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Biomedical subjects

C Xu

Publications and source records attributed to C Xu.

At least 235 records · Page 13Linked to original sources
PubMed1996

Binding domains for blockers and substrates on the cloned human dopamine transporter studied by protection against N-ethylmaleimide-induced reduction of 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)[3H]tropane ([3H]WIN 35,428) binding.

Binding sites for 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)[3H]tropane ([3H]WIN 35,428) on the human dopamine transporter expressed in C6 glioma cells were alkylated with N-ethylmaleimide (NEM), and the protective potency of the blockers cocaine, N[1-(2-benzo[b]thiophenyl) cyclohexyl]piperidine (BTCP), and benztropine, and of the substrates dopamine, d-amphetamine, and norepinephrine was measured. In general, the protective potency was lower (at least 4-5 times) than the potency in inhibiting [3H]WIN 35,428 binding with the compounds present under the same experimental conditions used for the NEM alkylation. However, the disparity was substantially greater for all substrates tested (23- to 44-fold) than for the blockers (4- to 11-fold), especially cocaine (5-fold) and BTCP (4-fold). Benztropine took an intermediate place (11-fold) between cocaine (5-fold) and BTCP (4-fold), on the one hand, and dopamine (23-fold), on the other hand. [3H]WIN 35,428 binding was best described by a one-site model under the present conditions. The results are discussed in terms of models involving blocker-induced conformational changes and overlapping nonidentical binding domains for blockers and substrates.

Animals↗
PubMed1996

Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy.

Intrinsic, three-dimensionally resolved, microscopic imaging of dynamical structures and biochemical processes in living preparations has been realized by nonlinear laser scanning fluorescence microscopy. The search for useful two-photon and three-photon excitation spectra, motivated by the emergence of nonlinear microscopy as a powerful biophysical instrument, has now discovered a virtual artist's palette of chemical indicators, fluorescent markers, and native biological fluorophores, including NADH, flavins, and green fluorescent proteins, that are applicable to living biological preparations. More than 25 two-photon excitation spectra of ultraviolet and visible absorbing molecules reveal useful cross sections, some conveniently blue-shifted, for near-infrared absorption. Measurements of three-photon fluorophore excitation spectra now define alternative windows at relatively benign wavelengths to excite deeper ultraviolet fluorophores. The inherent optical sectioning capability of nonlinear excitation provides three-dimensional resolution for imaging and avoids out-of-focus background and photodamage. Here, the measured nonlinear excitation spectra and their photophysical characteristics that empower nonlinear laser microscopy for biological imaging are described.

Animals↗
PubMed1996

Crystalline Ropes of Metallic Carbon Nanotubes

Fullerene single-wall nanotubes (SWNTs) were produced in yields of more than 70 percent by condensation of a laser-vaporized carbon-nickel-cobalt mixture at 1200degreesC. X-ray diffraction and electron microscopy showed that these SWNTs are nearly uniform in diameter and that they self-organize into "ropes," which consist of 100 to 500 SWNTs in a two-dimensional triangular lattice with a lattice constant of 17 angstroms. The x-ray form factor is consistent with that of uniformly charged cylinders 13.8 +/- 0.2 angstroms in diameter. The ropes were metallic, with a single-rope resistivity of <10(-4) ohm-centimeters at 300 kelvin. The uniformity of SWNT diameter is attributed to the efficient annealing of an initial fullerene tubelet kept open by a few metal atoms; the optimum diameter is determined by competition between the strain energy of curvature of the graphene sheet and the dangling-bond energy of the open edge, where growth occurs. These factors strongly favor the metallic (10,10) tube with C5v symmetry and an open edge stabilized by triple bonds.

Journal Article↗
PubMed1996

Single-epoch neuromagnetic signals during epileptiform activities in guinea pig longitudinal CA3 slices.

Neuromagnetic fields with high signal-to-noise ratios can be measured above longitudinal CA3 slices of the guinea pig during single epochs of interictal- and ictal-like synchronized population activities. Technical refinements enabled us to reduce the number of epochs for clear responses from over 5000 needed in an earlier study to single epochs. Simultaneous recording of field potentials revealed that neuromagnetic fields reflect intracellular currents in the pyramidal cells. Intracellular currents could be estimated from the external magnetic fields during paroxysmal depolarization shifts, multiple bursts, and slowly varying potential shifts lasting several seconds.

Animals↗
PubMed1996

Neuronal activities from a deep subcortical structure can be detected magnetically outside the brain in the porcine preparation.

We assessed whether subcortical structures can generate magnetic fields detectable outside the brain by first measuring the somatic evoked magnetic fields (SEFs) from a decorticated porcine preparation and then from an intact preparation. Strong SEFs were detected a few millimeters above the corpus callosum after electrical stimulations of the snout. The waveforms consisted of a large spike ( < or = 6 pT) with a peak latency of 11-18 ms depending on the age of the animal, followed by a slow wave. The waveform and latency of the SEF spike were virtually identical to those of the field potential within the brain. The SEF topography indicated that the underlying generator of the spike was in a region contralateral to the stimulation and inferior to the thalamus. The subcortical SEF was strong enough to be detectable even above the intact brain, after the cortically generated SEF was removed by ablation of the primary cortical area. The results indicate that a structure deep in the brain can produce remarkably strong magnetic fields detectable outside the brain.

Animals↗
PubMed1996

[3H]WIN 35,428 [2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane] binding to rat brain membranes. Comparing dopamine cell body areas with nerve terminal regions.

Potential differences between somatodendritic acid and axonal dopamine transporters were examined by comparing the binding constants of [3H]WIN 35, 428 [2 beta-carbomethoxy- 3 beta-(4-fluorophenyl)tropane] binding to membranes prepared from the rat ventral mesencephalon, containing A9 and A10 dopamine cell bodies, and from the nucleus accumbens. Saturation analysis of [3H]WIN 35,428 binding, in the presence of compounds to occlude norepinephrine and serotonin transporters, was performed by both the "unlabeled" method (varying unlabeled ligand) and "labeled" method (varying radioligand). The density of binding was substantially lower in the ventral mesencephalon than in the nucleus accumbens, but the binding affinity was only slightly different. Likewise, the differences between the two regions in the inhibitory potency of cocaine and GBR 12909 [1-(2-di(4-fluorophenyl)-methoxy-ethyl)4-(3-phenylpropyl)piperazine] were not substantial. The results suggest that somatodendritic and axonal dopamine transporters in the ventral mesencephalon and nucleus accumbens are not very different as far as their binding domains for uptake blockers such as cocaine and GBR 12909 are concerned.

Animals↗
PubMed1996

Structure-activity relationship studies of novel 4-[2-[bis(4-fluorophenyl)methoxy]ethyl]-1-(3-phenylpropyl)piperidine analogs: synthesis and biological evaluation at the dopamine and serotonin transporter sites.

Several analogs of the potent dopamine (DA) transporter ligand 4-[2-[bis(4-fluorophenyl)-methoxy]ethyl]-1-(3-phenylpropyl)piperidine, 1b, were made and biologically evaluated for their binding at the DA and serotonin (5HT) transporters in rat striatal membranes. Different alkyl chain lengths and substitutions were introduced in these molecules to generate an optimum activity and selectivity for the DA transporter. In general, unsubstituted and fluoro-substituted compounds were the most active and selective for the DA transporter. The compound 4-[2-(diphenylmethoxy)ethyl]-1-benzylpiperidine, 9a, showed high potency and was the most selective for the DA transporter (5HT/DA = 49) in this series of compounds. Some of these novel analogs were found to be more selective in binding at the DA transporter than the original GBR 12909 molecule, 1-[2-]bis(4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperidine.

Animals↗
PubMed1996

The chromosomal arsR gene of Escherichia coli encodes a trans-acting metalloregulatory protein.

Plasmid-encoded arsenical resistance (ars) operons confer high level resistance to arsenicals and antimonials, while the chromosomally encoded ars operon of Escherichia coli bestows low level resistance. The transcriptional start site of the chromosomal ars mRNA was mapped by primer extension, and putative -10 and -35 promoter recognition sites were identified. The arsR gene, the first gene in this operon, was cloned using polymerase chain reaction. The arsR gene product, the ArsR repressor, was expressed and purified. The results of gel mobility shift assays indicated that the repressor is a DNA binding protein that binds to a fragment of DNA containing the chromosomal ars promoter. The specific binding site, as determined by DNase I footprint analysis, spans 33 nucleotides in the promoter region, including the putative -35 promoter element. By construction and expression of a series of in-frame fusions between truncated arsR genes and the coding region for the mature form of beta-lactamase (blaM'), it was shown that ArsR is a trans-acting repressor that regulates expression of the chromosomal ars operon. In addition, the chromosomally-encoded repressor can regulate expression of the ars operon of plasmid R773, and the R773 repressor can cross-regulate expression from the chromosomal operon.

Amino Acid Sequence↗
PubMed1996

In vivo studies of cadmium-induced apoptosis in testicular tissue of the rat and its modulation by a chelating agent.

In vivo CdCl2-induced apoptotic DNA fragmentation in the testes of the male Wistar rat has been demonstrated on agarose gel. Characteristic DNA migration patterns (laddering) provide evidence of apoptosis (programmed cell death) in testicular tissue of rats administered CdCl2 at a level of 0.03 mmol/kg 48 h previously. Evidence that administration of an appropriate cadmium chelating agent within the first 24 h can suppress some or all of the apoptotic changes in testicular DNA has also been obtained for the first time. A greater reduction in apoptosis is observed as the interval between the administration of the cadmium and that of the chelating agent is shortened. Administration of monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) to male Wistar rats given CdCl2 is effective in the modulation of the typically apoptotic DNA fragmentation and associated histopathologic injury when the antagonist is given within approximately 1 h after the CdCl2 exposure. When the antagonist is given at later times there is a progressively more pronounced degradation of the DNA into oligonucleotides as seen in the typical electrophoretic DNA ladder pattern found with apoptosis. There is also a progressive increase in histopathological tissue changes as the antagonist is administered at progressively greater intervals after the cadmium.

Animals↗
PubMed1996

Effects of hyperthyroidism on expression of a phosphoenolpyruvate carboxykinase/bovine growth hormone gene in transgenic mice.

Thyroid hormone (T3) responsiveness of the PEPCK promoter in vivo was examined in both PEPCK/bGH(460) and PEPCK/bGH(335) mouse lines. Transgenic and non-transgenic littermates were treated with methimazole or PTU for 6 or 4 weeks, respectively, then treated +/- T3 for 10 days. In PEPCK/bGH(460) and PEPCK/bGH(355) transgenic mice, the bGH mRNA was decreased by 65% and 46%, respectively, in hyperthyroid mice when compared to euthyroid controls. Endogenous PEPCK mRNA was decreased by 33% in hyperthyroid non-transgenic mice. The conclusion of this study is that chronic hyperthyroidism in mice inhibits PEPCK-directed expression of the transgene when either the -460/+73 or the -355/+73 promoter/regulatory elements are used.

Animals↗
PubMed1996

In situ monitoring with the Tradescantia bioassays on the genotoxicity of gaseous emissions from a closed landfill site and an incinerator.

A dual monitoring system composed of the Tradescantia-Micronucleus (Trad-MCN) and Tradescantia-Stamen-Hair-Mutation (Trad-SHM) bioassays was utilized to monitor directly the genotoxicity of the gaseous emission at a closed landfill site and around an incinerator. Four of the commonly emitted gaseous agents from the landfill flare pipes, i.e. toluene, ethylbenzene, trichloroethylene and ethyltoluene were also evaluated for their genotoxicity in the laboratory. The in situ monitoring trips (360 km one way) were carried out by transporting the plant cuttings in a clean air box or in an air-tight plastic bag to the site and exposing these test cuttings for 5-7 h. The exposed plant samples were examined for micronuclei frequencies or the pink mutation rate after the appropriate recovery periods (24 h for MCN, 7-11 days for SHM). A total of 20 monitoring trips were made to the landfill, and 8 to the nearby surroundings (100-500 m from the chimney) of the incinerator site in a two year period. The major findings of the Trad-MCN test on the clastogenicity of the gaseous emission from the flare pipe of the landfill site showed positive responses or toxic effects in 6 out of 20 trips, and that from the incinerator showed positive responses in 5 out of the 8 trips. These positive responses were closely associated with the weather, i.e. low wind velocity, high temperature and relative humidity, and especially the distance from the chimney of the incinerator. The MCN frequencies and mutation rates of the Elementary School site (E. Sch) which is about 200 m from the fence of the landfill site were mostly negative, except the test results of three trips. Trad-SHM tests on the mutagenicity of gaseous emissions from the flare pipe of the landfill showed 12 positive responses out of 20 trials and 2 positives out of 4 trials from the incinerator gaseous emissions. The average mutation rate from 20 Trad-SHM monitoring trips is positive when the ANOVA and Dunnett's t-statistic were applied to the consolidated data. There is a significant (0.01) difference between the lab control and the gas exposed groups, and between the field control and gas exposed groups. Results of the Trad-SHM test at the E. Sch. site were mostly negative except for one trip. In general, micronuclei frequencies and mutation rates of the field control groups were relatively higher than those of the lab controls. The Trad-MCN test on pure gases showed positive responses in all 3 repeated tests on toluene (50-892 ppm). The test results of ethylbenzene yielded positive responses at 172 ppm/min and 1549 ppm/min dosages and exhibited toxicity at higher concentrations. Trad-MCN tests on trichloroethylene and ethyltoluene yielded positive responses at around 100-200 ppm/min level. Three repeated Trad-SHM tests on toluene yielded no positive response at low concentrations (4.3-12.9 ppm).

Air Pollutants↗
PubMed1996

Long-term follow-up of minimal residual disease in childhood acute lymphoblastic leukemia patients by polymerase chain reaction analysis of multiple clone-specific or malignancy-specific gene markers.

Two types of markers, namely the clone-specific markers including T-cell receptor (TCR) gamma, TCR delta, and Ig heavy-chain (IgH) gene rearrangements, and malignancy-specific fusion gene mRNA such as SIL-TAL-1, BCR-ABL, and HRX-partner genes, were investigated by molecular biology techniques in 65 Chinese patients with acute lymphoblastic leukemia (ALL). In combination, these markers were informative among 96% of patients. Minimal residual disease (MRD) was followed up in 23 of these patients with available materials over a period varying from 8 to 54 months with at least one leukemia-specific probe. In most children, MRD was decreased continuously to an ultimately undetectable level within 6 to 12 months after remission induction therapy. One patient exhibited low-level residual leukemic cells for 4 years before the MRD turned negative. Another patient remained in complete remission for 45 months, although a positive signal was detected at 34 months using TCR delta probe, but was negative with a TCR gamma marker which was positive at presentation. In three patients who relapsed, MRD either persisted through the clinical course or became positive and eventually increased 3-11 months before clinical relapse. These data suggested that the combined use of multiple gene markers is a valuable tool for the PCR-based MRD detection, since it can cover most ALL patients. Furthermore, long-term follow-up of MRD is helpful for determining the dosage as well as the period of maintenance chemotherapy and for predicting impending relapse.

Base Sequence↗
PubMed1996

Cadmium mobilization by nitrogen donor chelating agents.

The relative abilities of a series of acyclic polyamine chelating agents containing only nitrogen donors (N-donors) to induce the urinary excretion of cadmium has been examined in the rat. The compounds examined include triethylenetetramine dihydrochloride (TRIEN), tris(2-aminoethyl)amine trihydrochloride (TREN), tetraethylenepentamine pentahydrochloride (TETRAEN), and pentaethylenehexamine hexahydrochloride (PENTAEN). Sodium N-methyl-D-glucamine-N-carbodithioate (NaG) was used as a positive control compound. The polyamines induced a significant increase in the urinary excretion of cadmium in rats that had been loaded with cadmium at least 4 d prior to the polyamine treatments. A comparison of these with similar data on macrocylic nitrogen donor systems, which form much more stable complexes with cadmium but are also ineffective in enhancing the excretion of cadmium from such aged deposits, suggests that the factors responsible for the relative inefficiency of these compounds may involve either a difficulty in penetrating cellular membranes or a slow rate of reaction with biologically bound cadmium. The occurrence of oliguria and anuria following the administration of the several of the polyamines indicates that their use is accompanied by significant renal damage in cadmium-exposed rats.

Animals↗
PubMed1996

Fluoroquinolone resistance associated with specific gyrase mutations in clinical isolates of multidrug-resistant Mycobacterium tuberculosis.

Fluoroquinolones are potent antibacterial agents being used clinically against multidrug-resistant tuberculosis. Treatment failure is thought to arise from acquisition of fluoroquinolone resistance by Mycobacterium tuberculosis. A collection of 13 resistant clinical isolates of M. tuberculosis was examined for ciprofloxacin sensitivity relative to controls exhibiting the same IS6110 DNA type. Specific alleles were associated with distinct levels of drug susceptibility for 11 isolates that contained nucleotide changes expected to alter the amino acid sequence of the A subunit of DNA gyrase. Five different gyrA (ciprofloxacin resistance) alleles were present among 7 isolates having the W DNA subtype. These isolates, which are representative of an outbreak strain, constitute a panel of organisms that can be used to evaluate contributions of gyrase and DNA topoisomerase IV to resistance.

Anti-Infective Agents↗