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Biomedical subjects

L Ding

Publications and source records attributed to L Ding.

At least 19 recordsLinked to original sources

Defects in ZnO nanorods prepared by a hydrothermal method.

ZnO nanorod arrays were fabricated using a hydrothermal method. The nanorods were studied by scanning electron microscopy, photoluminescence (PL), time-resolved PL, X-ray photoelectron spectroscopy, and positron annihilation spectroscopy before and after annealing in different environments and at different temperatures. Annealing atmosphere and temperature had significant effects on the PL spectrum, while in all cases the positron diffusion length and PL decay times were increased. We found that, while the defect emission can be significantly reduced by annealing at 200 degrees C, the rods still have large defect concentrations as confirmed by their low positron diffusion length and short PL decay time constants.

Journal Article↗

Depth profiling of charging effect of Si nanocrystals embedded in SiO2: a study of charge diffusion among Si nanocrystals.

Si nanocrystal (nc-Si) embedded in SiO2 thin film is synthesized with low-energy Si ion implantation. Depth profiling of the charging effect of the nc-Si is determined from X-ray photoemission measurement. It is observed that there is a strong correlation between the depth profile of the charging effect and the nc-Si depth distribution. The charging effect is found to decrease with the increase of nc-Si concentration and to vanish when a densely stacked nanocrystal layer is formed. The phenomenon is attributed to the charge diffusion among the nanocrystals. The charge diffusion in the nanocrystal layer may have an important implication for nanocrystal flash memory. When such a layer is used as the charge-storage layer in the memory cells, the stored charges could be lost due to the rapid charge diffusion among the nc-Si if a single defect exists in the tunneling oxide, causing a reliability problem in data retention.

Journal Article↗

Mixtures of glucosamine and chondroitin sulfate reverse fibronectin fragment mediated damage to cartilage more effectively than either agent alone.

OBJECTIVE: To test the effectiveness of glucosamine (GluNH(2))-HCl, chondroitin sulfate (CS) and mixtures in protecting cartilage exposed to fibronectin fragments (Fn-fs), an exposure known to enhance catabolic cytokines and matrix metalloproteinases (MMPs). METHODS: Pharmacologic formulations of GluNH(2) (FCHG49) and CS (TRH122) (Nutramax Laboratories, Inc.) were added at 1, 10 or 100 microg/ml singly or in mixtures to bovine cartilage cultures in serum or serum-free conditions with or without Fn-f. Proteoglycan (PG) release into media and remaining cartilage PG content were measured by dye binding analysis and effects on PG synthesis by assays of 35-sulfate incorporation. Effects on MMP-3 and -13 expression were measured by Western blotting of conditioned media. RESULTS: In serum-free conditions, the agents singly or as mixtures did not block Fn-f mediated matrix degradation. In serum, single agents were weakly effective at 100 microg/ml, while the mixture of each agent at 0.1 microg/ml decreased PG loss by about 50% by day 7 and at 1 microg/ml restored nearly 50% of the PG after 7 days in Fn-f pretreated cartilage. However, both agents singly and as mixtures at 0.1-100 microg/ml decreased MMP release. In serum, the single agents at 1-10 microg/ml weakly reversed Fn-f mediated PG synthesis suppression, while the mixtures were 100% effective at 1 microg/ml. CONCLUSIONS: GluNH(2) and CS act synergistically in reversing damage and promoting repair at concentrations found in plasma after oral ingestion of these agents. Reversal of PG synthesis suppression correlates more with these activities than suppression of MMP-3 or -13 expression.

Animals↗

Ion motion in the rectangular wave quadrupole field and digital operation mode of a quadrupole ion trap mass spectrometer.

A quadrupolar electric field driven by a rectangular wave voltage can be used for mass-selective storage and analysis. The ion motion in such an electric field is derived, and the stability of ions is presented in the a-q diagram that is commonly used for sinusoidal wave quadrupole mass spectrometry in association with the solution of the Mathieu equation. The pseudo-potential well is discussed in an approximation that leads to the relation of secular frequency to operating parameters. A scheme for a digital ion trap mass spectrometer is described, based on this theory. An ion optics simulation was performed to check the theory of resonant ejection, and to prove the feasibility of the mass scan method for a practical ion trap of such geometry.

Journal Article↗

Effects of nitrogen deficiency on photosynthetic traits of maize hybrids released in different years.

BACKGROUND AND AIMS: New maize (Zea mays) hybrids outperformed old ones even at reduced N rates. Understanding the mechanisms of the differences in performance between newer and older hybrids under N deficiency could provide avenues for breeding maize cultivars with large yield under N deficiency, and reduce environmental pollution caused by N fertilizers. METHODS: N deficiency effects on grain weight, plant weight, harvest index, leaf area and photosynthetic traits were studied in the field for six maize hybrids released during the past 50 years to compare their tolerance and to explore their physiological mechanisms. KEY RESULTS: N deficiency decreased grain yield and plant weight in all hybrids, especially in the older hybrids. However, there was no significant difference in harvest index, rate of light-saturated photosynthesis (Psat) 20 d before flowering, leaf area or plant weight at flowering between the N-deficient and control plants of all hybrids. Dry matter production after flowering of the N-deficient plants was significantly lower than that of the control plants in all hybrids, especially in the older hybrids, and was mostly due to differences in the rate of decrease in photosynthetic capacity during this stage. The lower Psat of the older hybrids was not due to stomatal limitation, as there was no significant difference in stomatal conductance (gs) and intercellular CO2 concentration (Ci) between the hybrids. N deficiency accelerated senescence, i.e. decreased chlorophyll and soluble protein contents, after anthesis more for the earlier released hybrids than for the later ones. N deficiency decreased phosphoenolpyruvate carboxylase (PEPCase) activity significantly more in older hybrids than newer hybrids, and affected the maximal efficiency of PSII photochemistry (Fv/Fm) only in the old hybrids and at the late stage. CONCLUSIONS: Compared with older (earlier released) hybrids, newer (later released) hybrids maintained greater plant and grain weight under N deficiency because their photosynthetic capacity decreased more slowly after anthesis, associated with smaller non-stomatal limitations due to maintenance of PEPCase activity, and chlorophyll and soluble protein content.

Carbon Dioxide↗

Estimation of the cortical functional connectivity with the multimodal integration of high-resolution EEG and fMRI data by directed transfer function.

Nowadays, several types of brain imaging device are available to provide images of the functional activity of the cerebral cortex based on hemodynamic, metabolic, or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions communicate with each other. In this study, advanced methods for the estimation of cortical connectivity from combined high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data are presented. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual magnetic resonance images, multidipole source model, and regularized linear inverse source estimates of cortical current density. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) fMRI. We estimate functional cortical connectivity by computing the directed transfer function (DTF) on the estimated cortical current density waveforms in regions of interest (ROIs) on the modeled cortical mantle. The proposed method was able to unveil the direction of the information flow between the cortical regions of interest, as it is directional in nature. Furthermore, this method allows to detect changes in the time course of information flow between cortical regions in different frequency bands. The reliability of these techniques was further demonstrated by elaboration of high-resolution EEG and fMRI signals collected during visually triggered finger movements in four healthy subjects. Connectivity patterns estimated for this task reveal an involvement of right parietal and bilateral premotor and prefrontal cortical areas. This cortical region involvement resembles that revealed in previous studies where visually triggered finger movements were analyzed with the use of separate EEG or fMRI measurements.

Adult↗

Estimation of in vivo human brain-to-skull conductivity ratio from simultaneous extra- and intra-cranial electrical potential recordings.

OBJECTIVE: The present study aims to accurately estimate the in vivo brain-to-skull conductivity ratio by means of cortical imaging technique. Simultaneous extra- and intra-cranial potential recordings induced by subdural current stimulation were analyzed to get the estimation. METHODS: The effective brain-to-skull conductivity ratio was estimated in vivo for 5 epilepsy patients. The estimation was performed using multi-channel simultaneously recorded scalp and cortical electrical potentials during subdural electrical stimulation. The cortical imaging technique was used to compute the inverse cortical potential distribution from the scalp recorded potentials using a 3-shell head volume conductor model. The brain-to-skull conductivity ratio, which leads to the most consistent cortical potential estimates with respect to the direct intra-cranial measurements, is considered to be the effective brain-to-skull conductivity ratio. RESULTS: The present estimation provided consistent results in 5 human subjects studied. The in vivo effective brain-to-skull conductivity ratio ranged from 18 to 34 in the 5 epilepsy patients. CONCLUSIONS: The effective brain-to-skull conductivity ratio can be estimated from simultaneous intra- and extra-cranial potential recordings and the averaged value/standard deviation is 25+/-7. SIGNIFICANCE: The present results provide important experimental data on the brain-to-skull conductivity ratio, which is of significance for accurate brain source localization using piece-wise homogeneous head models.

Algorithms↗

Assessing cortical functional connectivity by linear inverse estimation and directed transfer function: simulations and application to real data.

OBJECTIVE: To test a technique called Directed Transfer Function (DTF) for the estimation of human cortical connectivity, by means of simulation study and human study, using high resolution EEG recordings related to finger movements. METHODS: The method of the Directed Transfer Function (DTF) is a frequency-domain approach, based on a multivariate autoregressive modeling of time series and on the concept of Granger causality. Since the spreading of the potential from the cortex to the sensors makes it difficult to infer the relation between the spatial patterns on the sensor space and those on the cortical sites, we propose the use of the DTF method on cortical signals estimated from high resolution EEG recordings, which exhibit a higher spatial resolution than conventional cerebral electromagnetic measures. The simulation study was followed by an analysis of variance (ANOVA) of the results obtained for different levels of Signal to Noise Ratio (SNR) and temporal length, as they have been systematically imposed on simulated signals. The whole methodology was then applied to high resolution EEG data recorded during a visually paced finger movement. RESULTS: The statistical analysis performed returns that during simulations, DTF is able to estimate correctly the imposed connectivity patterns under reasonable operative conditions, i.e. when data exhibit a SNR of at least 3 and a length of at least 75 s of non-consecutive recordings at 64 Hz of sampling rate, equivalent, more generally, to 4800 data samples. CONCLUSIONS: Functional connectivity patterns of cortical activity can be effectively estimated under general conditions met in any practical EEG recordings, by combining high resolution EEG techniques, linear inverse estimation and the DTF method. SIGNIFICANCE: The estimation of cortical connectivity can be performed not only with hemodynamic measurements, by using functional MRI recordings, but also with modern EEG recordings treated with advanced computational techniques.

Analysis of Variance↗

Development of water-based liquid chromatography at the critical condition.

Liquid chromatography at the critical condition (LCCC) is a chromatographic technique that allows for the isolation of one area of the polymer matrix so that other areas of the polymer may be probed with size-exclusion or adsorptive chromatographic modes. This technique has been successfully applied to the analysis of functionality distributions in functionalized oligomers and to polymer distributions within copolymers. Herein, the critical conditions of two polar polymers, poly(acrylic acid) and polystyrene sulfonate, are determined. These conditions were identified by varying buffer concentration, organic modifier within the mobile phase, or both. At the critical condition of poly(acrylic acid), the retention characteristics of a copolymer of acrylic acid and vinyl pyrrolidinone were determined. This extension to water-based mobile phase conditions will substantially broaden the possible applications of LCCC.

Journal Article↗

Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion.

BACKGROUND: Imiquimod 5% cream has been investigated for non-surgical treatment of superficial and nodular basal cell carcinoma (BCC) tumours. OBJECTIVES: Two studies were conducted to examine the effect of occlusion at low dosing frequencies on the safety and efficacy of topical imiquimod 5% cream for the treatment of superficial and nodular BCC. PATIENTS AND METHODS: Both open-label studies were conducted in Europe. Patients diagnosed with BCC were enrolled into either the superficial (93 patients) or nodular (90 patients) study, depending on the histological confirmation of the patient's tumour subtype. Patients were randomized to one of four groups to apply imiquimod 5% cream 2 or 3 days per week either with or without occlusion. Six weeks following a 6-week treatment period, the entire target tumour area was excised and histologically examined for evidence of residual tumour. RESULTS: In both studies, the highest histologically complete response rate was seen in the 3 days per week with occlusion groups, with complete response rates of 87% and 65% for the superficial and nodular studies, respectively. Occlusion did not have a statistically significant effect on response rate at either dosing frequency. Response rates for superficial and nodular BCC tumours treated 3 days per week without occlusion were 76% and 50%, respectively. CONCLUSIONS: In the superficial study, the complete response rate of 87% in the 3 days per week with occlusion group was similar to that of daily and 5 days per week dosing without occlusion in a previous 12-week study and one study of daily dosing without occlusion for 6 weeks. All treatment groups had acceptable safety profiles in both studies. Occlusion did not have a statistically significant effect on efficacy for either superficial or nodular BCC tumours.

Administration, Cutaneous↗

An avian basal ganglia pathway essential for vocal learning forms a closed topographic loop.

The mammalian basal ganglia-thalamocortical pathway is important for motor control, motor learning, and cognitive functions. It contains parallel, closed loops, at least some of which are organized topographically and in a modular manner. Songbirds have a circuit specialized for vocal learning, the anterior forebrain pathway (AFP), forming a basal ganglia loop with only three stations: the pallial ("cortex-like") lateral magnocellular nucleus of the anterior neostriatum (lMAN), the basal ganglia structure area X, and the medial portion of the dorsolateral thalamic nucleus (DLM). Several properties of this pathway resemble those of its mammalian counterpart, but it is unknown whether all projections in the loop are topographically organized, and if so, whether topography is maintained through the entire loop. After small single- or dual-tracer injections into area X and/or the lMAN of adult zebra finches, we found that the area X to DLM projection is topographically organized, and we confirmed the topography for all other AFP projections. Quantitative analysis suggests maintained topography throughout the loop. To test this directly, we injected different tracers into corresponding areas in lMAN and area X. We found somata retrogradely labeled from lMAN and terminals anterogradely labeled from area X occupying the same region of DLM. Many labeled somata were tightly surrounded by tracer-labeled terminals, indicating the microscopically closed nature of the AFP loop. Thus, like mammals, birds have at least one closed, topographic loop traversing the basal ganglia, thalamus, and pallium. Each such loop could serve as a computational unit for motor or cognitive functions.

Animals↗

Human immunodeficiency virus-seronegative adults with extrapulmonary tuberculosis have abnormal innate immune responses.

Extrapulmonary tuberculosis is presumably a marker of underlying immunodeficiency, but cytokine response pathways in these patients have not been well studied. Cytokine responses of peripheral blood mononuclear cells from human immunodeficiency virus-seronegative adults with prior culture-confirmed extrapulmonary tuberculosis were compared with those of persons with latent Mycobacterium tuberculosis infection. Mitogen-stimulated interferon (IFN)-gamma production, interleukin (IL)-12 production, and IFN-gamma receptor- and IL-12 receptor-mediated cytokine production did not differ between case patients and control patients. However, median resting IL-8 production was significantly lower in case patients than control patients (8051 vs. 19,290 pg/mL; P=.009). In addition, the median tumor necrosis factor (TNF)-alpha response was lower in case patients than control patients after stimulation with lipopolysaccharide (833 vs. 1149 pg/mL; P=.06) and lipopolysaccharide plus IFN-gamma (3301 vs. 4411 pg/mL; P=.04). These abnormalities in resting IL-8 and lipopolysaccharide-induced TNF-alpha production were not associated with IFN-gamma or IL-12 abnormalities and were detected up to several years after cure of disease, suggesting an abnormality in innate immunity.

Case-Control Studies↗

In vivo evaluation of the early events associated with liver metastasis of circulating cancer cells.

The mechanism of metastasis formation remains still largely unknown. Many studies underline the importance and complexity of the initial arrest of the circulating tumour cells in the target organ, a key stage in metastasis occurrence. In our study, we evaluated by visual means the metastasis formation using an in vivo microscopy system in a murine model. Moreover, we investigated the involvement of P-selectin in these processes using immunohistochemistry and P-selectin knockout mice. The present study offers direct evidence of distinct pathways for tumour metastasis formation by a lymphoma cell - EL-4 and a solid tumour cell - C26. Off-line analysis of the images and histological data confirmed that mechanical entrapment of the solid tumour cell, which had a bigger diameter than that of the liver sinusoids, promoted metastasis without any detectable involvement of adhesion molecules. On the other hand, we observed that lymphoma cells, in spite of their smaller diameter as compared to the sinusoids, promoted liver metastasis as well, but with the essential participation in their arrest of P-selectin, indicating an adhesion molecule-mediated pathway.

Adenocarcinoma↗

A selenium-containing catalytic antibody with Type I deiodinase activity.

Acting as a mimic of type I deiodinase (DI), a selenium-containing catalytic antibody (Se-4C5) prepared by converting the serine residues of monoclonal antibody 4C5 raised against thyroxine (T4) into selenocysteines, can catalyze the deiodination of T(4) to 3,5,3'-triiodothyronine (T(3)) with dithiothreitol (DTT) as cosubstrate. Investigations into the deiodinative reaction by Se-4C5 revealed the relationship between the initial velocity and substrate concentration was subjected to Michaelis-Menten equation and the reaction mechanism was ping-pong one. The kinetic properties of the catalytic antibody were a little similar to those of DI, with Km values for T(4) and DTT of approximately 0.8 microM and 1.8 mM, respectively, and V(m) value of 270 pmol per mg protein per min. The activity could be sensitively inhibited by PTU with a Ki value of approximately 120 microM at 2.0 microM of T(4) concentration, revealing that PTU was a competitive inhibitor for DTT.

Amino Acid Substitution↗

Preparation and properties of a selenium-containing catalytic antibody as type I deiodinase mimic.

Conversion of thyroxine (T4) to 3,5,3'-triiodothyronine is an essential first step in controlling thyroid hormone action. Type I deiodinase (DI) can catalyze the conversion to produce the bulk of serum 3,5,3'-triiodothyronine. Acting as a mimic of DI, a selenium-containing catalytic antibody (Se-4C5) prepared by converting the serine residues of monoclonal antibody 4C5 raised against T4 into selenocysteines, can catalyze the deiodination of T4 with dithiothreitol (DTT) as cosubstrate. The mimic enzyme Se-4C5 exhibited a much greater deiodinase activity than model compound ebselen and another selenium-containing antibody Se-Hp4 against GSH. The coupling of selenocysteine with the combining pocket of antibody 4C5 endowed Se-4C5 with enzymatic activity. To probe the catalytic mechanism of the catalytic antibody, detailed kinetic studies were carried out in this paper. Investigations into the deiodinative reaction revealed the relationship between the initial velocity and substrate concentration. The characteristic parallel Dalziel plots demonstrated that Se-4C5-catalyzed reaction mechanism was ping-pong one, involving at least one covalent enzyme intermediate. The kinetic properties of the catalytic antibody were similar to those of DI, with Km values for T4 and DTT of approximately 0.8 microm and 1.8 mm, respectively, and a Vm value of 270 pmol per mg of protein per min. The activity could be sensitively inhibited by 6-propyl-2-thiouracil (PTU) with a K(i) value of approximately 120 microm at 2.0 microm T4 concentration. The PTU inhibition was progressively alleviated with the increasing concentration of added DTT, revealing that PTU was a competitive inhibitor for DTT.

Animals↗

Anti-MUC-1 immunoliposomal doxorubicin in the treatment of murine models of metastatic breast cancer.

The fate of breast cancer patients is dependent upon elimination or control of metastases. We studied the effect of antibody-targeted liposomes containing entrapped doxorubicin (DXR) on development of tumours in two models of breast cancer, pseudometastatic and metastatic, in mice. The former used the mouse mammary carcinoma cell line GZHI, which expresses the human MUC-1 gene (L. Ding, E.N. Lalani, M. Reddish, R. Koganty, T. Wong, J. Samuel, M.B. Yacyshyn, A. Meikle, P.Y.S. Fung, J. Taylor-Papadimitriou, B.M. Longenecker, Cancer Immunol. Immunother. 36 (1993) 9--17). GZHI cells seed into the lungs of Balb/c mice following intravenous injection. The latter used the 4T1-MUC1 cell line, a MUC-1 transfectant of the mouse mammary carcinoma cell line 4T1, which metastasizes from a primary mammary fatpad (mfp) implant to the lungs (C.J. Aslakson, F.R. Miller, Cancer Res. 52 (1992) 1399--1405). B27.29, a monoclonal antibody against the MUC-1 antigen, was used to target sterically stabilized immunoliposomes (SIL[B27.29]) to tumour cells. In vitro, SIL[B27.29] showed high specific binding to both GZHI and 4T1-MUC1 cells. The IC(50) of DXR-loaded SIL[B27.29] was similar to that of free drug for GZHI cells. In the pseudometastatic model, mice treated with a single injection of 6 mg DXR/kg in DXR-SIL[B27.29] at 24 h after cell implantation had longer survival times than those injected with non-targeted liposomal drug. In the metastatic model, severe combined immune deficiency mice given weekly injectionsx3 of 2.5 mg DXR/kg encapsulated in either targeted or non-targeted liposomes were almost equally effective in slowing growth of the primary tumour and reducing development of lung tumours. Surgical removal of the primary tumour from mfp, followed by various chemotherapy regimens, was attempted, but removal of the primary tumour was generally incomplete; tumour regrowth occurred and metastases developed in the lungs in all treatment groups. DXR-SL reduced the occurrence of regrowth of the primary tumour, whereas neither targeted liposomal drug or free drug prevented regrowth. We conclude that monoclonal antibody-targeted liposomal DXR is effective in treating early lesions in both the pseudometastatic and metastatic models, but limitations to the access of the targeted liposomes to tumour cells in the primary tumour compromised their therapeutic efficacy in treating the more advanced lesions.

Animals↗

Barrel-stave model or toroidal model? A case study on melittin pores.

Transmembrane pores induced by amphiphilic peptides, including melittin, are often modeled with the barrel-stave model after the alamethicin pore. We examine this assumption on melittin by using two methods, oriented circular dichroism (OCD) for detecting the orientation of melittin helix and neutron scattering for detecting transmembrane pores. OCD spectra of melittin were systematically measured. Melittin can orient either perpendicularly or parallel to a lipid bilayer, depending on the physical condition and the composition of the bilayer. Transmembrane pores were detected when the helices oriented perpendicularly to the plane of the bilayers, not when the helices oriented parallel to the bilayers. The evidence that led to the barrel-stave model for alamethicin and that to the toroidal model for magainin were reviewed. The properties of melittin pores are closely similar to that of magainin but unlike that of alamethicin. We conclude that, among naturally produced peptides that we have investigated, only alamethicin conforms to the barrel-stave model. Other peptides, including magainins, melittin and protegrins, all appear to induce transmembrane pores that conform to the toroidal model in which the lipid monolayer bends continuously through the pore so that the water core is lined by both the peptides and the lipid headgroups.

Animals↗