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Biomedical subjects

T Xie

Publications and source records attributed to T Xie.

At least 19 recordsLinked to original sources

Experimental and theoretical study of the infrared spectra of BrHI- and BrDI-.

Gas phase vibrational spectra of BrHI- and BrDI- have been measured from 6 to 17 microm (590-1666 cm(-1)) using tunable infrared radiation from the free electron laser for infrared experiments in order to characterize the strong hydrogen bond in these species. BrHI-.Ar and BrDI-.Ar complexes were produced and mass selected, and the depletion of their signal due to vibrational predissociation was monitored as a function of photon energy. Additionally, BrHI- and BrDI- were dissociated into HBr (DBr) and I- via resonant infrared multiphoton dissociation. The spectra show numerous transitions, which had not been observed by previous matrix studies. New ab initio calculations of the potential-energy surface and the dipole moment are presented and are used in variational ro-vibrational calculations to assign the spectral features. These calculations highlight the importance of basis set in the simulation of heavy atoms such as iodine. Further, they demonstrate extensive mode mixing between the bend and the H-atom stretch modes in BrHI- and BrDI- due to Fermi resonances. These interactions result in major deviations from simple harmonic estimates of the vibrational energies. As a result of this new analysis, previous matrix-isolation spectra assignments are reevaluated.

Journal Article↗

Human catechol-O-methyltransferase down-regulation by estradiol.

Catechol-O-methyltransferase (COMT) is a crucial enzyme in dopamine and levodopa metabolism. Previously we reported that physiological concentrations of 17beta-estradiol (E2) down-regulated steady-state 1.3-kb COMT mRNA levels in MCF-7 cells. In this study, we investigated whether similar reductions occurred in a glial cell line (U138MG) and whether COMT protein and activity levels paralleled the reduction in COMT mRNA levels in MCF-7 cells. In addition, we explored the mechanism of E2 action. E2 had no effect on COMT mRNA levels in U138MG cells, but significantly reduced COMT protein and activity in MCF-7 cells (activity by 53% at 10(-7) M of E2, by 45% at 10(-8) M, and by 28% at 10(-9) M relative to non-E2-treated cells). A specific estrogen receptor antagonist (ICI 182780) blocked these estrogenic effects. Estrogen receptor in nuclear extracts of MCF-7 cells, which were pretreated with E2 (10(-9) M) for 48 h, bound to the whole proximal and distal promoter regions, as determined by electrophoretic mobility shift analysis (EMSA). We propose that E2 decreased COMT activity through down-regulation of its gene and protein expression mediated via ER interaction with response elements in the promoter region of the gene. Our findings may explain the lower of COMT activity in women compared to that in men, and, in part, the beneficial effects of E2 therapy in post-menopausal Parkinson's disease patients.

Antibody Specificity↗

The structure dependent electrochemical-response of novel 1-(4-mercaptobutyl)-4-(2-ferrocenylvinyl)pyridinium bromide SAMs on an au electrode.

The 1-(4-mercaptobutyl)-4-(2-ferrocenylvinyl)pyridinium bromide (1-HS(CH2)(4)-4-[(E)-FcCH=CH]C5H4N)+Br- and its hydrogenated product [1-HS(CH2)(4)-4-(-FcCH2CH2)C5H4N]+Br- were synthesized and assembled on an Au electrode to form self-assembled monolayers which showed a structure-dependent electrochemical-response in phosphate buffer aqueous solutions (pH = 7).

Journal Article↗

A murine dopamine neuron-specific cDNA library and microarray: increased COX1 expression during methamphetamine neurotoxicity.

Due to brain tissue heterogeneity, the molecular genetic profile of any neurotransmitter-specific neuronal subtype is unknown. The purpose of this study was to purify a population of dopamine neurons, construct a cDNA library, and generate an initial gene expression profile and a microarray representative of dopamine neuron transcripts. Ventral mesencephalic dopamine neurons were purified by fluorescent-activated cell sorting from embryonic day 13.5 transgenic mice harboring a 4.5-kb rat tyrosine hydroxylase promoter-lacZ fusion. Nine-hundred sixty dopamine neuron cDNA clones were sequenced and arrayed for use in studies of gene expression changes during methamphetamine neurotoxicity. A neurotoxic dose of methamphetamine produced a greater than twofold up-regulation of the mitochondrial cytochrome c oxidase polypeptide I transcript from adult mouse substantia nigra at 12 h posttreatment. This is the first work to describe a gene expression profile for a neuronal subtype and to identify gene expression changes during methamphetamine neurotoxicity.

3,4-Dihydroxyphenylacetic Acid↗

Real-time three-dimensional dobutamine stress echocardiography in assessment stress echocardiography in assessment of ischemia: comparison with two-dimensional dobutamine stress echocardiography.

OBJECTIVES: This study was designed to test the feasibility and efficacy of using real-time three-dimensional echocardiography (RT-3D) to detect ischemia during dobutamine-induced stress (DSE) and compares the results with conventional two-dimensional echocardiography (2D). BACKGROUND: Real-time three-dimensional echocardiography, a novel imaging technique, offers rapid acquisition with multiple simultaneous views of the left ventricle (LV). These features make it attractive for application during stress. METHODS: Of 279 consecutive patients screened for image quality by 2D, 253 patients with adequate images underwent RT-3D and 2D within 30 s of each other at baseline and at peak DSE. RESULTS: Real-time three-dimensional echocardiography and 2D showed good concordance in detection of abnormal LV wall motion at baseline (84%: Kappa = 0.59) and at peak DSE (88.9%: Kappa = 0.72). Left ventricular wall motion scores were similar at baseline and peak DSE using both techniques. Interobserver agreements for detection of ischemia at peak DSE were superior for RT-3D, 92.7% compared with 84.6% for 2D (p < 0.05). Mean scanning time at peak stress by RT-3D in 50 randomly selected patients was shorter, 27.4 +/- 10.7 s compared with 62.4 +/- 20.1 s by 2D (p < 0.0001). In 90 patients with coronary angiograms, RT-3D had a sensitivity of 87.9% in the detection of coronary artery disease (CAD) compared with 79.3% by 2D. CONCLUSIONS: Real-time three-dimensional dobutamine stress echocardiography is feasible and sensitive in the detection of CAD. The procedure offers shorter scanning time, superior interobserver agreements and unique new views of the LV.

Coronary Disease↗

Approaches to soil remediation by complexometric extraction of metal contaminants with regeneration of reagents.

Complexometric equilibrations were performed with six chelating reagents to mobilise Cu, Mn, Pb and Zn from a contaminated urban soil. The metal-laden aqueous extract was treated with sodium diethyldithiocarbamate (DEDTC) to precipitate the heavy metals from solution while liberating the chelating reagent. The aqueous supernatant fraction was then re-combined with the soil particulates to extract more pollutants. A sparing quantity of EDTA (ethylenediaminetetraacetic acid; 10 mmol) mobilised 32-54% of the 5 mmol of heavy metals from the soil with three cycles but only 0.1 and 1.0% of the iron and magnesium, respectively, was removed. Whereas DPTA (1,3-diamino-2-hydroxypropane-N,N,N',N'-tetraacetic acid) and citric acid also mobilised each of the heavy metals to some extent and continued to extract these metals during all three cycles, the DTPA (diethylenetriamine pentaacetic acid), although efficient initially, could not be recycled with these conditions. ADA [N-(2-acetamido)iminodiacetate] and SCMC [(S)-carboxymethyl-L-cysteine] were selective for copper and zinc but mobilised only Cu when recycled. An alternate means of regenerating the chelating reagent involved treatment of the aqueous extract with magnesium (Mg0) granules. Excess HEDC [bis(2-hydroxyethyl)dithiocarbamate] mobilised appreciable quantities (19-57%) of heavy metals from the soil and retained its complexing activity when recycled. An appreciable fraction of the mobilised Pb and Cu and a portion of the Zn were cemented to the surfaces of the excess magnesium whereas virtually all of the Fe and Mn was removed from solution as insoluble hydroxides.

Chelating Agents↗

Prostate cancer, benign prostatic hyperplasia and physical activity in Shanghai, China.

BACKGROUND: Studies suggest that increased levels of physical activity might decrease the risk of prostate cancer. We ascertained lifetime measures of activity in a population-based case-control study of prostate cancer in Shanghai, China to investigate physical activity in a population where the incidence of prostate cancer is low but rising. METHODS: In all, 238 men with prostate cancer, diagnosed 1993-1995, were identified through a rapid reporting system. A second group of 206 men with benign prostatic hyperplasia (BPH) was matched to prostate cancer cases, and 471 age-matched and population-based controls were identified from urban Shanghai. Through personal interviews, we ascertained all daily, occupational, and recreational activities at ages 20-29, ages 40-49, and in 1988 to generate hours spent sleeping, sitting, in moderate activity, and in vigorous activity. Time spent per week in different activities was converted to metabolic equivalents (MET-h) and energy expended. RESULTS: Time spent in, MET-h of, and energy expended in physical activities were not consistently related to either prostate cancer or BPH when compared to controls. Few men reported regular vigorous activity. Occupational activity, based on an energy expenditure index using job titles, was suggestively associated with a decreased risk of BPH, but not associated with prostate cancer. Associations did not vary according to age or stage of prostate cancer at diagnosis. CONCLUSIONS: Our results, based on regular physical activity, occupational activity, hours in activities, MET-h, and energy expended, did not support a protective role of physical activity in prostate cancer or BPH for men in a low-risk population.

Adult↗

Spinal movement and performance of a standing reach task in participants with and without Parkinson disease.

BACKGROUND AND PURPOSE: Evidence suggests that individuals with early and mid-stage Parkinson disease (PD) have diminished range of motion (ROM). Spinal ROM influences the ability to function. In this investigation, the authors examined available spinal ROM, segmental excursions (the ROM used) during reaching, and their relationships in community-dwelling adults with and without PD. SUBJECTS: The subjects were 16 volunteers with PD (modified Hoehn and Yahr stages 1.5-3) and 32 participants without PD who were matched for age, body mass index, and sex. METHODS: Range of motion of the extremities was measured using a goniometer, and ROM of the spine was measured using the functional axial rotation (FAR) test, a measure of unrestricted cervico-thoracic-lumbar rotation in the seated position. Motion during reaching was determined using 3-dimensional motion analysis. Group differences were determined using multivariable analysis of variance followed by analysis of variance. Contributions to total reaching distance of segmental excursions (eg, thoracic rotation, thoracic lateral flexion) were determined using forward stepwise regression. RESULTS: Subjects with PD as compared with subjects without PD had less ROM (FAR of 98.2 degrees versus 110.3 degrees, shoulder flexion of 151.9 degrees versus 160.1 degrees) and less forward reaching (29.5 cm versus 34.0 cm). Lateral trunk flexion and total rotation relative to the ground contributed to reaching, with the regression model explaining 36% of the variance. DISCUSSION AND CONCLUSION: These results contribute to the growing body of evidence demonstrating that spinal ROM is impaired early in PD.

Adult↗

STAT5b is required for GH-induced liver IGF-I gene expression.

Although the increased expression of Igf-I in liver in response to GH is well characterized, the intracellular signaling pathways that mediate this effect have not been identified. Intracellular signaling molecules belonging to the Janus kinase-signal transducer and activator of transcription 5b (JAK2-STAT5b) pathway are activated by GH and have previously been shown to be required for sexually dimorphic body growth and the expression of liver cytochrome P450 proteins known to be regulated by the gender-specific temporal patterns of pituitary GH secretion. Here, we evaluate the role of STAT5b in GH activation of Igf-I by monitoring the induction of Igf-I mRNA in livers of wild-type and Stat5b(-/-)mice stimulated with exogenous pulses of GH. GH induced the expression of liver Igf-I mRNA in hypophysectomized male wild-type, but not in hypophysectomized male Stat5b(-/-) mice, although the Stat5b(-/-) mice exhibit both normal liver GH receptor expression and strong GH induction of Cytokine-inducible SH2 protein (Cis), which is believed to contribute to the down-regulation of GH-induced liver STAT5b signaling. Thus, STAT5b plays an important and specific role in liver Igf-I gene expression.

Animals↗

Efficacy of treatment with antisense oligonucleotides complementary to immunoglobulin sequences of bcl-2/immunoglobulin fusion transcript in a t(14;18) human lymphoma-scid mouse model.

In t(14;18)-positive lymphoma cells, bcl-2 is expressed from a fusion mRNA transcript containing the full coding sequence of bcl-2 and 3' immunoglobulin sequences. We reported previously that antisense oligodeoxyribonucleotides directed at the bcl-2 translational start site, as well as those targeted to immunoglobulin sequences 3' of the translocation breakpoint, down-regulate bcl-2 and inhibit growth of the t(14;18)-positive lymphoma line WSU-FSCCL in vitro. We have developed a scid mouse model with this human cell line and demonstrate that antisense oligodeoxyribonucleotides targeted to immunoglobulin c(mu) sequences down-regulate bcl-2 protein expression and induce apoptosis of WSU-FSCCL cells in vivo. This leads to prolonged survival of the mice. Targeting non-oncogenic sequences outside of the breakpoints of fusion transcripts may be a clinically useful therapeutic strategy.

Animals↗

Investigating 42 candidate orthologous protein groups by molecular evolutionary analysis on genome scale.

It is one of key problems for comparative genomics to accurately identify orthologous genes/proteins. Here 42 quartettes of human, yeast Saccharomyces cerevisiae, nematode Caenorhabditis elegans, and fruit fly Drosophila melanogaster candidate orthologs, defined by using similarity-based highest hit criteria (Mushegian et al., 1998 Genome Res. 8: 590-598), were reconsidered according to molecular evolutionary analysis. We found that only 14 of the 42 candidate orthologous groups can be identified to have truly one-to-one orthologous relationships, whereas other groups were characterized by one (many)-to-many orthologous relationships or even more complex scenarios involving gene duplications and/or gene losses. The result could imply that the classical one-to-one orthology might be not as common as typically accepted and automated similarity-based methods should be used with caution when accurate orthology/paralogy discrimination is required.

Animals↗

Effect of temperature on dopamine transporter function and intracellular accumulation of methamphetamine: implications for methamphetamine-induced dopaminergic neurotoxicity.

Hyperthermia exacerbates and hypothermia attenuates methamphetamine (METH)-induced dopamine (DA) neurotoxicity. The mechanisms underlying these temperature effects are unknown. Given the essential role of the DA transporter (DAT) in the expression of METH-induced DA neurotoxicity, we hypothesized that the effect of temperature on METH-induced DA neurotoxicity is mediated, at least in part, at the level of the DAT. To test this hypothesis, the effects of small, physiologically relevant temperature changes on DAT function were evaluated in two types of cultured neuronal cells: (1) a neuroblastoma cell line stably transfected with human DAT cDNA and (2) rat embryonic mesencephalic primary cells that naturally express the DAT. Temperatures for studies of DAT function were selected based on core temperature measurements in animals exposed to METH under usual ambient (22 degrees C) and hypothermic (6 degrees C) temperature conditions, where METH neurotoxicity was fully expressed and blocked, respectively. DAT function, determined by measuring accumulation of radiolabeled DA and 1-methyl-4-phenylpyridinium (MPP(+)), was found to directly correlate with temperature, with higher levels of substrate uptake at 40 degrees C, intermediate levels at 37 degrees C, and lower levels at 34 degrees C. DAT-mediated accumulation of METH also directly correlated with temperature, with greater accumulation at higher temperatures. These findings indicate that relatively small, physiologically relevant changes in temperature significantly alter DAT function and intracellular METH accumulation, and suggest that the effect of temperature on METH-induced DA neurotoxicity is mediated, at least in part, at the level of the DAT.

1-Methyl-4-phenylpyridinium↗

A niche maintaining germ line stem cells in the Drosophila ovary.

Stromal cells are thought to generate specific regulatory microenviroments or "niches" that control stem cell behavior. Characterizing stem cell niches in vivo remains an important goal that has been difficult to achieve. The individual ovarioles of the Drosophila ovary each contain about two germ line stem cells that maintain oocyte production. Here we show that anterior ovariolar somatic cells comprising three cell types act as a germ line stem cell niche. Germ line stem cells lost by normal or induced differentiation are efficiently replaced, and the ability to repopulate the niche increases the functional lifetime of ovarioles in vivo. Our studies implicate one of the somatic cell types, the cap cells, as a key niche component.

Animals↗

Disulfide bonds are generated by quinone reduction.

The chemistry of disulfide exchange in biological systems is well studied. However, very little information is available concerning the actual origin of disulfide bonds. Here we show that DsbB, a protein required for disulfide bond formation in vivo, uses the oxidizing power of quinones to generate disulfides de novo. This is a novel catalytic activity, which to our knowledge has not yet been described. This catalytic activity is apparently the major source of disulfides in vivo. We developed a new assay to characterize further this previously undescribed enzymatic activity, and we show that quinones get reduced during the course of the reaction. DsbB contains a single high affinity quinone-binding site. We reconstitute oxidative folding in vitro in the presence of the following components that are necessary in vivo: DsbA, DsbB, and quinone. We show that the oxidative refolding of ribonuclease A is catalyzed by this system in a quinone-dependent manner. The disulfide isomerase DsbC is required to regain ribonuclease activity suggesting that the DsbA-DsbB system introduces at least some non-native disulfide bonds. We show that the oxidative and isomerase systems are kinetically isolated in vitro. This helps explain how the cell avoids oxidative inactivation of the disulfide isomerization pathway.

Bacterial Proteins↗

Enhancement of immunogenicity of tumor cells by cotransfection with genes encoding antisense insulin-like growth factor-1 and B7.1 molecules.

Insulin-like growth factor-1 (IGF-1) is expressed in many tumor cell lines and has a role in both normal cell proliferation and in the growth of cancers. Tumor cells transfected with a vector encoding an IGF-1 antisense cDNA transcriptional cassette driven by the mouse metallothionein-1 promoter become immunogenic and lose their tumorigenicity in syngeneic animals. The enhanced immunogenicity is associated with an up-regulation in the expression of major histocompatibility complex class I molecule on cell surfaces. Blockade of the expression of IGF-1 in tumor cells by the IGF-1 antisense RNA approach is not uniformly effective in the induction of antitumoral protective immunity in low and nonimmunogenic tumor model systems. Here, we report that the immunogenicity of hepa 1-6 hepatoma and SMCC-1 colon carcinoma cells, which are poorly immunogenic and unresponsive to antisense IGF-1 gene transfer, can be induced by cotransfection with genes encoding antisense IGF-1 and mouse B7.1 molecules. The tumor cells modified in this manner become strongly immunogenic and can be used as a cellular vaccine to induce a protective immune response in vivo. Immunization with the transfected tumor cells also results in regression of the established hepa 1-6 hepatoma and SMCC-1 colon cancer. The immunity is tumor-specific and is mediated by CD3+ CD8+ T cells. Cytotoxic T lymphocytes generated in vitro by priming naive spleen cells and in vivo by immunizing mice with the double-transfected tumor cells specifically lysed autologous tumors cells and were effective in adoptive immunotherapy. The data suggest that modification of tumor cells in vitro by cotransfection with genes encoding antisense IGF-1 and B7.1 molecules may open a new avenue for cancer immunogene therapy.

Adjuvants, Immunologic↗

Antisense oligonucleotides complementary to immunoglobulin sequences of BCL-2/immunoglobulin fusion transcript induce apoptosis of t(14;18) lymphoma cells.

Antisense oligodeoxyribonucleotides directed at the bcl-2 translational start site downregulate bcl-2 and inhibit growth of the t(14;18)-positive lymphoma line WSU-FSCCL. Non-specific downregulation of bcl-2 expression is expected to be toxic to normal cells as well. The t(14;18) translocation results in a fusion transcript containing the entire bcl-2 coding sequence with a 3' breakpoint fused to the immunoglobulin J(H) region and the c mu heavy chain. We postulated that these immunoglobulin sequences would be a specific target for downregulation of the fusion gene. Here, we have demonstrated that antisense oligodeoxyribonucleotides targeted to immunoglobulin c(mu) sequences downregulate bcl-2 protein expression and induce apoptosis of WSU-FSCCL cells. Inhibiting growth of malignant cells by targeting non-oncogenic sequences other than breakpoints of fusion transcripts expands the potential for tumour-specific genetic manipulation.

Apoptosis↗