Biomedical subjects

J Shen

Publications and source records attributed to J Shen.

At least 37 records · Page 2Linked to original sources

PubMed2006

[Development of a rapid subtype-screening assay for the env region of HIV-1 CRF strains in Guangxi.].

BACKGROUND: To develop a simple and rapid subtype-screening assay for the env region of the circulating recombinant form (CRF) of human immunodeficiency virus type 1 (HIV-1) in Guangxi. METHODS: Proviral DNA from HIV-1 positive samples were extracted and subjected to the first round PCR with universal primers for the env region that can detect HIV-1 M group isolates. In the second round PCR, two pairs of subtype-specific primers that were designed to detect subtype C or B'/C and CRF01-AE respectively were added into one tube. The PCR products of different subtypes could be distinguished in agarose-gel electrophoresis. Additionally, all of these samples were sequenced and analyzed phylogenetically. RESULTS: Phylogenetic analysis of the env region of 50 samples showed that 3 samples (6%) were infected with CRF08-BC, 43 (86%) with CRF01-AE, and 4 (8%) remained unclassifiable. Detection of the subtype-specific primer sets revealed that 3 were subtype C or B'/C (100%), 39 were CRF01-AE (90.7%), with an adequate sensitivity (91.3%) and a high specificity (100%). Non-specific bands occasionally appeared but did not interfere with interpretation of the results. The phylogenetic analysis was consistent with subtype-specific primer sets and the consistency rate was 92%. The average reproducibility was 100% for CRF08-BC samples and 93.8% for CRF01-AE samples. CONCLUSION: A simple, rapid and low cost assay was developed for subtype-screening of CRF01-AE in Guangxi.

China↗

PubMed2005

"Live" surface ferromagnetism in Fe nanodots/Cu multilayers on Cu(111).

We investigate the crossover behavior from two-dimensional (2D) to three-dimensional in multilayers of magnetic nanodots grown by stacking 2D Fe nanodot assemblies on Cu(111) single crystal substrate with a Cu spacing layer. Using an in situ magneto-optical Kerr effect, we have observed a striking ferromagnetic to spin-glass-like phase transition with an increasing number of Fe dot layers. The topmost layer of the Fe dots survives the phase transition and remains ferromagnetic. This unusual surface ferromagnetism is likely caused by a surface-state-mediated coupling which is stronger than the coupling in bulk layers. This is confirmed by the fact that the critical temperature of the surface ferromagnetism is considerably higher than that of the bulk spin-glass phase in the system.

Journal Article↗

PubMed2005

Visualization of localized holes in manganite thin films with atomic resolution.

The magnetic and transport behaviors of manganites are critically related to the spatial distribution and correlation of doped holes. Using in situ scanning tunneling microscopy, we have imaged both occupied and unoccupied states simultaneously in a hole-doped (La(5/8-0.3)Pr0.3)Ca(3/8)MnO3 epitaxial thin film grown by laser molecular beam epitaxy. Doped holes localized on Mn4+ ion sites were directly observed with atomic resolution in the paramagnetic state at room temperature. In contrast to a random distribution, these doped holes show strong short-range correlation and clear preference of forming nanoscale CE-type charge-order-like clusters. The results provide direct visualization of the nature of intriguing electronic inhomogeneity in transition metal oxides.

Journal Article↗

PubMed2005

Analysis of T-cell responses in malaria-exposed and non-exposed donors using Plasmodium falciparum asexual blood stages enriched by a simple centrifugation method.

Several studies have reported on similar in vitro cellular responses to different malaria-antigen preparations in both malaria-primed and un-primed donors. Whether intact live parasites can exert a distinct type of response in either of the two groups is not well known. In this study, we developed a simple three-step centrifugation method for simultaneous enrichment of early and late blood stages from Plasmodium falciparum cultures. Such enriched P. falciparum fractions and other antigen preparations were used to stimulate lymphocytes from malaria-exposed and non-exposed individuals to examine the proliferative activity and expansion of CD3+, gammadelta+, CD4+, and CD8+ T cells. While lymphocytes from malaria non-exposed donors proliferated relatively higher than those from malaria-exposed donors in response to most antigens tested, the enriched fractions of live parasites exerted higher proliferative responses on cells from the latter donors. This suggests the existence of memory cells in the malaria-exposed donors, but not in the non-exposed ones. Flow cytometric analysis revealed a higher percentage expansion of CD4+ T cells in the responding cells of the exposed donors than the non-exposed ones. Taken together, this study reports on a simple method that simultaneously enriches for intact live early and late blood stages of P. falciparum parasites. Moreover, the study revealed higher expansion CD4+ T cells in the exposed individuals than the non-exposed in response to live malaria parasites and not to other parasite-antigen preparations.

Animals↗

PubMed2005

In vivo evidence for reduced cortical glutamate-glutamine cycling in rats treated with the antidepressant/antipanic drug phenelzine.

Converging evidence has indicated that hyperglutamatergic activity and GABAergic dysfunction may play important roles in the neurobiology and treatment of depression and other mood disorders. In this study, in vivo 1H[13C] magnetic resonance spectroscopy was used to quantify the effects of acute phenelzine administration on cortical energetics, glutamate neurotransmission, and GABA synthesis flux. The time-resolved kinetics of cortical [4-13C]glutamate, [4-13C]glutamine, and [2-13C]GABA turnover from i.v.-infused [1,6-13C2]glucose was measured at 11.7 T in alpha-chloralose anesthetized rats four hours after phenelzine treatment (10 mg/kg, i.p.) and in non-treated controls. The rate of the tricarboxylic acid cycle flux was not affected by phenelzine treatment compared with the non-treated group (0.46+/-0.05 vs. 0.50+/-0.05 micromol/g/min, respectively). The rate of the glutamate-glutamine cycling flux between neurons and glia in the phenelzine-treated group was significantly reduced (from 0.16+/-0.04 to 0.10+/-0.03 micromol/g/min), providing in vivo evidence that phenelzine attenuates glutamate neurotransmission. Following phenelzine treatment, the cortical GABA concentration increased significantly (from 1.02+/-0.17 to 2.30+/-0.26 micromol/g), while the GABA synthesis flux was unchanged (from 0.07+/-0.02 to 0.06+/-0.02 micromol/g/min). The possible role of augmented GABAergic function resulting from elevated GABA levels in the observed modulatory effect of phenelzine on the glutamate-glutamine cycling flux was discussed. The reduced glutamate-glutamine cycling flux observed in this study suggests that, in addition to its effects on monoaminergic and GABAergic systems, the attenuation of glutamate neurotransmission resulting from phenelzine administration may also contribute to its efficacy in the treatment of depression. This study is the first demonstration that the glutamate-glutamine cycling flux, which can be measured non-invasively in the human brain in vivo, was altered due to the action of a psychotropic drug.

Animals↗

PubMed2005

Failure to find association between TRAR4 and schizophrenia in the Chinese Han population.

The TRAR4 gene locates in SCZD5 (MIM 603175), which a number of studies have linked with schizophrenia. One recent study suggested that three TRAR4 variants (M1: rs4305745, P=0.0014; M2: rs6903874, P=0.0026; M3: rs6937506, P=0.0052) in the 3'-UTR were associated with schizophrenia. To replicate these findings, we conducted a family-based association study within a sample of 235 Chinese Han trios. However, we didn't find significant evidence of preferential transmission of the three variants across all the trios (all P values>0.2). Thus, we conclude that TRAR4 is not a major or independent determinant in the occurrence of schizophrenia in the Chinese Han population.

Adult↗

PubMed2005

Integrated RF probe for in vivo multinuclear spectroscopy and functional imaging of rat brain using an 11.7 Tesla 89 mm bore vertical microimager.

To acquire high quality in vivo NMR data from rat brain using a vertical 89-mm bore magnet, specially designed NMR probes with integrated RF coils and animal handling capability are required. An RF probe design that is also capable of rat head fixation, body support and suitable for physiology monitoring and maintenance was constructed for an 89 mm bore, 11.7 T, vertical microimager which is equipped with a 57-mm i.d. gradient insert. Design concept and practical aspects of probe construction are described in detail. The device allows accurate and highly reproducible positioning of rat head inside the magnet while providing excellent RF performance. Typical results from fMRI, localized in vivo proton and multinuclear spectroscopy using this probe system are presented.

Animals↗

PubMed2005

Frozen low-spin interface in ultrathin Fe films on Cu(111).

In ultrathin film systems, it is a major challenge to understand how a thickness-driven phase transition proceeds along the cross-sectional direction of the films. We use ultrathin Fe films on Cu(111) as a prototype system to demonstrate how to obtain such information using an in situ scanning tunneling microscope and the surface magneto-optical Kerr effect. The magnetization depth profile of a thickness-driven low-spin to high-spin magnetic phase transition is deduced from the experimental data, which leads us to conclude that a low-spin Fe layer at the Fe/Cu interface stays live upon the phase transition. The magnetically live low-spin phase is believed to be induced by a frozen fcc Fe layer that survives a thickness-driven fcc-->bcc structural transition.

Journal Article↗

PubMed2005

Modeling of configurations and third-order nonlinear optical properties of methyl silsesquioxanes.

Configuration optimizations, excited state properties, and the frequency-dependent third-order nonlinear optical polarizabilities have been investigated on a series of methyl-silsesquioxane (MeT) cages [CH(3)SiO(1.5)](n) (n=4, 6, 8, and 10) using ab initio quantum mechanical methods coupled with the sum-over-states methods. The obtained electronic absorption spectra show a redshift as the cage size increases, and the absorption spectra are assigned as charge transfers from oxygen p type to silicon s type atomic orbitals. The calculated average third-order polarizabilities of in the three optical physical processes (third-harmonic generation, the electric-field-induced second-harmonic generation, and degenerate four-wave mixing) have wide nonresonance regions. For all the considered species, the values of gamma decrease in the order of [MeT](4)>[MeT](8)(C(2v))=[MeT](10)>[MeT](6)>[MeT](8)(O(h)).

Journal Article↗

PubMed2005

Theoretical study on the photophysical properties of hexapyrrolidine C60 adducts with Th, D3, and S6 symmetries.

The equilibrium geometries of three isomeric hexapyrrolidine C(60) adducts with T(h), D(3), and S(6) symmetries are optimized by means of the B3LYP method at the 6-31G basis sets in this paper. On the basis of the optimized structures, the excited state and third-order nonlinear optical properties, such as third-harmonic generation (THG), electric-field-induced second-harmonic generation (EFISHG), and degenerate four-wave mixing (DFWM), and two-photon absorption (TPA) cross sections, delta, are calculated by using the TDB3LYP model based on the 6-31G level coupled with the sum-over-states (SOS) method. The computational results show that the transition energies from S(0) to S(1) of the T(h) hexaadduct and the D(3) hexaadduct have a remarkable blue shift by comparison with that of the C(60) parent. These results are in agreement with experimental ones. However, the first singlet excitation energy of the S(6) hexaadduct has a red shift compared with that of the C(60) parent. Accordingly, we predict that different positions located by six addends may result in the different spectrum properties. Finally, the two-photon absorption cross sections indicate that the largest average value of resonant TPA, delta, of the D(3) hexaadduct has a red shift compared with those of the T(h) and S(6) hexaadducts.

Journal Article↗

PubMed2005

Acute effects of glucocorticoids on ATP-induced Ca2+ mobilization and nitric oxide production in cochlear spiral ganglion neurons.

Rapid, non-genomic effects of glucocorticoids on extracellular adenosine 5'-triphosphate (ATP)-induced intracellular Ca(2+) concentration ([Ca(2+)](i)) changes and nitric oxide (NO) production were investigated in type I spiral ganglion neurons (SGNs) of the guinea-pig cochlea using the Ca(2+)-sensitive dye fura-2 and the NO-sensitive dye 4,5-diaminofluorescein (DAF-2). Pretreatment of SGNs with 1 microM dexamethasone for 10 min, a synthetic glucocorticoid hormone, enhanced the ATP-induced [Ca(2+)](i) increase in SGNs. RU 38486, a competitive glucocorticoid receptor antagonist eliminated the effects of dexamethasone on the ATP-induced [Ca(2+)](i) increase in SGNs. These acute effects of dexamethasone were dependent on the presence of extracellular Ca(2+), thereby suggesting that dexamethasone may rapidly enhance the Ca(2+) influx through the activation of ionotropic P2X receptors which may interact with glucocorticoid-mediated membrane receptors. Extracellular ATP increased the intensity of DAF-2 fluorescence, indicating NO production in SGNs. The ATP-induced NO production was mainly due to the Ca(2+) influx through the activation of P2 receptors. S-nitroso-N-acetylpenicillamine, a NO donor, enhanced the ATP-induced [Ca(2+)](i) increase in SGNs while L-N(G)-nitroarginine methyl ester (L-NAME), a NO synthesis inhibitor, inhibited it. Dexamethasone enhanced the ATP-induced NO production in SGNs. The augmentation of dexamethasone on ATP-induced NO production was abolished in the presence of l-NAME. It is concluded that the ATP-induced [Ca(2+)](i) increase induces NO production which enhances a [Ca(2+)](i) increase in SGNs by a positive-feedback mechanism. Dexamethasone enhances the ATP-induced [Ca(2+)](i) increase in SGNs which results in the augmentation of NO production. The present study suggests that NO may play an important role in auditory signal transduction. Our results also indicate that glucocorticoids may rapidly affect auditory neurotransmission due to a novel non-genomic mechanism.

Adenosine Triphosphate↗

PubMed2005

Development and characterization of human constitutive proteasome and immunoproteasome subunit-specific monoclonal antibodies.

Delta (Y), MB1 (X), and Z are the three catalytic beta-subunits located in the inner rings of the constitutive proteasome, an intracellular multicatalytic complex responsible for the generation of peptides presented by human leukocyte antigen (HLA) class I antigens to T cells. When cells are incubated with interferon-gamma, delta (Y), MB1 (X), and Z are replaced by LMP2, LMP7, and LMP10, respectively, leading to the expression of immunoproteasome which generates peptides with increased affinity for HLA class I antigens. The characterization of the expression of constitutive proteasome and immunoproteasome subunits in cells, normal tissues, and malignant lesions has been hampered by the lack or limited availability of constitutive proteasome and immunoproteasome subunit-specific monoclonal antibodies (mAbs), which are suitable for immunohistochemical staining. To overcome this limitation, we generated human delta (Y), MB1 (X), Z, LMP2, LMP7, and LMP10-specific mAb-secreting hybridomas from BALB/c mice immunized with peptides and recombinant fusion proteins. The mAbs SY-5, SJJ-3, NB-1, SY-1, HB-2, and TO-7 were shown to be specific for delta (Y), MB1 (X), Z, LMP2, LMP7, and LMP10, respectively, as they react specifically with the corresponding molecules when tested with a human B lymphoid LG2 cell lysate in Western blotting and with the peptide derived from each molecule in enzyme-linked immunosorbent assay. The reactivity of the six mAbs with the corresponding intracellular antigens resulted in intracellular staining when the mAbs were tested with microwave-treated and saponin-permeabilized cells in indirect immunofluorescence and with formalin-fixed, paraffin-embedded tissue sections in immunohistochemical reactions. These results suggest that the constitutive proteasome and immunoproteasome subunit-specific mAbs we have developed are useful probes to characterize the expression of proteasome subunits in normal tissues and in pathological lesions.

Animals↗

PubMed2005

Molecular correlates of emotional learning using genetically selected rat lines.

The genetic contributions to active avoidance learning in rodents have been well established, yet the molecular basis for genetically selected line differences remains poorly understood. To identify candidate genes influencing this active avoidance paradigm, we utilized the bidirectionally selected Syracuse high- and low-avoidance (SHA and SLA) rat lines that markedly differ in their two-way active avoidance behavior. Rats were phenotyped, rested to allow recovery from testing stress and then hippocampi were dissected for gene expression profiling (Affymetrix U34A chips; approximately 7000 known genes), comparing SLA to SHA. Next, a subset of differentially expressed genes was confirmed by real-time PCR (RT-PCR) in hippocampi. Additional studies at the protein level were performed for some genes. Using triplicate arrays on pooled hippocampal samples, differentially expressed genes were identified by microarray suite 5.0 and robust multi-array average analyses. By RT-PCR analysis in hippocampi, eight genes were nominated as potential candidate genes consistent with the differential expression from the microarray data. Four genes, Veli1 (mlin-7B), SLC3a1, Ptpro and Ykt6p, showed higher expression in SHA hippocampi than SLA. Four genes, SLC6A4, Aldh1a4, Id3a and Cd74, showed higher expression in SLA hippocampi than SHA. The active avoidance behavioral difference between lines probably emerges from 'many small things'. These potential candidate genes generate hypotheses for future testing in human association and rodent studies. Differences in levels of a pleiotropic gene like Ptpro and SLC6A4 suggest that small differences over a lifespan may contribute to large behavioral differences.

Animals↗

PubMed2005

ASPM mutations identified in patients with primary microcephaly and seizures.

BACKGROUND: Human autosomal recessive primary microcephaly (MCPH) is a heterogeneous disorder with at least six genetic loci (MCPH1-6), with MCPH5, caused by ASPM mutation, being the most common. Despite the high prevalence of epilepsy in microcephaly patients, microcephaly with frequent seizures has been excluded from the ascertainment of MCPH. Here, we report a pedigree with multiple affected individuals with microcephaly and seizures. OBJECTIVE: To identify the gene responsible for microcephaly and seizures in this pedigree. METHODS: Clinical assessments of three patients and brain MRIs of two patients were obtained. Genome-wide linkage screen with 10 k SNP microarray, fine mapping with microsatellite markers, and mutational analysis of the genomic DNA were performed on the pedigree. RESULTS: We found that the family was linked to the MCPH5 locus on chromosome 1q31.2-q32.1. We screened ASPM and identified a previously unreported nonsense mutation that introduced a premature stop codon in exon 18 of the ASPM gene. CONCLUSIONS: We thus expand the clinical spectrum of ASPM mutations by showing that they can occur in patients with seizures and that the history of seizures alone should not necessarily preclude the diagnosis of primary microcephaly.

Brain↗

PubMed2005

HPLC determination of telmisartan in human plasma and its application to a pharmacokinetic study.

A sensitive, simple, and accurate HPLC method was developed for the assay of telmisartan in human plasma. Using naproxen as internal standard, the assay involved liquid-liquid extraction of the compound from acidified plasma into organic solvent and reversed-phase chromatography with fluorescence detection. The assay was shown to be linear from 0.5 to 1000 ng/mL. In 24 healthy volunteers, the plasma concentrations of the drug were determined after a single oral dose of 160 mg.

Adult↗

PubMed2004

Surface modification using photocrosslinkable chitosan for improving hemocompatibility.

Immobilization of the anticoagulative or antithrombogenic biomolecule has been considered as one of the important methods to improve the blood compatibility of artificial biomaterials. In this study, a novel immobilization reaction scheme was utilized to incorporate O-butyrylchitosan (OBCS) onto the activated glass surface with an aim to develop an anticoagulative substrate. Activation of the glass surface was carried out by silanization and then OBCS was grafted to the silanized surface via a radiation grafting technique. The OBCS-grafted glass surfaces were characterized by electron spectroscopy for chemical analysis (ESCA) and atomic force microscopy (AFM). The blood compatibility of the OBCS-grafted glass was evaluated by platelet rich plasma (PRP) contacting experiments and protein adsorption experiments in vitro. These results have demonstrated that the surface with immobilized OBCS shows much less platelet adhesive and fibrinogen adsorption compared to the control surface. Therefore, the novel reaction scheme proposed here is very promising for future development of an anticoagulative glass substrate.

Blood Coagulation↗

PubMed2004

Modeling of configurations and third-order nonlinear optical properties of C(36) and C(34)X(2) (X=B,N).

Using the ab initio method, the geometrical structures of C(36) and the X (B,N)-doped isomers C(34)X(2) have been optimized. On the basis of the optimized structures, then, the third-order nonlinear optical polarizabilities gamma in the different optical processes of the third-harmonic generation, electric-field induced second-harmonic generation and degenerate four-wave mixing, and two-photon absorption (TPA) cross sections delta are calculated by using TDB3LYP method coupled with the sum-over-states method. The calculated results show that the one-photon allowed excitation process dominate the two-photon excitation process for C(36)-D(6h), whereas the two-photon allowed excitation process dominate the one-photon excitation process for C(36)-D(2d) and C(34)X(2) (B,N). It is found that the largest resonant TPA peaks of dopant fullerenes have a blueshift and the TPA cross sections have an enhancement compared with those of the parent fullerenes of isomers C(36)-D(6h) and C(36)-D(2d).

Journal Article↗

PubMed2004

Outcomes of newly referred neurology outpatients with depression and pain.

BACKGROUND: Although depression and pain are common in neurology outpatients, patient factors influencing chronicity are poorly understood. The authors sought to determine the predictors of persistent depression and pain symptoms at 3 and 12 months after an initial outpatient neurology clinic visit. METHODS: Consecutive new patients (n = 483) at three clinics completed the Patient Health Questionnaire nine-item depression scale and the Brief Pain Inventory at baseline and at 3- and 12-month follow-up. Multivariate analysis was used to model 3- and 12-month depression and pain severity. RESULTS: The prevalence of depression and pain at baseline/3/12 months was depression 33%/28%/27% and pain 66%/61%/62%. Independent predictors of depression severity at follow-up were more severe depression and pain at baseline and less improvement in pain (model r(2) = 0.53 to 0.56). Independent predictors of pain intensity at follow-up were more severe pain and depression at baseline and less improvement in depression (model r(2) = 0.44 to 0.46). Health care utilization and impairments in health status were greatest in patients with coexisting depression and pain and least in those with neither depression nor pain. CONCLUSIONS: Depression and pain symptoms in neurology outpatients often persist for at least 12 months and have long-term negative effects on patients' health status. Pain is more likely to persist in patients with depression, and depression is more likely to persist in those with coexistent pain.

Adult↗