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Biomedical subjects

L Dong

Publications and source records attributed to L Dong.

At least 19 recordsLinked to original sources

Lateral vibration of a water drop and its motion on a vibrating surface.

The resonant modes of sessile water drops on a hydrophobic substrate subjected to a small-amplitude lateral vibration are investigated using computational fluid dynamic (CFD) modeling. As the substrate is vibrated laterally, its momentum diffuses within the Stokes layer of the drop. Above the Stokes layer, the competition between the inertial and Laplace forces causes the formation of capillary waves on the surface of the drop. In the first part of this paper, the resonant states of water drops are illustrated by investigating the velocity profile and the hydrostatic force using a 3d simulation of the Navier-Stokes equation. The simulation also allows an estimation of the contact angle variation on both sides of the drop. In the second part of the paper, we investigate the effect of vibration on a water drop in contact with a vertical plate. Here, as the plate vibrates parallel to gravity, the contact line oscillates. Each oscillation is, however, rectified by hysteresis, thus inducing a ratcheting motion to the water droplet vertically downward. Maximum rectification occurs at the resonant states of the drop. A comparison between the frequency-dependent motion of these drops and the variation of contact angles on their both sides is made. The paper ends with a discussion on the movements of the drops on a horizontal hydrophobic surface subjected to an asymmetric vibration.

Computer Simulation↗

Adenoviral-mediated interferon alpha overcomes resistance to the interferon protein in various cancer types and has marked bystander effects.

We have previously shown that intravesical administration of adenovirus encoding human interferon alpha-2b (Ad-IFN) induced a marked regression of superficial human bladder tumors derived from cells that are resistant to over 1 million units/ml of IFNalpha protein in vitro. In addition, Ad-IFN appeared to produce strong bystander effects. In this study, we show that Ad-IFN causes marked inhibition of cell growth and apoptosis in cells of various tumor types, all of which are resistant to IFNalpha protein. In addition, strong perinuclear IFN staining was seen in all cell lines following Ad-IFN transfection and was never observed after exposure to the IFN protein. Ad-IFN induced proteolytic processing of caspases 3, 8 and 9, indicative of enzymatic activation. However, the caspase-8-selective inhibitor, IETDfmk, blocked apoptosis only in the cell lines that were sensitive to the IFNalpha protein and had minimal effect on Ad-IFN-induced caspase-3 or -9 processing and cell death, indicating that death receptor-independent mechanism(s) were involved in the cytotoxic effects observed for cancer cell lines resistant to the IFNalpha protein. Moreover, we document that a yet to be identified soluble factor(s) is responsible for causing the bystander effect observed following Ad-IFN treatment in IFN protein-resistant cancer cells.

Adenoviridae↗

Preclinical assessment of the feasibility of applying controlled release oral drug delivery to a lead series of atypical antipsychotics.

In this paper, we present a preclinical approach for evaluating the feasibility of applying controlled-release (CR) oral drug delivery to increase the duration of exposure and lower the C(max) of compounds in a lead series of short half-life atypical antipsychotics. Three lead compounds in the series had demonstrated potential pharmacological benefits for the treatment of psychosis, in preclinical studies. However, the compounds showed evidence of insufficient half-lives to enable a once-a-day (QD) product using immediate-release (IR) oral delivery. To evaluate and compare the potential for oral CR delivery to extend the duration of action and thereby enable QD administration, the in vitro solubility and permeability, and the duodenal and colonic absorption of three compounds in the series were measured. Based on the results, one candidate was selected for advancement that showed moderate in vitro solubility, but had the highest in vitro permeability and ratio of colonic to duodenal bioavailability (0.9) in the rat. The results from this study provided evidence that a CR drug delivery system could be used to extend the duration of exposure of the compounds in the series and a scientific basis for selecting one of the three compounds as a candidate.

Administration, Oral↗

Recovery from neutropenia can be predicted by the immature reticulocyte fraction several days before neutrophil recovery in autologous stem cell transplant recipients.

The duration of neutropenia (absolute neutrophil count (ANC) < or = 100/microl) identifies cancer patients at risk for infection. A test that precedes ANC > or = 100/microl would be of clinical value. The immature reticulocyte fraction (IRF) reflects erythroid engraftment and hence a recovering marrow. We evaluated the IRF as predictor of marrow recovery among 90 myeloma patients undergoing their first and second (75 patients) melphalan-based autologous stem cell transplantation (Mel-ASCT). The time to IRF doubling (IRF-D) preceded ANC > or = 100/microl in 99% of patients after the first Mel-ASCT by (mean+/-s.d.) 4.23+/-1.96 days and in 97% of the patients after the second Mel-ASCT by 4.11+/-1.95 days. We validated these findings in a group of 117 myeloma patients and 99 patients with various disorders undergoing ASCT with different conditioning regimens. We also compared the time to hypophosphatemia and to absolute monocyte count > or = 100/microl to the time to ANC > or = 100/microl. These markers were reached prior to this ANC end point in 55 and 25% of patients but were almost always preceded by IRF-D. We conclude that the IRF-D is a simple, inexpensive and widely available test that can predict marrow recovery several days before ANC> or = 100/microl.

Cohort Studies↗

Iron overload is a major risk factor for severe infection after autologous stem cell transplantation: a study of 367 myeloma patients.

We evaluated the risk factors for infection of 367 consecutive myeloma patients who underwent high-dose melphalan and autologous stem cell transplantation (ASCT). Examination of bone marrow iron stores (BMIS) prior to ASCT was used to evaluate body iron stores. Other variables included age, sex, active smoking, myeloma remission status, severity of mucositis and duration of severe neutropenia post-ASCT (<100 absolute neutrophils counts (ANC)/microl). Median age was 56 years; 61% of patients were males. 140 episodes of severe infections occurred in 116 patients, including bacteremia (73), pneumonia (40), severe colitis (25) and bacteremia with septic shock (two). The infection incidence per 1,000 days at risk was 45.2. Pre-ASCT risk factors for severe infection by univariate analysis were increased BMIS (OR=2.686; 95% CI 1.707-4.226; P<0.0001), smoking (OR=1.565; 95% CI 1.005-2.437; P=0.0474) and male gender (OR=1.624; 95% CI 1.019-2.589; P=0.0414). Increased BMIS (OR=2.716; 95% CI 1.720-4.287; P<0.0001) and smoking (OR=1.714; 95% CI 1.081-2.718; P=0.022) remained significant by multivariate analysis. Duration of ANC <100 micro/l (OR=1.129; 95% CI 1.039-1.226; P=0.0069 and OR=1.127; 95% CI 1.038-1.224; P=0.0045 by both univariate and multivariate analysis, respectively) was the only post-ASCT risk factor for infection. Increased pre-transplant BMIS and smoking are significant predictors of severe infection after myeloablative chemotherapy followed by ASCT in myeloma patients.

Analysis of Variance↗

Oral mucositis in myeloma patients undergoing melphalan-based autologous stem cell transplantation: incidence, risk factors and a severity predictive model.

Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.

Adult↗

Lipoxin A4 inhibits connective tissue growth factor-induced production of chemokines in rat mesangial cells.

Connective tissue growth factor (CTGF) is involved in mitogenesis, matrix production, and chemotaxis in mesenchymal cells. The effects of CTGF on the production of chemokines remain unclear. The present studies investigate the regulatory role of CTGF in the production of fractalkine, monocyte chemoattractant protein-1 (MCP-1), and RANTES (regulated upon activation, normal T cell expressed and secreted) in cultured mesangial cells of rats, and the modulatory effects of lipoxin A(4) (LXA(4)) on actions of CTGF. CTGF enhanced the mRNA expression and protein release of fractalkine, MCP-1, and RANTES, the expression of phospho (P)-p42/44 mitogen-activated protein kinase (MAPK), P-phosphoinositide 3-kinase (PI3-K), P-Akt, and activity of nuclear factor-kappaB (NF-kappaB) in mesangial cells. P-p42/44 MAPK blockade inhibited the CTGF-induced expression of P-p42/44 MAPK but not NF-kappaB, and partially decreased the levels of the above chemokines in supernatants. P-PI3-K blockade downregulated the CTGF-stimulated expression of P-PI3-K, P-Akt, and NF-kappaB but not P-p42/44 MAPK, and partially decreased the release of the above chemokines. NF-kappaB blockade abrogated the CTGF-activated NF-kappaB and partially decreased the secretion of the above chemokines. LXA(4) dose-dependently inhibited the CTGF-stimulated mRNA expression and protein release of the above chemokines, and the expression of P-p42/44MAPK, P-PI3-K, P-Akt, and NF-kappaB. In conclusion, these results demonstrate that CTGF induces production of fractalkine, MCP-1, and RANTES via the p42/44 MAPK-, PI3-K/Akt-, and NF-kappaB-dependent signal pathway, and LXA(4) downregulates the above effects of CTGF on rat mesangial cells.

Animals↗

Genetic association of the human corticotropin releasing hormone receptor 1 (CRHR1) with binge drinking and alcohol intake patterns in two independent samples.

To investigate the role of the corticotropin releasing hormone receptor 1 (CRHR1) in patterns of human alcohol drinking and its potential contribution to alcohol dependence, we analysed two independent samples: a sample of adolescents, which consisted of individuals from the 'Mannheim Study of Risk Children' (MARC), who had little previous exposure to alcohol, and a sample of alcohol-dependent adults, who met DSM-IV criteria of alcohol dependence. Following determination of allelic frequencies of 14 polymorphisms of the CRHR1 gene, two haplotype tagging (ht)SNPs discriminating between haplotypes with a frequency of > or =0.7% were identified. Both samples were genotyped and systematically examined for association with the htSNPs of CRHR1. In the adolescent sample, significant group differences between genotypes were observed in binge drinking, lifetime prevalence of alcohol intake and lifetime prevalence of drunkenness. The sample of adult alcohol-dependent patients showed association of CRHR1 with high amount of drinking. This is the first time that an association of CRHR1 with specific patterns of alcohol consumption has been reported. Our findings support results from animal models, suggesting an importance of CRHR1 in integrating gene-environment effects in alcohol use disorders.

Adolescent↗

A flattening filter free photon treatment concept evaluation with Monte Carlo.

In principle, the concept of flat initial radiation-dose distribution across the beam is unnecessary for intensity modulated radiation therapy. Dynamic leaf positioning during irradiation could appropriately adjust the fluence distribution of an unflattened beam that is peaked in the center and deliver the desired uniform or nonuniform dose distribution. Removing the flattening filter could lead to reduced treatment time through higher dose rates and reduced scatter, because there would be substantially less material in the beam; and possibly other dosimetric and clinical advantages. This work aims to evaluate the properties of a flattening filter free clinical accelerator and to investigate its possible advantages in clinical intensity modulated radiation therapy applications by simulating a Varian 2100-based treatment delivery system with Monte Carlo techniques. Several depth-dose curves and lateral dose distribution profiles have been created for various field sizes, with and without the flattening filter. Data computed with this model were used to evaluate the overall quality of such a system in terms of changes in dose rate, photon and electron fluence, and reduction in out-of-field stray dose from the scattered components and were compared to the corresponding data for a standard treatment head with a flattening filter. The results of the simulations of the flattening filter free system show that a substantial increase in dose rate can be achieved, which would reduce the beam on time and decrease the out-of-field dose for patients due to reduced head-leakage dose. Also close to the treatment field edge, a significant improvement in out-of-field dose could be observed for small fields, which can be attributed to the change in the photon spectra, when the flattening filter is removed from the beamline.

Journal Article↗

Quantitative imaging of proteoglycan in cartilage using a gadolinium probe and microCT.

OBJECTIVE: Micro-computed tomography (microCT) imaging has the potential to allow the three-dimensional (3D) visualization of cartilage morphology. However, cartilage intensity on a microCT image is weak because cartilage does not strongly attenuate X-rays. This work was designed to demonstrate that exposure of cartilage to charged gadolinium compounds modifies the intensity to allow an improved visualization of cartilage morphology and the determination of proteoglycan content. DESIGN: Trypsin was used to deplete proteoglycan in bovine nasal cartilage disks. Disks were then exposed to Gd(3+), gadopentetate (Gd-DTPA(2-)), or gadoteridol (Gd-HP-DO3A), and imaged with microCT. The intensities of the disks were measured from the images and compared to the actual proteoglycan content determined with a dimethylmethylene blue assay. RESULTS: Treatment of naïve disks with 200 mM Gd(3+) for 24h at room temperature produced a 2.8-fold increase in intensity on microCT images. Similar treatment with 200 mM Gd-DTPA(2-) produced a 1.4-fold increase. After 2h of trypsin treatment at room temperature, the intensities of cartilage disks exposed to 20 0mM Gd(3+) decreased by 12%. Conversely, the intensities of trypsin-treated disks exposed to 200 mM Gd-DPTA(2-) increased by 15%. Trypsin treatment caused a 4% increase in the intensities of disks exposed to neutral Gd-HP-DO3A. The correlation between proteoglycan content and the microCT intensity of cartilage treated with Gd(3+) was very good (r(2)=0.81). CONCLUSIONS: Gadolinium and microCT allow an improved 3D visualization of cartilage and quantification of its proteoglycan content.

Animals↗

Spectral representation of the effective dielectric constant of graded composites.

We generalize the Bergman-Milton spectral representation, originally derived for a two-component composite, to extract the spectral density function for the effective dielectric constant of a graded composite. This work has been motivated by a recent study of the optical absorption spectrum of a graded metallic film [Huang and Yu, Appl. Phys. Lett. 85, 94 (2004)] in which a broad surface-plasmon absorption band was shown to be responsible for enhanced nonlinear optical response and an attractive figure of merit. It turns out that, unlike in the case of homogeneous constituent components, the characteristic function of a graded composite is a continuous function because of the continuous variation of the dielectric function within the constituent components. Analytical generalization to three-dimensional graded composites is discussed, and numerical calculations for multilayer composites are given as a simple application.

Journal Article↗

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↗

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↗

Leaving previously implanted central venous catheters (ports) in place does not increase morbidity in patients undergoing autologous peripheral stem cell transplantation.

We sought to assess if leaving in place a previously inserted noncolonized or infected implantable catheter (IC) is associated with an increase in morbidity in patients undergoing autologous peripheral stem cell transplantation (APSCT). Medical records from all patients between March 1997 and January 2002 undergoing APSCT with an IC in place were reviewed. Case group (IC in place) was compared with a control group (no IC) from 6 days prior to 60 days after APSCT. In all, 43 cases were matched with 43 controls by underlying disease, age and sex. In both groups, duration of neutropenia and use of antimicrobial prophylaxis were comparable. Underlying malignancies were lymphoma (22/24), multiple myeloma (14/12), leukemia (3/3), and others (7/7) in case and control groups. Cases and controls had comparable rates of risk for fever, bloodstream infection, use of vancomycin and amphotericin B, and death, as well as comparable lengths of stay and readmissions. ICs were used in 20 of 43 patients. Using the IC did not significantly increase the risk of fever, bloodstream infection, length of stay, and/or readmissions after APSCT but was associated with increased use of antibacterial and antifungal agents. Leaving in place a previously inserted, noncolonized or infected IC did not increase morbidity in patients undergoing APSCT.

Adult↗

Serial measurement of serum C-reactive protein levels can identify patients at risk for severe complications following autologous stem cell transplantation.

The value of serum C-reactive protein (CRP) levels as a predictor of complications in neutropenic patients needs to be further defined. We sought to identify an association between severe complications and daily CRP levels measured in 104 multiple myeloma patients during the 3 week period following high-dose melphalan and autologous transplant. Significantly higher mean CRP levels and CRP velocity of increase were observed among patients with severe complications. A cut-off point of 100 mg/l (CRP levels) and 15 mg/l/day (CRP velocity) identified patients likely to suffer severe complications with 86 and 75% sensitivity, respectively. Prospective validation of this model is currently underway.

C-Reactive Protein↗

Electrokinetic behavior of two touching inhomogeneous biological cells and colloidal particles: effects of multipolar interactions.

We present a theory to investigate electrokinetic behavior, namely, electrorotation and dielectrophoresis under alternating current (ac) applied fields for a pair of touching inhomogeneous colloidal particles and biological cells. These inhomogeneous particles are treated as graded ones with physically motivated model dielectric and conductivity profiles. The mutual polarization interaction between the particles yields a change in their respective dipole moments, and hence in the ac electrokinetic spectra. The multipolar interactions between polarized particles are accurately captured by the multiple images method. In the point-dipole limit, our theory reproduces the known results. We find that the multipolar interactions as well as the spatial fluctuations inside the particles can affect the ac electrokinetic spectra significantly.

Biophysics↗

Electroacupuncture for tension-type headache on distal acupoints only: a randomized, controlled, crossover trial.

OBJECTIVE: To investigate the efficacy of electroacupuncture, applied to distal acupoints only, for tension-type headache. BACKGROUND: Electroacupuncture is commonly used for tension-type headache, but when applied to distal acupoints only, evidence of its efficacy is lacking. DESIGN: A randomized, single-blinded, sham-controlled, crossover clinical trial. Methods.-The trial had 5 stages: baseline (2 weeks), phases I and II (each 4 weeks), washout period (2 weeks), and follow-up (3 months after phase II). Forty patients were randomly assigned to either group A or group B. Group A received real electroacupuncture during phase I, then sham electroacupuncture in phase II. Group B received the treatments in reverse order. Outcome measures were headache frequency and duration, pain intensity using a visual analog scale, mechanical pain threshold, headache disability, and sickness impact. Data were analyzed by univariate 2-way analysis of variance. RESULTS: Thirty-seven patients completed the trial. There were no significant differences between the 2 groups at baseline. At the end of phase I, group A, but not group B, demonstrated significant improvement in mean (standard error of the mean [SEM]) headache frequency (3.0 per month [0.3] versus 12.0 per month [1.7]), duration (13.3 hours [3.5] versus 32.0 hours [6.2]), pain intensity (32.8 mm [4.1] versus 47.5 mm [2.7]), pain threshold (right side, 2.9 kg/second [0.1] versus 0.9 kg/second [0.1]; left side, 2.4 kg/second [0.1] versus 1.1 kg/second [0.1]), headache disability score (6.0 [1.0] versus 16.3 [1.6]), and sickness impact score (288.7 [48.0] versus 687.1 [77.2]). For each parameter, significant differences also were demonstrated for both groups between baseline and phase II, and baseline and follow-up. There were no significant differences between the groups at the end of follow-up (P >.05). CONCLUSION: Electroacupuncture to distal points alone is effective for short-term symptomatic relief of tension-type headache.

Acupuncture Points↗

Dielectrophoresis of charged colloidal suspensions.

We present a theoretical study of dielectrophoretic (DEP) crossover spectrum of two polarizable particles under the action of a nonuniform ac electric field. For two approaching particles, the mutual polarization interaction yields a change in their respective dipole moments, and hence, in the DEP crossover spectrum. The induced polarization effects are captured by the multiple image method. Using spectral representation theory, an analytic expression for the DEP force is derived. We find that the mutual polarization effects can change the crossover frequency at which the DEP force changes sign. The results are found to be in agreement with recent experimental observation and as they go beyond the standard theory, they help to clarify the important question of the underlying polarization mechanisms.

Journal Article↗