes in the solid structures of complexes 1-6. These results indicate that the versatile nature of this flexible ligand, together with the coordination preferences of the metal centers, play a critical role in construction of these novel coordination polymers or supramolecules. The spectral and thermal properties of these new materials have also been investigated.

Journal Article↗
PubMed2004

Diverse effects of long-term treatment with imidapril and irbesartan on cell growth signal, apoptosis and collagen type I expression in the left ventricle of spontaneously hypertensive rats.

To compare diverse effects of angiotensin II type 1 receptor antagonists (irbesartan) and angiotensin converting enzyme inhibitors (imidapril) on left ventricular remodeling in spontaneously hypertensive rats (SHR). Thirty male SHR were randomly divided into three groups: SHR-IR (treated with irbesartan, 50 mg/kg), SHR-IM (imidapril, 3 mg/kg), SHR-C (placebo). Ten male Wistar Kyoto rats (WKY) treated with placebo acted as the control. All treatments were administered once daily from 14 to 27 weeks of age. Imidapril and irbesartan have the similar inhibitor effects on blood pressure and left ventricular mass indexes in SHR. Despite both drugs suppressed ERK-1 protein expression, decreased cardiomyocytes apoptosis index, blocked collagen type I deposition, reduced TGF-beta(1) gene expression in SHR, imidapril elicits a stronger inhibitory effect. Irbesartan had little effect on MKP-1 protein expression, but imidapril decreased it significantly. As a result, the ERK-1/MKP-1 ratio in SHR-IR was significantly greater than that in SHR-IM (P < 0.05). These results suggest that the balance between MKP-1 and ERKs in myocardial tissue is important for cardiac cell proliferation and growth. They also indicate that the similar efficacy of antihypertensive treatment in reducing blood pressure does not predict the similar capacity to control the individual facet of left ventricular remodeling. Irbesartan is more effective in regressing the homeostasis between ERK-1 and MKP-1, however imidapril is superior in suppressing apoptosis and collagen synthesis in cardiac tissue.

Angiotensin II Type 1 Receptor Blockers↗
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

Water sorption properties of extruded zein films.

Water interactions in extruded zein films were investigated through moisture sorption isotherms. Sorption isotherms of zein products were affected by composition and structure morphology. Zein powder showed moisture sorption hysteresis, which was not observed in extruded samples. Extruded samples held less moisture than zein powder, while films containing oleic acid showed further reduction in moisture uptake. Brunauer, Emmett, and Teller (BET) and Guggenheim, Anderson, and De Boer (GAB) models fitted well the moisture sorption isotherms of zein products. Monolayer values estimated by BET and GAB models were consistent with predictions based on zein structural models. Water vapor permeability (WVP) of zein films was affected by the relative humidity of testing environment. Higher relative humidity resulted in higher WVP.

Absorption↗
PubMed2004

Ras and Gpa2 mediate one branch of a redundant glucose signaling pathway in yeast.

Addition of glucose to starved yeast cells elicits a dramatic restructuring of the transcriptional and metabolic state of the cell. While many components of the signaling network responsible for this response have been identified, a comprehensive view of this network is lacking. We have used global analysis of gene expression to assess the roles of the small GTP-binding proteins, Ras2 and Gpa2, in mediating the transcriptional response to glucose. We find that 90% of the transcriptional changes in the cell attendant on glucose addition are recapitulated by activation of Ras2 or Gpa2. In addition, we find that protein kinase A (PKA) mediates all of the Ras2 and Gpa2 transcriptional effects. However, we also find that most of the transcriptional effects of glucose addition to wild-type cells are retained in strains containing a PKA unresponsive to changes in cAMP levels. Thus, most glucose-responsive genes are regulated redundantly by a Ras/PKA-dependent pathway and by one or more PKA-independent pathways. Computational analysis extracted RRPE/PAC as the major response element for Ras and glucose regulation and revealed additional response elements mediating glucose and Ras regulation. These studies provide a paradigm for extracting the topology of signal transduction pathways from expression data.

Alleles↗
PubMed2004

Uncoupling conformational change from GTP hydrolysis in a heterotrimeric G protein alpha-subunit.

Heterotrimeric G protein alpha (G alpha) subunits possess intrinsic GTPase activity that leads to functional deactivation with a rate constant of approximately 2 min(-1) at 30 degrees C. GTP hydrolysis causes conformational changes in three regions of G alpha, including Switch I and Switch II. Mutation of G202-->A in Switch II of G alpha(i1) accelerates the rates of both GTP hydrolysis and conformational change, which is measured by the loss of fluorescence from Trp-211 in Switch II. Mutation of K180-->P in Switch I increases the rate of conformational change but decreases the GTPase rate, which causes transient but substantial accumulation of a low-fluorescence G alpha(i1).GTP species. Isothermal titration calorimetric analysis of the binding of (G202A)G alpha(i1) and (K180P)G alpha(i1) to the GTPase-activating protein RGS4 indicates that the G202A mutation stabilizes the pretransition state-like conformation of G alpha(i1) that is mimicked by the complex of G alpha(i1) with GDP and magnesium fluoroaluminate, whereas the K180P mutation destabilizes this state. The crystal structures of (K180P)G alpha(i1) bound to a slowly hydrolyzable GTP analog, and the GDP.magnesium fluoroaluminate complex provide evidence that the Mg(2+) binding site is destabilized and that Switch I is torsionally restrained by the K180P mutation. The data are consistent with a catalytic mechanism for G alpha in which major conformational transitions in Switch I and Switch II are obligate events that precede the bond-breaking step in GTP hydrolysis. In (K180P)G alpha(i1), the two events are decoupled kinetically, whereas in the native protein they are concerted.

Amino Acid Substitution↗
PubMed2004

The 5'-upstream region of human programmed cell death 5 gene contains a highly active TATA-less promoter that is up-regulated by etoposide.

The PDCD5 (programmed cell death 5), a novel apoptosis related gene, is functionally associated with cell apoptosis, exhibits a ubiquitous expression pattern and is up-regulated in some types of tumor cells undergoing apoptosis. To study the transcriptional regulation of the PDCD5 gene, we have cloned 1.1 kb of its 5'-upstream region. The DNA sequencing analysis revealed a major transcriptional start site at 72 base pairs in front of the ATG translational start codon. The upstream of the transcriptional start site lacks a canonical TATA box and CAAT box. Transient transfection and luciferase assay demonstrate that this region presents extremely strong promoter activity. The 5'-deleted sequences fused to a luciferase reporter gene demonstrated that the -555/-383 region from the transcription start site is crucial for transcriptional regulation, and the luciferase reporter gene's expression significantly increased in the early stage of cell apoptosis induced by etoposide. These results imply that the PDCD5 gene may be a target gene under the control of some important apoptosis-related transcriptional factors during the cell apoptosis.

5' Flanking Region↗
PubMed2004

An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression.

Accumulating reports demonstrate that apoptosis does not explain all the forms of programmed cell death (PCD), particularly in individual development and neurodegenerative disease. Recently, a novel type of PCD, designated 'paraptosis', was described. Here, we show that overexpression of TAJ/TROY, a member of the tumor necrosis factor receptor superfamily, induces non-apoptotic cell death with paraptosis-like morphology in 293T cells. Transmission electron microscopy studies reveal extensive cytoplasmic vacuolation and mitochondrial swelling in some dying cells and no condensation or fragmentation of the nuclei. Characteristically, cell death triggered by TAJ/TROY was accompanied by phosphatidylserine externalization, loss of the mitochondrial transmembrane potential and independent of caspase activation. In addition, TAJ/TROY suppressed clonogenic growth of HEK293 and HeLa cells. Interestingly, overexpression of Programmed cell death 5 (PDCD5), an apoptosis-promoting protein, enhanced TAJ/TROY-induced paraptotic cell death. Moreover, cellular endogenous PDCD5 protein was significantly upregulated in response to TAJ/TROY overexpression. These results provide novel evidence that TAJ/TROY activates a death pathway distinct from apoptosis and that PDCD5 is an important regulator in both apoptotic and non-apoptotic PCD.

Apoptosis↗
PubMed2004

An improved method for acute isolation of neurons from the hippocampus of adult rats suitable for patch-clamping study.

An improved method is described for fast and reliable isolation of neurons from hippocampus of adult rats by a combination of mechanical and enzymatic means. The procedure allows the isolation of neurons from 500-600-d-old rats (over 300 g), preserving the proximal dendritic structure without impairing the electrical characteristics of the cells. Morphologically distinct neurons can be recognized. Using cell-attached, inside-out and whole-cell configurations of patch clamp technique, it was shown that the enzymatically isolated neurons in hippocampus from rats weighing more than 300 g exhibited voltage-gated calcium, sodium and potassium currents, outwardly rectifying chloride channel and large conductance Ca(2+)-activated potassium channel currents. Approximately, 95% of healthy cells allowed the formation of giga-ohm seals.

Animals↗
PubMed2004

Role of Toll-like receptor 4 in endotoxin-induced acute renal failure.

Toll-like receptor 4 (TLR4) is present on monocytes and other cell types, and mediates inflammatory events such as the release of TNF after exposure to LPS. C3H/HeJ mice are resistant to LPS-induced mortality, due to a naturally occurring mutation in TLR4. We therefore hypothesized that LPS-induced acute renal failure (ARF) requires systemic TNF release triggered by LPS acting on extrarenal TLR4. We injected C3H/HeJ mice and C3H/HeOuJ controls with 0.25 mg of LPS, and sacrificed them 6 h later for analysis of blood urea nitrogen (BUN) and kidney tissue (n = 8 per group). In contrast to C3H/HeOuJ controls, C3H/HeJ mice were completely resistant to LPS-induced ARF (6-h BUN of 32.3 +/- 1.1 vs 61.7 +/- 5.6 mg/dl). C3H/HeJ mice released no TNF into the circulation at 2 h (0.00 vs 1.24 +/- 0.16 ng/ml), had less renal neutrophil infiltration (6.4 +/- 1.0 vs 11.4 +/- 1.3 neutrophils per high power field), and less renal apoptosis, as assessed by DNA laddering. Transplant studies showed that C3H/HeJ recipients of wild-type kidneys (n = 9) were protected from LPS-induced ARF, while wild-type recipients of C3H/HeJ kidneys (n = 11) developed severe LPS-induced ARF (24-h BUN 44.0 +/- 4.1 vs 112.1 +/- 20.0 mg/dl). These experiments support our hypothesis that LPS acts on extrarenal TLR4, thereby leading to systemic TNF release and subsequent ARF. Renal neutrophil infiltration and renal cell apoptosis are potential mechanisms by which endotoxemia leads to functional ARF.

ADP-Ribosylation Factor 6↗
PubMed2004

The mouse FKBP23 binds to BiP in ER and the binding of C-terminal domain is interrelated with Ca2+ concentration.

FK506 binding protein 23 from mouse (mFKBP23) is a peptidyl-prolyl cis-trans isomerase (PPIase) from the endoplasmic reticulum (ER), which consists of an N-terminal PPIase domain and a C-terminal domain with Ca(2+) binding sites. The assay of adsorption from ER extract with glutathione S-transferase-mFKBP23 attached to glutathione-Sepharose 4B shows that mFKBP23 binds to mouse immunoglobulin binding protein (mBiP). The same assay with the recombinant proteins of the N- and C-termini of mFKBP23 shows that the binding of the C-terminus is Ca(2+)-dependent and the switch point is between 2 and 3 mM. By high concentration of Ca(2+) this binding cannot be detected. Furthermore, the Ca(2+)-regulated binding of mFKBP23 and mBiP in ER can be detected by means of co-immunoprecipitation.

Animals↗