Biomedical subjects

Y Zhu

Publications and source records attributed to Y Zhu.

At least 55 records · Page 3Linked to original sources

PubMed2004

Intensity-modulated radiation therapy for children with intraocular retinoblastoma: potential sparing of the bony orbit.

AIMS: We have evaluated the potential for intensity-modulated radiation therapy (IMRT) to reduce dose to surrounding normal tissues in children with retinoblastoma confined to the globe of the eye. MATERIALS AND METHODS: Treatment planning computed tomography (CT) scans from five children were used for comparison of four radiotherapy techniques to treat the eye. IMRT, conformal, anterior-lateral photon and en face electron plans were generated using the Corvus (NOMOS) and PLUNC treatment planning systems. Doses to surrounding critical structures were compared after normalisation of target coverage. RESULTS: The IMRT treatment technique allowed the greatest sparing of the surrounding bony orbit, with an average of 60% of the ipsilateral bony orbit treated above 20 Gy and 48% treated above 24 Gy when 45 Gy is prescribed to the globe. IMRT techniques reduced dose to the surrounding bony orbit by more than one-third compared with anterior-lateral photon and electron techniques, and by 23% compared with conformal techniques. The application of IMRT also reduced dose to other surrounding normal tissues, including the temporal lobe and contralateral orbit. CONCLUSION: IMRT shows potential for protecting normal tissues in patients requiring external beam radiation therapy for retinoblastoma.

Child↗

PubMed2004

Risk factors and clinical outcomes of nosocomial multi-drug resistant Pseudomonas aeruginosa infections.

Risk factors for multi-drug resistant Pseudomonas aeruginosa (MDRP) infections were investigated using a case-control study design involving MDRP patients (N = 44) and controls (N = 68). A retrospective cohort study was performed to study the predictive factors of clinical outcome in MDRP patients. Multivariate analysis demonstrated that previous exposure to imipenem/meropenem [odds ratio (OR), 44.8] and mechanical ventilation (OR 8.2) were risk factors for nosocomial infections of MDRP. Of 44 cases of MDRP infections, 20 patients died directly from P. aeruginosa infections. Pulsed-field gel electrophoresis (PFGE) analysis on serial isolates from three patients showed that profiles of isolates from the same patient were closely related or indistinguishable. Multivariate analysis demonstrated that patients with adverse clinical outcomes were more likely to have been treated with mechanical ventilation (OR 12.8), and more likely to have MDRP resistance patterns that did not change during treatments (OR 26.5). We concluded that mechanical ventilation and previous exposure to imipenem/meropenem were independent risk factors for MDRP infections, while mechanical ventilation and antibiotic resistance switch were predictive factors of outcomes of MDRP infections.

Adult↗

PubMed2004

Serum levels of type IIA procollagen amino terminal propeptide (PIIANP) are decreased in patients with knee osteoarthritis and rheumatoid arthritis.

OBJECTIVE: The aim of this study was to develop a specific immunoassay for PIIANP and measure its serum concentration in healthy controls and in patients with osteoarthritis (OA) and rheumatoid arthritis (RA). In addition, we investigated circulating forms recognized by antiserum IIA in pools of serum from healthy adults, patients with OA and patients with RA. DESIGN: Using as immunogen and standard the recombinant human Glutathione S-Transferase (GST)-exon 2 fusion protein of type II collagen, we developed a competitive polyclonal antibody-based ELISA. We compare serum PIIANP levels in 43 patients with knee OA (23 women and 20 men; mean age: 62.6+/-9.6 yr), 63 women with RA (mean age: 54+/-16 yr) and 88 healthy controls (67 women, mean age: 53+/-13 yr and 21 men, mean age: 63+/-7 yr). We randomly selected serum in each group for analyze circulating forms. RESULTS: The immunoassay we developed demonstrated adequate intra and inter-assay precision (CV<10%) and dilution recovery (mean: 96%), allowing accurate measurements of serum PIIANP from 1.13 to 40 ng/ml. No significant cross-reactivity of the ELISA was observed with purified intact human procollagen type I N-propeptide, circulating thrombospondin and von Willebrand factor, proteins which exhibit significant sequence homology with PIIANP. Western blot analysis showed that antiserum IIA recognized two circulating immunoreactive forms of approximately 80 and 100 KDa respectively in serum from healthy adults, patients with OA and RA but also in a pool of synovial fluids from patients with OA. Serum PIIANP levels were markedly decreased in patients with knee OA (12.0+/-3.2 vs 25.8+/-7.5 ng/ml for OA and controls respectively, P<0.0001) and RA (14.1+/-2.5 ng/ml vs 21.7+/-7.6 ng/ml for RA and controls respectively, P<0.0001). In patients with RA, serum PIIANP levels were higher in those taking low-dose prednisone compared to non-users (15.0+/-2.4 vs 13.5+/-2.4 ng/ml, P<0.05). CONCLUSIONS: We have developed the first specific immunoassay for serum PIIANP which exhibits adequate technical performances. This assay detects specifically two immunoreactive forms both in healthy adults and patients with arthritis and does not cross react with other proteins with sequence homology with PIIANP. Levels of PIIANP were significantly decreased in patients with knee OA and RA suggesting that type IIA collagen synthesis may be altered in these arthritic diseases. The measurement of type IIA collagen synthesis with this new molecular marker may be useful for the clinical investigation of patients with joint diseases.

Adult↗

PubMed2004

Structural properties and charge ordered states in RMnO3 (R=La, Pr, Nd, Ca, Sr) and (La, Sr)2NiO4.

Structural distortions arising from the condensations of two essential kinds of phonon modes: the triply degenerate rotational modes (phix, phiy, phiz) of MnO(6) and the doubly degenerate Jahn-Teller active modes (Q1, Q2) have been systematically investigated in the perovskite manganites. Microstructural features associated with certain types of distortions have been observed by transmission electron microscopy (TEM). In RMnO(3) and La(Sr)(2)NiO(4), we characterize the local structure, charge ordered states and orbital ordering by means of low-temperature TEM. We present direct evidence that the stripe modulation in La(Sr)(2)NiO(4) is indeed one-dimensional within each NiO(2) plane. Several typical kinds of defect structures, including antiphase boundaries and the 90 degrees -twin domains, appear commonly in the charge-ordered states.

Journal Article↗

PubMed2004

Neuroprotection by transforming growth factor-beta1 involves activation of nuclear factor-kappaB through phosphatidylinositol-3-OH kinase/Akt and mitogen-activated protein kinase-extracellular-signal regulated kinase1,2 signaling pathways.

Prevention of neuronal apoptosis has been introduced as a new therapeutic strategy for neurodegenerative disorders. We have previously reported anti-apoptotic effects of transforming growth factor-beta1 (TGF-beta1), a multifunctional cytokine, in models of cerebral ischemia and in cultured neurons and recently focused on the mechanisms underlying the anti-apoptotic effect of TGF-beta1. The anti-apoptotic transcriptional factor nuclear factor kappa B (NF-kappaB) shows high impact in the cell survival function of multiple cytokines and growth factors. The present study explored whether NF-kappabeta is a target of TGF-beta1 and which signaling pathways involved in the activation of NF-kappabeta are triggered by TGF-beta1. We demonstrated that TGF-beta1 increased the transcriptional activity of NF-kappabeta in cultured hippocampal neurons in a time- and concentration-dependent manner. Furthermore, TGF-beta1 induced translocation of p65/NF-kappabeta to the nucleus and enhanced NF-kappabeta transcriptional activity in the presence of apoptotic stimuli. TGF-beta1-mediated NF-kappabeta activation was blocked by wortmannin and U0126, indicating the involvement of both phosphatidylinositol-3-OH kinase (PI3k)/Akt and mitogen-activated protein kinase (MAPK)/extracellular-signal regulated kinase (Erk)1,2 pathways in the action of TGF-beta1. TGF-beta1 produced a concomitant increase in the phosphorylations of Ikappabeta kinase (IKKalpha/beta) and Ikappabetaalpha with a subsequent degradation of Ikappabetaalpha. Interestingly, the increased phosphorylation of IKKalpha/beta and Ikappabetaalpha was abrogated by wortmannin, but not by U0126, suggesting that PI3k/Akt and MAPK/Erk1,2 pathways triggered by TGF-beta1 regulated the activation of NF-kappabeta through different mechanisms. Of note, wortmannin and U0126, as well as kappabeta-decoy DNA, abolished the anti-apoptotic effect of TGF-beta1, corroborating the notion that both PI3k/Akt and MAPK/Erk1,2 pathways, and NF-kappabeta activity are necessary for the anti-apoptotic activity of TGF-beta1.

Animals↗

PubMed2004

Ca(2+)-calmodulin signalling pathway up-regulates GABA synaptic transmission through cytoskeleton-mediated mechanisms.

We investigated the role of calcium (Ca(2+))/calmodulin (CaM) signaling pathways in modulating GABA synaptic transmission at CA1 pyramidal neurons in hippocampal slices. Whole-cell pipettes were used to record type A GABA receptor (GABA(A)R)-gated inhibitory postsynaptic currents (IPSCs) and to perfuse intracellularly modulators in the presence of glutamate receptor antagonists. GABA(A)R-gated IPSCs were enhanced by the postsynaptic infusions of adenophostin (1 microM), a potent agonist of inositol-1,4,5-triphosphate receptor (IP(3)R) that induces Ca(2+) release. The enhancement was blocked by co-infusing either 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (10 mM) or CaM-binding peptide (100 microM). Moreover, the postsynaptic infusion of Ca(2+)-CaM (40/10 microM) enhanced both evoked and spontaneous GABA(A)R-gated IPSCs. The enhancement was attenuated by co-infusing 100 microM CaM-KII(281-301), an autoinhibitory peptide of CaM-dependent protein kinases. These results indicate that postsynaptic Ca(2+)-CaM signaling pathways essentially enhance GABAergic synaptic transmission. In the investigation of synaptic targets for the enhancement, we found that IP(3)R agonist-enhanced GABA(A)R-gated IPSCs were attenuated by co-infusing colchicine (30 microM), vincristine (3 microM) or cytochalasin D (1 microM) that inhibits tubulin or actin polymerization, implying that actin filament and microtubules are involved. We conclude that postsynaptic Ca(2+)-CaM signaling pathways strengthen the function of GABAergic synapses via a cytoskeleton-mediated mechanism, probably the recruitment of receptors in the postsynaptic membrane.

Animals↗

PubMed2004

Expression of TRAIL, DR4, and DR5 in kidney and serum from patients receiving renal transplantation.

Renal transplantation is the best treatment of some end-stage renal diseases. Unfortunately, not every transplant is successful due to the rejection or dysfunction of the transplanted kidney. Many cytokines participate in rejection by inducing inflammation or apoptosis. In this study, the expressions of TRAIL, DR4, and DR5 in rejected renal tissue and of serum soluble TRAIL (sTRAIL) in patients with kidney rejection were investigated by immunohistochemical staining and sandwich enzyme-linked immunosorbent assay, respectively. The results showed that the expression of TRAIL, DR4 and DR5, and serum sTRAIL levels were markedly upregulated among renal transplant patients. Since both membrane and soluble forms of TRAIL can induce apoptosis of DR4/DR5-expressing cells via recruiting FADD and caspase 8, elevated TRAIL and its receptors may participate in renal graft rejection.

Apoptosis↗

PubMed2004

A unique determination of boundary condition in quantitative electron diffraction: Application to accurate measurements of mean inner potentials.

We combine off-axis electron holography and electron shadow imaging to accurately determine the specimen thickness and the incident electron beam direction over the illuminated area of a crystal. We, furthermore, quantify the variations in diffraction intensity with position over the same area. This unique solution to the experimental boundary condition problem enables us to make precise measurements of mean inner electrostatic potentials and structure factors that are sensitive to the bonding characteristics of materials. In this paper, we present the results of mean-inner potential determination from silicon and the newly discovered magnesiumdiboride superconductor.

Journal Article↗

PubMed2004

Lorentz phase microscopy of magnetic materials.

We propose a method of Lorentz phase microscopy for in situ studies and imaging magnetic materials in transmission electron microscopy (TEM) based on the solution of the magnetic transport-of-intensity equation. We also describe the appropriate way of solving this equation that may be useful for understanding and practical use of non-holographic methods for phase retrieval in electron microscopy, especially in imaging magnetic materials. The method is simple, since it is primarily based on classical Fresnel imaging. On the other hand, it is quantitative and can be applied in any TEM without changing the basic hardware. Therefore, it may well find important practical applications in ultramicroscopy and modern magnetic materials research.

Journal Article↗

PubMed2004

On the transport of intensity technique for phase retrieval.

The Transport of Intensity technique is becoming a viable alternative to electron holography for phase retrieval in Transmission Electron Microscopy. However, several issues are still to be clarified in order to ascertain the applicability of the technique; among them, the controversy regarding its geometrical or wave-optical nature, as related to the phase detection limit. We show here that the Transport of Intensity is a wave-optical technique that works in a special regime of small defocus where the image intensity is linear with the defocus parameter. By a simple analytical example we show that the Transport of Intensity correctly reconstructs the electron optical phase shift even when the phase is smaller than pi, a value defining the boundary between the geometrical and wave approaches. Another example is given, the reconstruction of a phase jump, accompanied with experimental support showing that phase retrieval by Electron Holography and Transport of Intensity techniques yields results in good agreement.

Algorithms↗

PubMed2004

A statistical model for functional mapping of quantitative trait loci regulating drug response.

Differential drug response, that is, pharmacodynamics, is most often likely to be a complex trait, controlled by the combined influences of multiple genes and environmental influences. Genetic mapping has proven to be a powerful tool for detecting and identifying specific genes affecting complex traits, that is, quantitative trait loci (QTL), based on polymorphic markers. In this article, we present a novel statistical model for genetic mapping of QTL governing pharmacodynamic processes. In principle, this model is a combination of functional mapping proposed to map function-valued traits and linkage disequilibrium mapping designed to provide high-resolution mapping of QTL by making use of recombination events created at a historic time. We implement a closed-form solution for the Expectation-Maximization algorithm to estimate the population genetic parameters of QTL and the simplex algorithm to estimate the curve parameters describing the pharmacodynamic changes of different QTL genotypes in response to drug dose or concentrations. Extensive simulations are performed to investigate the statistical properties of our model. The implications of our model in pharmacogenetic and pharmacogenomic research are discussed.

Algorithms↗

PubMed2004

Stage-specific expression of leukaemia inhibitory factor and its receptor in rabbit pre-implantation embryo and uterine epithelium during early pregnancy.

Leukaemia inhibitory factor (LIF) has been shown to play an important role in the development and implantation of blastocysts in mice. In the current study, the reverse transcription-polymerase chain reaction (RT-PCR) was employed to examine the expression patterns of LIF and its receptor (LIFR) genes in rabbit embryos during pre-implantation development, and the uterine expression of LIF and LIFR was also evaluated by Western blotting. Transcripts for LIFR were detected within morula and blastocyst-stage embryos, while the LIF mRNA was only found in blastocysts (from early to fully expanded blastocoel cavities), indicating that embryo-derived LIF can act in an autocrine manner on the process of blastocyst formation. The expression levels of LIF and LIFR in uterine epithelium were gradually increased during pre-implantation period and reached their highest levels on days 6.5 of pregnancy, just before the time of blastocyst implantation, suggest that paracrine LIF circuit should exist between the endometrium and the early embryos, which may be involved in the embryo-maternal dialogue and important for the blastocyst implantation. The data present here show the stage-specific and dynamic expression patterns of LIF and LIFR, both in embryos and endometrium, during early pregnancy in rabbits, which indicated that LIF might play an important role in the pre-implantation development and subsequent implantation of rabbit embryos.

Animals↗

PubMed2004

Linkage disequilibrium and haplotype architecture for two ABC transporter genes (ABCC1 and ABCG2) in Chinese population: implications for pharmacogenomic association studies.

Information about linkage disequilibrium (LD) patterns and haplotype structures for candidate genes is instructive for the design and analysis of genetic association studies for complex diseases and drug response. ABCC1 and ABCG2 are genes coding for two multidrug resistance (MDR) associated transporters; they are also related to some pathophysiological traits. To pinpoint the LD profiles of these MDR genes in Chinese, we systemically screened 27 unrelated individuals for single nucleotide polymorphisms (SNPs) in the coding and regulatory regions of these genes, and thereby characterized their haplotype structures. Despite marked variations in haplotype diversity, LD pattern and intragenic recombination intensity between the two genes, both loci could be partitioned into several LD blocks, in which a modest number of haplotypes accounted for a high fraction of the sampled chromosomes. We concluded that each locus has its own genomic LD profile, but that they still share a common segmental LD architecture with low haplotype diversity. Our data will benefit genetic association studies of complex traits and drug response possibly related to these genes.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2004

Ion channels in interstitial cells of Cajal as targets for neurotransmitter action.

Interstitial cells of Cajal (ICC) are involved in generation of gut pacemaker activity, neurotransmission and stretch sensation. Pacemaker ICC exhibit spontaneous cyclic calcium oscillations that are in synchrony with its pacemaker activity. The spontaneous rhythmic inward currents in ICC that underlie gut pacemaker activity are linked to this calcium oscillation. It is probable that more than one type of channel contributes to the inward current with a high conductance chloride channel and a nonselective cation channel being the main candidates. The activation of these channels is linked to intracellular calcium cycling mechanism and involves inositol 1,4,5-trisphosphate (IP3)-mediated calcium release from the sarcoplasmic reticulum, and calcium uptake into mitochondria. This ion channel activity is modulated by signalling through neurotransmitter receptors, including the NK1 receptor. This finding and the presence of other neurotransmitter receptor mRNA transcripts indicates that ion channels in ICC are targets for neurotransmitter action. The ether-a-go-go-related (ERG) K channel is probably the most important K channel contributing to the resting membrane potential and excitability of the ICC. Many ion channels in ICC are regulated by second messenger systems which makes them highly susceptible to neurotransmitter modulation.

Animals↗

PubMed2003

Phase imaging and nanoscale currents in phase objects imaged with fast electrons.

We derive the magnetic transport-of-intensity equation (MTIE) that links defocused contrast of magnetic nanoobjects imaged by partially coherent electron waves to their micromagnetic parameters. This provides Maxwell's explanation for observable contrast in terms of the Z component of currents existing around vortices in superconductors and domain vortices and walls in ferromagnets. The solution of the MTIE via Fourier transform is used for quantitative mapping of magnetic flux and projected induction in magnetic and superconducting materials imaged by Lorentz microscopy.

Journal Article↗

PubMed2003

Effect of planting covers on herbicide persistence in landscape soils.

Recent monitoring shows that the majority of urban streams in the United States are contaminated by pesticide residues, and the contamination is mainly due to runoff from residential landscapes. In this study we evaluated the effect of landscape planting on persistence of the herbicides 2,4-D and dicamba in soil under laboratory conditions. The herbicides exhibited substantially different persistence in the same soil type that had been subjected to different planting practices for about 6 years. In the 0-10 cm surface layer, the half-life of 2,4-D was 30.7 d in soil under trees, which was about 20 times longer than in soil planted with turf grass (1.6 d). The difference in 2,4-D persistence was closely correlated to the number of 2,4-D-degrading bacteria that had evolved in the soils. The half-life of dicamba was much longer in soil under a tree canopy (149 d) than in mulched soil (7.9 d). The rate of dicamba degradation was proportional to soil organic matter content. This study indicates that planting practices can modify soil chemical properties and microbial activity and may further affect pesticide runoff potential by influencing pesticide degradation. Characterizing pesticide behavior as a function of planting covers may improve our understanding of pesticide runoff in urban environments and also help to identify strategies for minimizing pesticide contamination to urban streams.

2,4-Dichlorophenoxyacetic Acid↗

PubMed2003

Identification by subtractive suppression hybridization of bacteria-induced genes expressed in Manduca sexta fat body.

Insect immune processes are mediated by programs of differential gene expression. To understand the molecular regulation of the immune response in the tobacco hornworm, Manduca sexta, the relevant subset of differentially expressed genes of interest must be identified, cloned and studied in detail. In this study, suppression subtractive hybridization, a PCR-based method for cDNA subtraction was performed to identify mRNAs from fat body of immunized larvae that are not present (or present at a low level) in control larvae. A subtracted cDNA library enriched in immune-inducible genes was constructed. Northern blot analysis of a sample of clones from our subtracted library indicated that >90% of the clones randomly selected from the subtracted library are immune inducible. Sequence analysis of 238 expressed sequence tags (ESTs) revealed that 120 ESTs, representing 54 distinct genes or gene families, had sequences identical or similar to previously characterized genes, some of which have been confirmed to be involved in innate immunity. These ESTs were categorized into seven groups, including pattern recognition proteins, serine proteinases and their inhibitors, and antimicrobial proteins. 112 ESTs, about 47.5% of the library, showed no significant similarity to any known genes. The sequences identified in this M. sexta library reflect our knowledge of insect immune strategies and may facilitate better understanding of insect immune responses.

Adipose Tissue↗

PubMed2003

Upregulation of survivin by HIV-1 Vpr.

The human survivin gene belongs to the family of inhibitor of apoptosis proteins (IAP) and is involved in apoptosis inhibition and regulation of cell division. The survivin gene is the only member of the IAP family whose expression is known to be regulated through the cell cycle. Survivin expression reaches the highest levels during the G(2)/M transition and then is rapidly degraded during the G(1) phase. Here we report that the human immunodeficiency virus type 1 (HIV-1) upregulates Survivin expression via survivin promoter transactivation. Vpr, an HIV-1 accessory protein that induces cell cycle arrest in G(2)/M, is necessary and sufficient for this effect. Blocking Vpr-induced G(2)/M arrest leads to elimination of the survivin promoter transactivation by Vpr. Our results suggest that Survivin may be actively involved in regulating cell viability during HIV-1 infection.

Blotting, Western↗