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Biomedical subjects

Y M Lu

Publications and source records attributed to Y M Lu.

At least 19 recordsLinked to original sources
PubMed2006

Neuronal nitric oxide synthase-derived nitric oxide inhibits neurogenesis in the adult dentate gyrus by down-regulating cyclic AMP response element binding protein phosphorylation.

Neuronal nitric oxide synthase, the major nitric oxide synthase isoform in the mammalian brain, is implicated in some developmental processes, including neuronal survival, precursor proliferation and differentiation. However, reports about the role of neuronal nitric oxide synthase in neurogenesis in the adult dentate gyrus are conflicting. Here we show that 5-bromodeoxyuridine-labeled dividing progenitor cells in the dentate gyrus were significantly increased in mice receiving 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, and in null mutant mice lacking neuronal nitric oxide synthase gene (nNOS-/-) 6 h and 4 weeks after 5-bromodeoxyuridine incorporation. The increase in 5-bromodeoxyuridine positive cells in 7-nitroindazole-treated mice was accompanied by activation of cyclic AMP response element binding protein phosphorylation in the dentate gyrus. Pretreatment with N-methyl-D-aspartate receptor antagonist MK-801 fully abolished the effects of 7-nitroindazole on neurogenesis and cyclic AMP response element binding protein phosphorylation. Furthermore, neuronal nitric oxide synthase inhibition significantly enhanced the survival of newborn cells and the number of 5-bromodeoxyuridine positive/NeuN positive cells in the dentate gyrus. These results indicate that neuronal nitric oxide synthase-derived nitric oxide suppresses neurogenesis in the adult dentate gyrus, in which N-methyl-D-aspartate receptor functions and cyclic AMP response element binding protein phosphorylation may be involved.

Animals↗
PubMed2006

Expression and quantification of LYVE-1 in human colorectal cancer.

The recent discovery of a new hyaluronan (HA) receptor, LYVE-1 (lymphatic vessel endothelial HA receptor), has been received with great interest regarding its specific expression in the lymphatic system. The process of lymphangiogenesis or the formation of new lymphatics in tumours is important because it serves as a major route for cancer metastasis. Therefore, methods to quantify lymphangiogenesis by measuring LYVE-1 have been studied extensively in searching for its possible role in cancer diagnosis, prognosis and even targeted treatment of lymphatic tumour metastasis. Here we report a quantitation study on lymphangiogenesis by either quantitative PCR or immunohistochemistry approaches in detecting LYVE-1 expression in human colorectal tumour. Real-time quantitative polymerase chain reaction (RTQ-PCR) was carried out to quantify LYVE-1 levels in colorectal cancer samples. Also, the same specimen was observed for LYVE-1 expression by immunohistochemical stain. By RTQ-PCR amplification, LYVE-1 was highly expressed in colorectal specimens and LYVE-1 signal from non-cancer tissue of normal control was much weaker by conventional RTPCR. Immunohistochemical stain showed that LYVE-1 was significantly expressed in cancer tissues (especially in the margin region of cancer), whereas in non-cancer specimens fewer positive stains were revealed. The results suggested that the LYVE-1 molecule was expressed significantly in colorectal specimens, which may imply a new marker for a malignant situation.

Base Sequence↗
PubMed2005

Optical properties of ZnO and ZnO:In nanorods assembled by sol-gel method.

Self-assembled zinc oxide (ZnO) and indium-doping zinc oxide (ZnO:In) nanorod thin films were synthesized on quartz substrates without catalyst in aqueous solution by sol-gel method. The samples were characterized by x-ray diffraction (XRD), scanning electron microscope (SEM), Raman-scattering spectroscopy, room-temperature photoluminescence (PL) spectra, and temperature-dependent PL spectra measurements. XRD and Raman spectra illustrated that there were no single In2O3 phase in ZnO lattice after indium doping. The PL spectra of ZnO showed a strong UV emission band located at 394 nm and a very weak visible emission associated with deep-level defects. Indium incorporation induced the shift of optical band gap, quenching of the near-band-edge photoluminescence and enhanced LO mode multiphonon resonant Raman scattering in ZnO crystals at different temperatures. Abnormal temperature dependence of UV emission integrated intensity of ZnO and ZnO:In samples is observed. The local state emission peak of ZnO:In samples at 3.37 eV is observed in low-temperature PL spectra. The near-band-edge emission peak at room temperature was a mixture of excitons and impurity-related transitions for both of two samples.

Journal Article↗
PubMed2005

The optical properties of ZnO hexagonal prisms grown from poly (vinylpyrrolidone)-assisted electrochemical assembly onto Si (111) substrate.

ZnO hexagonal prisms have been grown from poly (vinylpyrrolidone)-assisted electrochemical assembly onto p-type Si (111) substrate. These ZnO prisms arrays are highly (0002) orientated. The (0001) end facets and {1010} side facets of the hexagonal prisms are well defined. The photoluminescence (PL) spectrum of these ZnO prisms shows an intense ultraviolet near band-gap emission with a full width at half maximum of 86 meV at room temperature. The low-temperature PL spectrum is split into well-resolved free and bound exciton emission lines. The temperature dependence of the exciton emission intensities shows a nonmonotonic decaying behavior, which can be explained by the existence of interfacial states.

Journal Article↗
PubMed2005

Effects of thermal annealing on the structural and optical properties of Mg(x)Zn(1-x)O nanocrystals.

Mg(x)Zn(1-x)O ternary alloy nanocrystals with hexagonal wurtzite structures were fabricated by using the sol-gel method. X-ray diffraction patterns, UV-vis absorption spectra, and photoluminescence spectra were used to characterize the structural and optical properties of the nanocrystals. For as-prepared nanocrystals, the band gap increases with increasing Mg content. Weak excitonic emission with strong deep-level emission related to oxygen vacancy and interface defects is observed in the photoluminescence spectra at room temperature. Thermal annealing in oxygen was used to decrease the number of defects and to improve the quality of the nanocrystals. In terms of XRD results, the grain sizes of nanocrystals increase with increasing annealing temperature and the lattice constants of alloy are smaller than those of pure ZnO. The band gap becomes narrower with increasing annealing temperature. For Mg(x)Zn(1-x)O nanocrystals (x=0.03-0.15) annealed at temperatures ranging from 500 to 1000 degrees C, intense near-band-edge (NBE) emissions and weak deep-level (DL) emissions are observed. Consequently, the quality of Mg(x)Zn(1-x)O nanocrystals can be improved by thermal annealing.

Journal Article↗
PubMed2005

Preparation of ZnO colloids by aggregation of the nanocrystal subunits.

Colloidal ZnO particles with narrow size distribution were prepared via a sol-gel process by base-catalyzed hydrolysis of zinc acetate. The morphology of ordered arrays of the particles was recorded by SEM. SEM also reveals that these uniform particles were composed of tiny ZnO subunits (singlets) sized of several nanometers. The size of the singlets, which is confirmed by X-ray diffraction and UV-vis absorption spectra, increases as the aging time is prolonged. The size-selective formation of colloids by aggregation of nanosized subunits is proposed to consist of two-stage growth by nucleation of nanosized crystalline primary particles and their subsequent aggregation into polycrystalline secondary colloids. The aggregates are all spherical because the internal rearrangement processes are fast enough. The ZnO colloids, i.e., the aggregates, tend to self-assemble into well-ordered hexagonal close-packed structures. Room-temperature photoluminescence was characterized for green and aged ZnO.

Journal Article↗
PubMed2005

The effect of surface properties on visible luminescence of nanosized colloidal ZnO membranes.

Luminescence properties of nanosized zinc oxide (ZnO) colloids depend greatly on their surface properties, which are in turn largely determined by the method of preparation. ZnO nanoparticles in the size range from 3 to 9 nm were prepared by addition of tetramethylammonium hydroxide ((CH3)4NOH) to an ethanolic zinc acetate solution. X-ray diffraction (XRD) indicates nanocrystalline ZnO membranes with polycrystalline hexagonal wurtzite structure. The ZnO membranes have a strong visible-emission intensity and the intensity depends upon hydrolysis time. The infrared spectra imply a variety of forms of zinc acetate complexes present on the surface of ZnO particles. The effect of the ZnO membrane surface properties on photoluminescence is discussed.

Journal Article↗
PubMed2004

Spectrum of severe infections in an Asian renal transplant population.

UNLABELLED: Infections in renal transplant recipients (RTX) account for 26% of hospitalization days annually and 40% of overall mortalities. A retrospective study of infections requiring hospitalization occurring among 725 Asian RTX in 2002 was performed. RESULTS: Serious infections requiring at least one hospitalization occurred in 9.2% of RTX (n = 67). Multiple pathogens affected 28.4% of patients, resulting in 118 infectious episodes during 93 hospitalizations. Mean age of affected patients was 48 years and female to male ratio was 2:1. Forty-one (61.2%) had impaired renal function (serum creatinine >141 mumol/L). Mean duration of hospitalization per patient was 17 days and the in-patient mortality rate was 17.9% eighty-one (87%) hospitalizations were for late infections (>6 months posttransplant). Cyclosporine (CsA) with prednisolone with or without azathioprine was the immunosuppressant in 62.7% (n = 42) of RTX but proportionally, infections were more frequent among RTX on other more potent immunosuppressants (n = 21; 7.4% CsA-based vs. 19.3%, potent, P < .05). Bacterial, viral, fungal, and Pneumocystis carinii infections comprised 64.4%, 20.3%, 5.9%, and 4.2% respectively. Urinary tract infection, pneumonia, and bacterial septicemia (35.52%, 31.6%, and 11.8%, respectively) were the major presentations. E. coli, cytomegalovirus (CMV), and Candida were the most common pathogens. Notably, 13 out of 18 (72.2%) viral CMV infections were co- infections, occurring together with bacterial infections. CONCLUSIONS: Late infections with the use of potent immunosuppressives and concurrent CMV reactivation are a major cause of morbidity. Longer antibacterial prophylaxis and closer monitoring for CMV infections may help reduce morbidity.

Asia↗
PubMed2001

Gene targeting reveals a role for the glutamate receptors mGluR5 and GluR2 in learning and memory.

This work suggests that class I mGluRs are involved in long-term potentiation (LTP) at CA1 synapses within the hippocampus. Our data support a pathway linking class I-mGluRs with PKC and src to enhance the open probability of the NMDAR channel. This leads to LTP of the NMDAR, but not the AMPAR. We are currently analyzing double mGluR1 X mGluR5 knockouts with Collingridge for a loss of the LTP induction switch [Nature 368 (1994) 740.]. This induction of LTP of the NMDAR is necessary for "spatial" learning and memory to occur, since mice lacking the mGluR5 are deficient in the Morris water maze and context-dependent fear conditioning. We postulate that AMPARs may provide negative feedback inhibition to the NMDAR. Hence, in null mutants lacking the AMPAR subtype, GluR2, LTP in the CA1 region of hippocampal slices was markedly enhanced (twofold) and non-saturating, whereas neuronal excitability and paired-pulse facilitation were normal. The ninefold increase in Ca(2+) permeability, in response to kainate application, suggests one possible mechanism for enhanced LTP. Enhanced LTP could result from enhanced AMPAR channel conductance or increased recruiting of previously silent synapses. Since the GluR2 null mutants showed reduced exploration and impaired motor coordination, we could make no conclusion about its role in learning and memory. Future work will be directed to inducible deletion of GluR2 only in CA1 after development is complete. These results support the correlation between LTP and learning and memory.

Animals↗
PubMed2001

CAKbeta/Pyk2 kinase is a signaling link for induction of long-term potentiation in CA1 hippocampus.

Long-term potentiation (LTP) is an activity-dependent enhancement of synaptic efficacy, considered a model of learning and memory. The biochemical cascade producing LTP requires activation of Src, which upregulates the function of NMDA receptors (NMDARs), but how Src becomes activated is unknown. Here, we show that the focal adhesion kinase CAKbeta/Pyk2 upregulated NMDAR function by activating Src in CA1 hippocampal neurons. Induction of LTP was prevented by blocking CAKbeta/Pyk2, and administering CAKbeta/Pyk2 intracellularly mimicked and occluded LTP. Tyrosine phosphorylation of CAKbeta/Pyk2 and its association with Src was increased by stimulation that produced LTP. Finally, CAKbeta/Pyk2-stimulated enhancement of synaptic AMPA responses was prevented by blocking NMDARS, chelating intracellular Ca(2+), or blocking Src. Thus, activating CAKbeta/Pyk2 is required for inducing LTP and may depend upon downstream activation of Src to upregulate NMDA receptors.

Animals↗
PubMed2001

Deletion of mitochondrial ATPase inhibitor in the yeast Saccharomyces cerevisiae decreased cellular and mitochondrial ATP levels under non-nutritional conditions and induced a respiration-deficient cell-type.

T(1), a mutant yeast lacking three regulatory proteins of F(1)F(o)ATPase, namely ATPase inhibitor, 9K protein and 15K protein, grew on non-fermentable carbon source at the same rate as normal cells but was less viable when incubated in water. During the incubation, the cellular ATP content decreased rapidly in the T(1) cells but not in normal cells, and respiration-deficient cells appeared among the T(1) cells. The same mutation was also induced in D26 cells lacking only the ATPase inhibitor. Overexpression of the ATPase inhibitor in YC63 cells, which were derived from the D26 strain harboring an expression vector containing the gene of the ATPase inhibitor, prevented the decrease of cellular ATP level and the mutation. Isolated T(1) mitochondria exhibited ATP hydrolysis for maintenance of membrane potential when antimycin A was added to the mitochondrial suspension, while normal and YC63 mitochondria continued to show low hydrolytic activity and low membrane potential. Thus, it is likely that deletion of the ATPase inhibitor induces ATPase activity of F(1)F(o)ATPase to create a dispensable membrane potential under the non-nutritional conditions and that this depletes mitochondrial and cellular ATP. The depletion of mitochondrial ATP in turn leads to occurrence of aberrant DNA in mitochondria.

Adenosine Triphosphate↗
PubMed2001

Transthyretin, thyroxine, and retinol-binding protein in human cerebrospinal fluid: effect of lead exposure.

Transthyretin (TTR), synthesized by the choroid plexus, is proposed to have a role in transport of thyroid hormones in the brain. Our previous studies in animals suggest that sequestration of lead (Pb) in the choroid plexus may lead to a marked decrease in TTR levels in the cerebrospinal fluid (CSF). The objectives of this study were to establish in humans whether TTR and thyroxine (T(4)) are correlated in the CSF, and whether CSF levels of Pb are associated with those of TTR, T(4), and/or retinol-binding protein (RBP). Eighty-two paired CSF and blood/serum samples were collected from patients undergoing clinical diagnosis of CSF chemistry. Results showed that the mean value of CSF concentrations for TTR was 3.33 +/- 1.60 microg/mg of CSF proteins (mean +/- SD, n = 82), for total T(4) (TT(4)) was 1.56 +/- 1.68 ng/mg (n = 82), for RBP was 0.34 +/- 0.19 microg/mg (n = 82), and for Pb was 0.53 +/- 0.69 microg/dl (n = 61 for those above the detection limit). Linear regression analyses revealed that CSF TTR levels were positively associated with those of CSF TT(4) (r = 0.33, p < 0.005). CSF TTR concentrations, however, were inversely associated with CSF Pb concentrations (r = -0.29, p < 0.05). There was an inverse, albeit weak, correlation between CSF TT(4) and CSF Pb concentrations (r = -0.22, p = 0.09). The concentrations of TTR, TT(4), and Pb in the CSF did not vary as the function of their levels in blood or serum, but RBP concentrations in the CSF did correlate to those of serum (r = 0.39, p < 0.0005). Unlike TTR, CSF RBP concentrations were not influenced by PB: These human data are consistent with our earlier observations in animals, which suggest that TTR is required for thyroxine transport in the CSF and that Pb exposure is likely associated with diminished TTR levels in the CSF.

Adolescent↗
PubMed2000

Endogenous Zn(2+) is required for the induction of long-term potentiation at rat hippocampal mossy fiber-CA3 synapses.

The functional role of the abundant Zn(2+) found in some hippocampal synapses has been an enigma. We show here, using N-[6-methoxy-8-quinolyl]-P-toluenesulfonamide (TSQ) staining, that chelatable-Zn(2+) can be removed from hippocampal synaptic boutons using dietary depletion or with Zn(2+) chelators. A chronic dietary deficiency of bouton Zn(2+) resulted in the impairment of long-term potentiation (LTP) at mossy fiber-CA3 synapses. The averaged normalized fEPSP slope 30 min after tetanus was 209 +/- 28% of baseline value in control (mean +/- SEM, n = 10), and 118 +/- 12% in Zn(2+)-deficient rats (mean +/- SEM, n = 12, P < 0.01). In the deficient rats with Zn(2+) supplements, mossy fiber LTP returned to normal levels. The acute depletion of bouton Zn(2+) in the hippocampal slice with membrane-permeable Zn(2+) chelators, dithizone, or diethyldithiocarbamic acid (DEDTC) blocked the induction of mossy fiber LTP. The mean amplitudes of EPSCs after tetanus were 194 +/- 22% of baseline value in control (n = 5), compared to 108 +/- 14% in dithizone (n = 6) and 101 +/- 12% in DEDTC (n = 5). The averaged value of LTP, at the associational commisural fiber-CA3 synapses, was 193 +/- 20% in the control (n = 6), compared to 182 +/- 21% (n = 6, P > 0.1) in the presence of dithizone. The blockade of mossy fiber LTP by dithizone was reversible after washout. In addition, normal LTP could be induced by tetanus if exogenous Zn(2+) was applied immediately following dithizone. Our results indicate that the endogenous Zn(2+) is specifically required for LTP induction at the mossy fiber input into CA3 neurons.

Animals↗
PubMed2000

Calcineurin-mediated LTD of GABAergic inhibition underlies the increased excitability of CA1 neurons associated with LTP.

Coincident pre- and postsynaptic activity generates long-term potentiation (LTP), a possible cellular model of learning and memory. LTP has two components: (1) an increase in the excitatory postsynaptic potential (EPSP), and (2) an increase in the ability of the EPSP to generate a spike (E-S coupling of LTP). We have used pharmacological and genetic approaches to address the molecular nature of E-S coupling in CA1 pyramidal neurons. Blockade of the Ca2+-sensitive phosphatase, calcineurin, prevents induction of E-S coupling without interfering with LTP of the EPSP. Calcineurin produces its effect on E-S coupling by inducing a long-lasting depression (LTD) of the GABA(A)-mediated inhibitory postsynaptic potentials (IPSPs). This LTD of the IPSP was prevented by blockade of NMDA receptors. Thus, the tetanus that elicits NMDA-dependent LTP mediates a coordinately regulated double function. It produces LTP of the EPSP and, concomitantly, LTD of the IPSP that leads to enhancement of E-S coupling.

Animals↗
PubMed2000

Binding of an intrinsic ATPase inhibitor to the F(1)FoATPase in phosphorylating conditions of yeast mitochondria.

Yeast mitochondrial ATP synthase has three regulatory proteins; ATPase inhibitor, 9K protein, and 15K protein. A mutant yeast lacking these three regulatory factors was constructed by gene disruption. Rates of ATP synthesis of both wild-type and the mutant yeast mitochondria decreased with decrease of respiration, while their membrane potential was maintained at 170-160 mV under various respiration rates. When mitochondrial respiration was blocked by antimycin A, the membrane potential of both types of mitochondria was maintained at about 160 mV by ATP hydrolysis. ATP hydrolyzing activity of F(1)FoATPase solubilized from normal mitochondria decreased in proportion to the rate of ATP synthesis, while the activity of the mutant F(1)FoATPase was constant regardless of changes in the rate of phosphorylation. These observations strongly suggest that F(1)FoATPase in the phosphorylating mitochondria is a mixture of two types of enzyme, phosphorylating and non-phosphorylating enzymes, whose ratio is determined by the rate of respiration and that the ATPase inhibitor binds preferentially to the non-phosphorylating enzyme.

Adenosine Triphosphate↗
PubMed2000

Weight-correction formula for maternal serum screening for Down syndrome in Taiwan.

BACKGROUND AND PURPOSE: This study examined the relationship between maternal weight and serum marker concentrations (alpha-fetoprotein [AFP] and human chorionic gonadotropin [hCG]) to develop a weight-correction formula for second-trimester Down syndrome screening in Taiwan. METHODS: We conducted a prospective observational study based on data from 18, 016 pregnant Taiwanese women who participated in a second-trimester Down syndrome screening program at Taiwan Adventist Hospital. The relationship between maternal weight and the multiple of median (MoM) concentrations of serum markers was analyzed using two methods; one involved all the observational data (all point method), while the other involved only the median concentrations at various gestational ages (median regression method). In each method, several statistical approaches were used, including simple-linear, reciprocal, quadratic, and log-transformation linear regression. RESULTS: The correlation between maternal body weight and serum marker concentrations using the all point regression method was very poor, while the median regression method achieved a good fit. The reciprocal regression analysis had the best fit between AFP MoM concentration and maternal weight, while the best fit between hCG MoM concentration and maternal weight was achieved with quadratic regression analysis. CONCLUSION: The present study has developed a race-specific weight-correction formula for Taiwanese women. This formula is expected to be helpful in second-trimester Down syndrome screening programs in Taiwan.

Adolescent↗
PubMed1999

Src potentiation of NMDA receptors in hippocampal and spinal neurons is not mediated by reducing zinc inhibition.

The protein-tyrosine kinase Src is known to potentiate the function of NMDA receptors, which is necessary for the induction of long-term potentiation in the hippocampus. With recombinant receptors composed of NR1-1a/NR2A or NR1-1a/2B subunits, Src reduces voltage-independent inhibition by the divalent cation Zn2+. Thereby the function of recombinant NMDA receptors is potentiated by Src only when the Zn2+ level is sufficient to cause tonic inhibition. Here we investigated whether the Src-induced potentiation of NMDA receptor function in neurons is caused by reducing voltage-independent Zn2+ inhibition. Whereas chelating extracellular Zn2+ blocked the Src-induced potentiation of NR1-1a/2A receptors, we found that Zn2+ chelation did not affect the potentiation of NMDA receptor (NMDAR) currents by Src applied into hippocampal CA1 or CA3 neurons. Moreover, Src did not alter the Zn2+ concentration-inhibition relationship for NMDAR currents in CA1 or CA3 neurons. Also, chelating extracellular Zn2+ did not prevent the upregulation of NMDA single-channel activity by endogenous Src in membrane patches from spinal dorsal horn neurons. Taking these results together we conclude that Src-induced potentiation of NMDAR currents is not mediated by reducing Zn2+ inhibition in hippocampal and dorsal horn neurons.

Animals↗