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Biomedical subjects

X Luo

Publications and source records attributed to X Luo.

At least 19 recordsLinked to original sources

Endometrial expression of epithelial neutrophil-activating peptide-78 during the menstrual cycle or in progestin-only contraceptive users with breakthrough bleeding and the influence of doxycycline therapy.

BACKGROUND: Endometrial breakthrough bleeding is characterized by an inflammatory reaction and increased production of proinflammatory mediators, one of which may be epithelial neutrophil-activating peptide-78 (ENA-78), a chemokine with neutrophil-activating properties. METHODS AND RESULTS: We therefore investigated the endometrial expression of ENA-78 in Norplant users as progestin-only contraceptive with various bleeding patterns (n=35) as compared with non-users with a normal menstrual cycle (n=55). The endometrial stromal cells (ESCs) were the major site of ENA-78 expression with the highest levels found during the secretory phase. The expression of ENA-78 was increased in Norplant users with irregular bleeding as compared with those with regular cycles and amenorrhoea. The levels of ENA-78 detected in uterine washes and sera after the use of Norplant for 3-6 months (n=25) increased compared with baseline (P < 0.05). These levels did not significantly change in Norplant users who received doxycycline (Dox) therapy (25 mg/twice daily for 6 months) when measured midway through or at the conclusion of study when compared with the baseline (n=25). Treatments with medroxyprogesterone acetate (MPA) and tumour necrosis factor-alpha (TNF-alpha) (25 ng/ml), but not 17beta-estradiol (E2) or E2 + MPA (10(-8) M), representing endometrium exposed to contraceptive and inflammatory conditions, respectively, increased the levels of ENA-78 production by ESCs, and this was reduced by co-treatments with Dox (25 microg/ml) (P < 0.05). CONCLUSIONS: The endometrial production of ENA-78 is altered in progestin-only contraceptive users experiencing breakthrough bleeding and is regulated by MPA and TNF-alpha in ESCs. Although Dox therapy did not alter uterine ENA-78 secretion, its suppression in ESCs suggests that Dox, acting site-specifically and through an anti-inflammatory mechanism, may influence the outcome of breakthrough bleeding in contraceptive users.

Adolescent↗

Predictive factors for prognosis of hilar cholangiocarcinoma: postresection radiotherapy improves survival.

AIMS: Several studies have analyzed the determinants of long-term survival in hilar cholangiocarcinoma (HCCA) patients, but the majority of these have not speculated adjuvant therapy on prognosis. We conduct this study to identify potential predictive factors for prognosis of HCCA focusing on aspects dealing with adjuvant therapy. PATIENTS AND METHODS: Data from 75 consecutive HCCA patients undergoing surgical resection with curative intent were recorded prospectively. The survivals of patients were comparable with respect to different factors followed by a univariate and multivariate analysis. RESULTS: Actual 1-year, 3-year, and 5-year survival rates were 84.0, 44.4 and 12.0%, respectively. By Cox proportional hazards survival analysis, the most powerful predictors of outcome was resection type (Hazard Ratio [HR] 17.4, 95% confidence interval [CI] 16.8-17.8), followed by adjuvant radiotherapy (RT) (HR 4.3, 95% CI 3.6-4.9), regional lymph nodes involvement (HR 2.1, 95% CI 1.7-2.6), and preoperative maximum serum total bilirubin level (HR 2.0, 95% CI 1.5-2.5). CONCLUSIONS: Our study showed overall a highly significant benefit in survival in favor of RT, and the difference was especially significant after R1/R2 resection and in patients with Bismuth III/IV type tumors. Postresection chemotherapy (CTx) did not show any clinical benefits. R0 resection still significantly improves survival. Lower total serum bilirubin level, no regional lymph nodes involvement conferred survival advantage.

Adult↗

Squamous cell carcinoma growth in mice and in culture is regulated by c-Jun and its control of matrix metalloproteinase-2 and -9 expression.

Squamous cell carcinoma (SCC) is an invasive malignancy of epidermal keratinocytes. Surgical excision is currently the main treatment; however, this can cause scarring and disfigurement. There is accordingly, an acute need for alternative strategies to treat SCC. The transcription factor c-Jun is expressed in human SCC and another common form of invasive skin cancer, basal cell carcinoma together with the mitogenic marker-proliferating cell nuclear antigen. Here, we have employed DNAzymes (catalytic DNA molecules) targeting c-Jun (Dz13) to inhibit c-Jun expression in SCC cells. Dz13 inhibits SCC proliferation and suppresses solid SCC tumor growth and tumor angiogenesis in severe combined immunodeficient mice. We further demonstrate that Dz13 inhibits c-Jun, together with matrix metalloproteinase (MMP)-2 and MMP-9 expression in the tumors, consistent with DNAzyme inhibition of MMP-2 and MMP-9 gelatinolytic activity by zymography. Dz13 also suppressed the expression of vascular endothelial growth factor and fibroblast growth factor-2 in the tumors. These findings demonstrate that c-Jun regulates SCC growth and suggest that DNAzymes targeting this transcription factor may potentially be useful as inhibitors of cutaneous carcinoma.

Animals↗

Detecting chaos in pseudoperiodic time series without embedding.

A different method is proposed to detect deterministic structure from a pseudoperiodic time series. By using the correlation coefficient as a measure of the distance between cycles, we are exempt from phase-space reconstruction and further construct a hierarchy of pseudocycle series that, in turn, preserve less determinism than the original time series. Appropriate statistics are then devised to reveal the temporal and spatial correlation encoded in this hierarchy of the pseudocycle series, which allows for a reliable detection of determinism and chaos in the original time series. We demonstrate that this method can reliably identify chaos in the presence of noise of different sources for both artificial data and experimental time series.

Journal Article↗

Opportunities for performance improvement in relation to medication administration during pediatric stabilization.

OBJECTIVES: To identify and characterize areas for improvement in the clinical performance of nurses in relation to medication administration. METHOD: Nurses participated in a simulated pediatric stabilization event which was videotaped. Their clinical performance was evaluated at each of the following steps: (1) communicating and confirming the dose of medication; (2) converting the dose; (3) selecting the correct medications; (4) properly preparing the medication formulation; and (5) measuring medication doses. The time required to convert and draw up the medications was also evaluated. RESULTS: A total of 150 medication orders for five medications were given by the physician. Only 55% of the orders were verbally repeated back by the nurses. Of the 120 orders in which the doses were converted from milligrams to milliliters by nurses, 17 (14.2%) were converted incorrectly and the maximum dose deviation reached 400%. Selection of the wrong medication occurred in 11 of the 150 orders. Dextrose (which requires dilution before being administered to children) was not diluted in 17% of the medication orders and in 12% it was diluted improperly. About 40% of the orders for ceftriaxone (which requires reconstitution) were not properly reconstituted. In 49 (32.7%) of the 150 medication orders that were drawn up in a syringe, the amount measured was not consistent with the stated dose. For some medications, a prolonged time was required by nurses to convert the doses and draw up the medications. CONCLUSIONS: By observing the clinical performance of nurses in a simulated videotaped pediatric stabilization event, we have identified some important areas in need of improvement in each step of the medication administration process. These findings indicate a need for improved education, training, and use of clinical aids or adjuncts for pediatric emergency nurses.

Academic Medical Centers↗

Transcriptional upregulation of PUMA modulates endoplasmic reticulum calcium pool depletion-induced apoptosis via Bax activation.

PUMA, a key mediator of p53-induced apoptosis, is a BH3-only domain proapoptotic protein that localizes to mitochondria and interacts with antiapoptotic Bcl-2 and Bcl-X(L). Recent evidence implicates Bax to be an important mediator of PUMA-activated apoptotic signals. We have previously demonstrated that Bax deficiency significantly affects thapsigargin (TG)-mediated endoplasmic reticulum calcium pool depletion-induced apoptosis. We now present evidence that TG upregulates PUMA expression and that although Bax-deficient cells exhibit resistance to TG, Bax deficiency does not attenuate TG upregulation of PUMA expression. Furthermore, TG transcriptionally upregulates PUMA expression in a p53-independent manner and that PUMA-deficient cells are more resistant to undergo TG-induced apoptosis than the PUMA-proficient counterparts. Thus, our results demonstrate that TG engages PUMA and Bax for full transduction of apoptotic signals and both PUMA and Bax appear to exist in the same TG-activated apoptotic pathway in which PUMA may reside upstream of Bax.

Apoptosis↗

Atom fiber for omnidirectional guiding of cold neutral atoms.

We present an omnidirectional matter waveguide on an atom chip. The guide is based on a combination of two current-carrying wires and a bias field pointing perpendicular to the chip surface. Thermal atoms are guided for more than two complete turns along a 25-mm-long spiral path (with curve radii as short as 200 microm) at various atom-surface distances (35-450 microm). An extension of the scheme for the guiding of Bose-Einstein condensates is outlined.

Journal Article↗

Achievement of ultralow emittance beam in the accelerator test facility damping ring.

For high luminosity in electron-positron linear colliders, it is essential to generate low vertical emittance beams. We report on the smallest vertical emittance achieved in single-bunch-mode operation of the Accelerator Test Facility, which satisfies the requirement of the x-band linear collider. The emittances were measured with a laser-wire beam-profile monitor installed in the damping ring. The bunch length and the momentum spread of the beam were also recorded under the same conditions. The smallest vertical rms emittance measured at low intensity is 4 pm at a beam energy of 1.3 GeV, which corresponds to the normalized emittance of 1.0x1.0(-8) m. It increases by a factor of 1.5 for a bunch intensity of 10(10) electrons. The measured data agreed to the calculation of intrabeam scattering within much better than a factor of 2.

Journal Article↗

Differential regulation of chondrogenic differentiation by the serotonin2B receptor and retinoic acid in the embryonic mouse hindlimb.

Retinoic acid (RA) synthesizing and metabolizing enzymes are coordinately expressed with serotonin 2B (5-HT2B) receptors at sites of epithelial-mesenchymal (E-M) interaction in the mouse embryo (Bhasin et al., 1999). The promoter of the 5-HT2B receptor contains potential RA response element (RAREs) as well as an AP-2 site. Because both retinoid and serotonergic signaling have been implicated in the regulation of chondrogenic differentiation, the present study investigated whether these signals may work together to regulate this morphogenetic process in hindlimb bud micromass cultures. Results indicate that 5-HT promotes [35S]sulfate incorporation (chondrogenic differentiation) by activation of 5-HT2B receptors, which use the mitogen activated protein kinase (p42 MAPK) signal transduction pathway, whereas RA dose-dependently inhibits sulfate incorporation and promotes expression of RARbeta, which could lead to inhibition of p38 MAPK. No evidence was found to support the possibility that RA negatively regulates expression of 5-HT2B receptors. Taken together, these results suggest that 5-HT and RA may act as opposing signals to regulate chondrogenic differentiation in the developing hindlimb, possibly mediated by different MAPK signal transduction pathways.

Animals↗

Use of chemical characteristics to predict the relative bioavailability of supplemental organic manganese sources for broilers.

Twelve organic Mn sources and MnSO4 were evaluated by polarographic analysis and via solubility in buffers (pH 5 and 2) and deionized water. Fractions from solubility tests were evaluated by gel filtration chromatography for structural integrity. Organic Mn sources included five Mn methionine complexes (Mn Met A to Mn Met E), two Mn proteinates (Mn Pro A and Mn Pro B), and five Mn amino acids (Mn AA A to Mn AA E). Sources varied considerably in chemical characteristics. Chelation strength (Qf) ranged from weak (1.9 Qf-values) to strong complexes (115.4 Qf-values). No complexed Mn was found in filtrates at pH 2.0 or 5.0. A 42-d bioassay was used to estimate relative bioavailability of Mn sources for chicks fed diets supplemented with 60, 120, or 180 mg Mn/kg. Bone Mn, heart Mn, heart manganese-superoxide dismutase activity (MnSOD), and heart MnSOD mRNA increased (P < 0.001) as dietary Mn increased. Only heart MnSOD mRNA tended (P < 0.10) to differ among dietary Mn sources. For bioassays of Mn, the MnSOD mRNA level in heart was more sensitive than the MnSOD activity in heart or other indices. Relative to MnSO4 (assigned 100%), slope ratios of MnSOD mRNA levels in heart gave bioavailabilities of 99, 132, and 113% for Mn Met E, Mn AA B, and Mn AA C sources with weak, moderate, and strong chelation strength, respectively. The bioavailability of Mn was more closely related to chelation strength as measured by polarography than to chemical traits assessed by solubility or structural integrity.

Animal Feed↗

Trapping and manipulating neutral atoms with electrostatic fields.

We report on experiments with cold thermal (7)Li atoms confined in combined magnetic and electric potentials. A novel type of three-dimensional trap was formed by modulating a magnetic guide using electrostatic fields. We observed atoms trapped in a string of up to six individual such traps, a controlled transport of an atomic cloud over a distance of 400 microm, and a dynamic splitting of a single trap into a double well potential. Applications for quantum information processing are discussed.

Journal Article↗

Macrophage proteomic fingerprinting predicts HIV-1-associated cognitive impairment.

BACKGROUND: Specific proteins produced from monocytes may be linked to the pathogenesis and aid in the diagnosis of HIV-1-associated dementia (HAD). OBJECTIVE: The authors assessed whether a diagnostic phenomic protein profile could be obtained from monocyte-derived macrophages (MDM) from HIV-1-infected patients with cognitive impairment. METHODS: Twenty-one HIV-1-infected Hispanic women and 10 seronegative controls matched by age and sex were followed at the University of Puerto Rico Medical Sciences Campus, where neuropsychological, immune, and viral parameters were tested. Monocytes were recovered by Percoll gradient centrifugation from peripheral blood mononuclear cells. MDM lysates were prepared after 7 days of cultivation and protein profiles analyzed by surface enhanced laser desorption/ionization (SELDI)-time of flight (TOF) ProteinChip tests. Classification trees were prepared for statistical analyses. RESULTS: A total of 177 protein peaks from 2 to 80 kDa were evaluated in 31 patient MDM lysates by SELDI-TOF ProteinChip assays. Select protein peaks, at 5028 and 4320 Da, separated HIV-1-infected from HIV-1-seronegative subjects with a sensitivity of 100% and a specificity of 80%. Thirty-eight peaks were used to differentiate HIV-1-infected subjects with and without cognitive impairment. A 4348 Da protein separated the two groups with a sensitivity of 100% and a specificity of 75%. CONCLUSIONS: The identification of unique phenomic MDM profiles from cognitively impaired HIV-1-infected patients supports the hypothesis that changes in monocyte function parallel the development of HAD.

AIDS Dementia Complex↗

Reproduction and cytogenetic characterization of interspecific hybrids derived from Cucumis hystrix Chakr. x Cucumis sativus L.

Interspecific hybrids between Cucumis hystrix Chakr. (2n = 2 x = 24) and Cucumis sativus L. (2n = 2 x = 14) were produced by means of F(1) (2n = 19) embryo rescue and subsequent chromosome doubling. The hybridity was confirmed by genomic in situ hybridization (GISH) and chromosome analysis. The amphidiploid (2n = 38) was self-pollinated and backcrossed to cucumber resulting in lines with improved crossability to C. sativus. Examination of shape, stainability, and germination rate of pollen grains and yield as a function of mature fruit set per ten pollinated flowers indicated a tendency for increased fertility in BC(1)S(1) progeny when compared to F(1) and amphidiploid offspring. Cytogenetic characterization of F(1) and amphidiploid progeny was performed. Generally normal meioses produced viable pollen grains, and fertilization resulted in partial fertility restoration in amphidiploid progeny. Chromosome anomalies such as "frying-pan trivalent", chromosome lagging and spindle mis-orientation were also observed. In most of the PMCs of the F(1) diploid hybrid progeny, 19 univalents were observed at diakinesis and MI. In the amphidiploid, more than 90% of the configurations at MI consisted of the predicted 19 bivalents and less than 5% contained multivalents [trivalents (2.3%) + quadrivalents (0.3%)], suggesting the presence of preferential pairing, and a distinctive parental genome as well. The chiasmata observed between homoeologous chromosomes further demonstrated the introgression of the C. hystrix genome into that of C. sativus.

Chimera↗

Extremely low vertical-emittance beam in the accelerator test facility at KEK.

Electron beams with the lowest, normalized transverse emittance recorded so far were produced and confirmed in single-bunch-mode operation of the Accelerator Test Facility at KEK. We established a tuning method of the damping ring which achieves a small vertical dispersion and small x-y orbit coupling. The vertical emittance was less than 1% of the horizontal emittance. At the zero-intensity limit, the vertical normalized emittance was less than 2.8 x 10(-8) rad m at beam energy 1.3 GeV. At high intensity, strong effects of intrabeam scattering were observed, which had been expected in view of the extremely high particle density due to the small transverse emittance.

Journal Article↗

betac cytokine receptor-induced stimulation of cAMP response element binding protein phosphorylation requires protein kinase C in myeloid cells: a novel cytokine signal transduction cascade.

We have recently shown that IL-3R occupancy activates a phosphatidylcholine-specific phospholipase C, and the sustained diacylglycerol accumulation subsequently activates protein kinase C (PKC). In human IL-3-dependent myeloid cells (TF-1), the novel PKCepsilon isoform regulates bcl-2 expression and cell survival. The report of a PKC activatable cAMP response element (CRE) in the bcl-2 promoter and a role for PKC in bcl-2 expression in B cells led us to the hypothesis that PKC phosphorylation activates transcription factor CREB after IL-3R engagement. We found that IL-3 and GM-CSF induced phosphorylation of CREB on Ser(133) in TF-1 cells, and this phosphorylation was blocked by two structurally unrelated classes of PKC inhibitors. An inhibitor of cyclic nucleotide-dependent kinases did not block this phosphorylation. IL-4, which is biologically active in these cells but does not use the beta common subunit, did not phosphorylate CREB on Ser(133). Inhibition of mitogen-activated protein kinase kinase activity also inhibited IL3-induced CREB phosphorylation. The PKC inhibitors, but not a cyclic nucleotide-dependent kinase inhibitor, blocked IL-3 activation of CRE-dependent transcription from an egr-1 promoter/chloramphenicol acetyltransferase (CAT) reporter construction transiently transfected into TF-1 cells. Finally, TF-1 cells stably overexpressing PKCepsilon, but not the delta isoform of PKC, enhanced CRE-dependent CAT expression from the promoter/reporter construction. Therefore, it is likely that a PKCepsilon kinase cascade resulting in CREB phosphorylation represents a novel signal transduction cascade for regulating cellular gene expression through the beta common cytokine receptor.

Amides↗

Polarized expression of G protein-coupled receptors and an all-or-none discharge of Ca2+ pools at initiation sites of [Ca2+]i waves in polarized exocrine cells.

In the present work we examined localization and behavior of G protein-coupled receptors (GPCR) in polarized exocrine cells to address the questions of how luminal to basal Ca(2+) waves can be generated in a receptor-specific manner and whether quantal Ca(2+) release reflects partial release from a continuous pool or an all-or-none release from a compartmentalized pool. Immunolocalization revealed that expression of GPCRs in polarized cells is not uniform, with high levels of GPCR expression at or near the tight junctions. Measurement of phospholipase Cbeta activity and receptor-dependent recruitment and trapping of the box domain of RGS4 in GPCRs complexes indicated autonomous functioning of G(q)-coupled receptors in acinar cells. These findings explain the generation of receptor-specific Ca(2+) waves and why the waves are always initiated at the apical pole. The initiation site of Ca(2+) wave at the apical pole and the pattern of wave propagation were independent of inositol 1,4,5-trisphosphate concentration. Furthermore, a second Ca(2+) wave with the same initiation site and pattern was launched by inhibition of sarco/endoplasmic reticulum Ca(2+)-ATPase pumps of cells continuously stimulated with sub-maximal agonist concentration. By contrast, rapid sequential application of sub-maximal and maximal agonist concentrations to the same cell triggered Ca(2+) waves with different initiation sites. These findings indicate that signaling specificity in pancreatic acinar cells is aided by polarized expression and autonomous functioning of GPCRs and that quantal Ca(2+) release is not due to a partial Ca(2+) release from a continuous pool, but rather, it is due to an all-or-none Ca(2+) release from a compartmentalized Ca(2+) pool.

Animals↗

GRAB: a physiologic guanine nucleotide exchange factor for Rab3A, which interacts with inositol hexakisphosphate kinase.

Diphosphoinositol-pentakisphosphate (InsP7) and bis-diphosphoinositol tetrakisphosphate (InsP8) possess pyrophosphate bonds. InsP7 is formed from inositol hexakisphosphate (InsP6) by recently identified InsP6 kinases designated InsP6K1 and InsP6K2. We now report the identification, cloning, and characterization of a novel protein, GRAB (guanine nucleotide exchange factor for Rab3A), which interacts with both InsP6K1 and Rab3A, a Ras-like GTPase that regulates synaptic vesicle exocytosis. GRAB is a physiologic GEF (guanine nucleotide exchange factor) for Rab3A. Consistent with a role of Rab3A in synaptic vesicle exocytosis, GRAB regulates depolarization-induced release of dopamine from PC12 cells and nicotinic agonist-induced hGH release from bovine adrenal chromaffin cells. The association of InsP6K1 with GRAB fits with a role for InsP7 in vesicle exocytosis.

Adrenal Medulla↗