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Biomedical subjects

Z Xu

Publications and source records attributed to Z Xu.

At least 91 records · Page 5Linked to original sources
PubMed2001

Synthetic superoxide dismutase/catalase mimetics reduce oxidative stress and prolong survival in a mouse amyotrophic lateral sclerosis model.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that causes motoneuron degeneration, paralysis and death. Mutations in Cu, Zn superoxide dismutase (SOD1) are one cause of this disease. It is widely suspected that increased reactive oxidative species (ROS) is involved in motoneuron degeneration but whether such an involvement plays a role in ALS progression in vivo is uncertain. We treated mice expressing human mutant SOD1 G93A with EUK-8 and EUK-134, two synthetic SOD/catalase mimetics that have shown efficacy in several animal models of human diseases. These treatments reduced levels of oxidative stress and prolonged survival. The results suggest that oxidative stress plays an active role in ALS and illustrate the potential for treatment strategies aimed specifically against ROS.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Protein kinase PKR is required for platelet-derived growth factor signaling of c-fos gene expression via Erks and Stat3.

The double-stranded RNA (dsRNA)-activated protein kinase PKR is an interferon (IFN)-induced enzyme that controls protein synthesis through phosphorylation of eukaryotic initiation factor 2alpha (eIF-2alpha). PKR also regulates signals initiated by diverse stimuli, including dsRNA, IFN-gamma, tumor necrosis factor-alpha, interleukin-1 and lipopolysaccharide, to different transcription factors, resulting in pro-inflammatory gene expression. Stat3 plays an essential role in promoting cell survival and proliferation by different growth factors, including platelet-derived growth factor (PDGF). Here we show that PKR physically interacts with Stat3 and is required for PDGF-induced phosphorylation of Stat3 at Tyr705 and Ser727, resulting in DNA binding and transcriptional activation. PKR-mediated phosphorylation of Stat3 on Ser727 is indirect and channeled through ERKS: Although PKR is pre-associated with the PDGF beta-receptor, treatment with PDGF only modestly activates PKR. However, the induction of c-fos by PDGF is defective in PKR-null cells. Taken together, these results establish PKR as an upstream regulator of activation of Stat3 and as a common mediator of both growth-promoting and growth-inhibitory signals.

Animals↗
PubMed2001

Study of tau decays to six pions and a neutrino.

The tau decays to six-pion final states have been studied with the CLEO detector at the Cornell Electron Storage Ring. The measured branching fractions are B(tau(-)-->2pi(-)pi(+)3pi(0)nu(tau)) = (2.2+/-0.3+/-0.4)x10(-4) and B(tau(-)-->3pi(-)2pi(+)pi(0)nu(tau)) = (1.7+/-0.2+/-0.2)x10(-4). A search for substructure in these decays shows that they are saturated by intermediate states with eta or omega mesons. We present the first observation of the decay tau(-)-->2pi(-)pi(+)omega(nu)tau and the branching fraction is measured to be (1.2+/-0.2+/-0.1)x10(-4). The measured branching fractions are in good agreement with the isospin expectations but somewhat below the conserved-vector-current predictions.

Journal Article↗
PubMed2001

Observation of new states decaying into Lambda+(c)pi(-)pi(+).

Using 13.7 fb(-1) of data recorded by the CLEO detector at the Cornell Electron Storage Ring, we investigate the spectrum of charmed baryons which decay into Lambda+(c)pi(-)pi(+) and are more massive than the Lambda+(c)(2625) baryon. We find evidence for two new states: one is broad and has an invariant mass roughly 480 MeV above that of the Lambda+(c) baryon; the other is narrow with an invariant mass of 596+/-1+/-2 MeV above the Lambda+(c) mass.

Journal Article↗
PubMed2001

Evidence of New States Decaying into Xi(*)(c)pi.

Using 13.7 fb(-1) of data recorded by the CLEO detector at Cornell Electron Storage Ring, we report evidence of two new charmed baryons: one decaying into Xi(0')(c)pi(+) with the subsequent decay Xi(0')(c)-->Xi(0)(c)gamma, and its isospin partner decaying into Xi(+')(c)pi(-) followed by Xi(+')(c)-->Xi(+)(c)gamma. We measure the following mass differences for the two states: M(Xi(0)(c)gammapi(+))-M(Xi(0)(c)) = 318.2+/-1.3+/-2.9 MeV and M(Xi(+)(c)gammapi(-))-M(Xi(+)(c)) = 324.0+/-1.3+/-3.0 MeV. We interpret these new states as the J(P) = 1 / 2(-) Xi(c1) particles, the charmed-strange analogs of the Lambda(+)(c1)(2593).

Journal Article↗
PubMed2001

Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family.

CEP-1347 (KT7515) promotes neuronal survival at dosages that inhibit activation of the c-Jun amino-terminal kinases (JNKs) in primary embryonic cultures and differentiated PC12 cells after trophic withdrawal and in mice treated with 1-methyl-4-phenyl tetrahydropyridine. In an effort to identify molecular target(s) of CEP-1347 in the JNK cascade, JNK1 and known upstream regulators of JNK1 were co-expressed in Cos-7 cells to determine whether CEP-1347 could modulate JNK1 activation. CEP-1347 blocked JNK1 activation induced by members of the mixed lineage kinase (MLK) family (MLK3, MLK2, MLK1, dual leucine zipper kinase, and leucine zipper kinase). The response was selective because CEP-1347 did not inhibit JNK1 activation in cells induced by kinases independent of the MLK cascade. CEP-1347 inhibition of recombinant MLK members in vitro was competitive with ATP, resulting in IC(50) values ranging from 23 to 51 nm, comparable to inhibitory potencies observed in intact cells. In addition, overexpression of MLK3 led to death in Chinese hamster ovary cells, and CEP-1347 blocked this death at doses comparable to those that inhibited MLK3 kinase activity. These results identify MLKs as targets of CEP-1347 in the JNK signaling cascade and demonstrate that CEP-1347 can block MLK-induced cell death.

Animals↗
PubMed2001

Observation of the Omega(0)(c) Charmed Baryon at CLEO.

The CLEO experiment at the CESR collider has used 13.7 fb(-1) of data to search for the production of the Omega(0)(c) (css ground state) in e(+)e(-) collisions at square root of (s) approximately 10.6 GeV. The modes used to study the Omega(0)(c) are Omega(-)pi(+), Omega(-)pi(+)pi(0), Xi-K-pi(+)pi(+), Xi0K-pi(+), and Omega(-)pi(+)pi(+)pi(-). We observe a signal of 40.4+/-9.0(stat) events at a mass of 2694.6+/-2.6(stat)+/-1.9(syst) MeV/c(2), for all modes combined.

Journal Article↗
PubMed2001

Regulation of subcellular localization of alpha1-adrenoceptor subtypes.

Alpha1-adrenergic receptors (AR) are members of the superfamily of G protein-coupled receptors (GPCRs) which mediate the effects of the sympathetic nervous system. Alpha1-AR comprise a heterogeneous family of three distinct isoforms of alpha1A, alpha1B and alpha1D; however, very little is known about their difference in physiological role or regulation. We have recently observed a subtype-specific differences in subcellular localization of alpha1-ARs; thus, alpha1A-AR predominantly localize intracellularly, while alpha1B-AR on the cell surface. To examine the molecular mechanism for the subtype-specific differences in subcellular localization, we conducted a search for novel proteins that interact with the alpha1B-AR, specifically focusing on the carboxyl-terminal cytoplasmic domain. Using interaction cloning and biochemical techniques, we demonstrate that gC1q-R interacts with alpha1B-AR in vitro and in vivo through the specific site, and that in cells which co-express alpha1B-AR and gC1q-R, the subcellular localization of alpha1B-AR is markedly altered and its expression is down-regulated. These results suggest that gC1q-R plays a role in the regulation of the subcellular localization as well as the function of alpha1B-ARs.

Animals↗
PubMed2001

The expression of calcitonin gene-related peptide in dorsal horn neurons of the mouse lumbar spinal cord.

Using immunohistochemistry and in situ hybridization the expression of calcitonin gene-related peptide (CGRP) was studied in the mouse spinal cord under normal conditions and after unilateral rhizotomy and after local colchicine treatment. Under normal conditions a dense plexus of CGRP-immunoreactive (IR) fibres was observed in the superfical layers of dorsal horns with lower numbers of fibers in deeper laminae. Seven days after unilateral rhizotomy, there was a marked reduction of CGRP-IR fibres in the ipsilateral superfical layers and distinctly CGRP-IR neurons could be detected in the ipsilateral lamina III. CGRP mRNA-positive neurons were observed in lamina III in both the ipsilateral and contralateral dorsal horn. Colchicine treatment did not markedly increase the number of CGRP-IR neurons. The results suggest that CGRP is synthesized in local dorsal horn neurons of the mouse, and these neurons presumably participate in sensory processing.

Animals↗
PubMed2001

First observation of the decays B(0) --> D(*-)p_p pi+ and B(0) --> D(*-)p_n.

We report the first observation of exclusive decays of the type B-->D(*)N_NX, where N is a nucleon. Using a sample of 9.7x10(6)B_B pairs collected with the CLEO detector operating at the Cornell Electron Storage Ring, we measure the branching fractions B(B0-->D(*-)p_p pi(+)) = (6.5(+1.3)(-1.2)+/-1.0)x10(-4) and B(B0-->D(*-)p_n) = (14.5(+3.4)(-3.0)+/-2.7)x10(-4). Antineutrons are identified by their annihilation in the CsI electromagnetic calorimeter.

Journal Article↗
PubMed2001

Intracerebroventricular carbachol induces FOS immunoreactivity in lamina terminalis neurons projecting to the supraoptic nucleus.

Central application of the non-selective cholinergic receptor agonist, carbachol, induces water intake, vasopressin (VP) release and an acute increase in arterial blood pressure. Forebrain sites, particularly those located along the lamina terminalis (LT) (i.e. the subfornical organ (SFO), organum vasculosum (OV) and the median preoptic nucleus (MePO)) and in the hypothalamus, have been proposed as the major targets for producing the effects induced by intracerebroventricular (i.c.v.) carbachol injections. However, the functional and neuroanatomical relationship among carbachol-activated cells along the LT and hypothalamic areas such as the supraoptic nuclei (SON), is unclear. The present study investigated the i.c.v. carbachol-induced activity of the soma of LT projections which descend from the SFO, OV and MePO and terminate in the region of the SON. Cells along the LT were retrogradely labeled from SON-targeted injections of fluoro-gold, and FOS-immunoreactivity (FOS-ir) was used to assess activation. A significant number of cells in the SFO, OV and MePO were double-labeled for both FOS-ir and fluoro-gold. The FOS labeling in the cells of the LT-associated structures was significantly reduced by pretreatment with the i.c.v. muscarinic antagonist, atropine. Taken together, the results indicate that neurons located in structures located along the LT and projecting to the region of the SON are activated by i.c.v. carbachol and that these receptors are likely to be muscarinic.

Animals↗
PubMed2001

Measurement of the lambda(+)(c) lifetime.

The Lambda+c lifetime is measured using 9.0 fb(-1) of e+e- annihilation data collected on or just below the Upsilon(4S) resonance with the CLEO II.V detector at CESR. Using an unbinned maximum likelihood fit, the Lambda+c lifetime is measured to be 179.6+/-6.9(stat)+/-4.4(syst) fs. The precision of this colliding beam measurement is comparable to other measurements, which are based on fixed-target experiments, with different systematic uncertainties.

Journal Article↗
PubMed2001

First observation of the sigma(*+)(c) baryon and a new measurement of the sigma(*+)(c) mass.

Using data recorded with the CLEO II and CLEO II.V detector configurations at the Cornell Electron Storage Rings, we report the first observation and mass measurement of the Sigma(*+)(c) charmed baryon, and an updated measurement of the mass of the Sigma(+)(c) baryon. We find M(Sigma(*+)(c))-M(Lambda(+)(c)) = (231.0+/-1.1+/-2.0) MeV, and M(Sigma(+)(c))-M(Lambda(+)(c)) = (166.4+/-0.2+/-0.3) MeV, where the errors are statistical and systematic, respectively.

Journal Article↗
PubMed2001

Bound ro-vibronic states of triplet H3(+).

On the basis of a new, highly accurate potential energy hypersurface for the lowest triplet state of H+3, (3)Sigma(+)(u), the bound ro-vibronic states are calculated for J</=5. Since the potential has very shallow minima, those states exist only up to single vibrational excitation. The symmetry properties of the ro-vibrational states are investigated. Further, it is demonstrated that the first excited triplet state, which intersects conically with the (3)Sigma(+)(u) state, has no effect on the reported ro-vibrational energies.

Journal Article↗
PubMed2001

Expression sequence tag-specific full-length cDNA cloning: actin cDNAs.

Current strategies for cDNA cloning are based on construction of cDNA libraries and colony screening. The process of obtaining a full-length cDNA clone can be highly time and labor intensive. Using the human actin gene as a model target cDNA, we have developed an RNA-capture method for rapid cloning of full-length cDNAs. The approach involves the capture of mRNA with expressed sequence tag (EST)-derived, biotin labeled antisense "capture" primers and streptavidin-coated magnetic beads. Full-length cDNA is then synthesized from purified EST-specific mRNA and cloned directly into plasmid vectors. The results of using beta-actin-based capture primers on cytoplasmic RNA were the isolation of both beta- and gamma-actin cDNA clones. Of the 16 actin-specific cDNA clones analyzed, 15 (93%) were full-length. This approach for cloning full-length cDNAs from available ESTs or partial cDNA sequences will facilitate a more rapid and efficient characterization of gene structure and function.

Actins↗
PubMed2001

Study of B Decays to Charmonium States: B-->eta(c)K and B --> chi(c0)K.

In a sample of 9.66x10(6)B&Bmacr; pairs collected with the CLEO detector we make the first observation of B decays to an eta(c) and a kaon. We measure branching fractions B(B+-->eta(c)K+) = (0.69(+0.26)(-0.21)+/-0.08+/-0.20)x10(-3) and B(B degrees -->eta(c)K degrees ) = (1.09(+0.55)(-0.42)+/-0.12+/-0.31)x10(-3), where the first error is statistical, the second is systematic, and the third is from the eta(c) branching fraction uncertainty. From these we extract the eta(c) decay constant in the factorization approximation, f(eta(c)) = 335+/-75 MeV. We also search for B decays to a chi(c0) and a kaon. No evidence for a signal is found and we set 90% C.L. upper limits: B(B+-->chi(c0)K+)<4.8x10(-4) and B(B degrees -->chi(c0)K degrees )<5.0x10(-4).

Journal Article↗
PubMed2001

Calculation of dose distribution near an innovative concentric balloon catheter for endovascular brachytherapy.

Purpose: Using a radioactive solution-filled catheter for intravascular irradiation has the potential problem of chemical and radiological toxicity in the case of a balloon rupture. In order to reduce this risk, an innovative concentric balloon catheter was developed.Methods and Materials: The concentric balloon was made by inner and outer balloons filled with saline and radioactive solution, respectively. The optimal inner radius was determined by comparing the dose rate reduction vs. the volume reduction for various inner and outer radii for 188Re, 32P, and 90Y solutions.Results: For a balloon with an outer radius of 1.5 mm, there was no advantage of a concentric balloon. For balloons with outer radii of 3.0 and 5 mm, the optimal inner radius was 1.5 and 3 mm, respectively.Conclusions: With the newly designed concentric balloon, the risk of toxicity can be reduced while keeping the dose rate high enough so that the treatment times within tolerable limits are still maintained.

Journal Article↗