Biomedical subjects

M Ding

Publications and source records attributed to M Ding.

At least 19 recordsLinked to original sources

PubMed2003

A comparative dosimetric study on tangential photon beams, intensity-modulated radiation therapy (IMRT) and modulated electron radiotherapy (MERT) for breast cancer treatment.

Recently, energy- and intensity-modulated electron radiotherapy (MERT) has garnered a growing interest for the treatment of superficial targets. In this work. we carried out a comparative dosimetry study to evaluate MERT, photon beam intensity-modulated radiation therapy (IMRT) and conventional tangential photon beams for the treatment of breast cancer. A Monte Carlo based treatment planning system has been investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We have compared breast treatment plans generated using this home-grown treatment optimization and dose calculation software forthese treatment techniques. The MERT plans were planned with up to two gantry angles and four nominal energies (6, 9, 12 and 16 MeV). The tangential photon treatment plans were planned with 6 MV wedged photon beams. The IMRT plans were planned using both multiple-gantry 6 MV photon beams or two 6 MV tangential beams. Our results show that tangential IMRT can reduce the dose to the lung, heart and contralateral breast compared to conventional tangential wedged beams (up to 50% reduction in high dose volume or 5 Gy in the maximum dose). MERT can reduce the maximum dose to the lung by up to 20 Gy and to the heart by up to 35 Gy compared to conventional tangential wedged beams. Multiple beam angle IMRT can significantly reduce the maximum dose to the lung and heart (up to 20 Gy) but it induces low and medium doses to a large volume of normal tissues including lung, heart and contralateral breast. It is concluded that MERT has superior capabilities to achieve dose conformity both laterally and in the depth direction, which will be well suited for treating superficial targets such as breast cancer.

Breast Neoplasms↗

PubMed2003

Reduced mechanical load decreases the density, stiffness, and strength of cancellous bone of the mandibular condyle.

OBJECTIVE: To investigate the influence of decreased mechanical loading on the density and mechanical properties of the cancellous bone of the human mandibular condyle. DESIGN: Destructive compressive mechanical tests were performed on cancellous bone specimens.Background. Reduced masticatory function in edentate people leads to a reduction of forces acting on the mandible. As bone reacts to its mechanical environment a change in its material properties can be expected. METHODS: Cylindrical bone specimens were obtained from dentate and edentate embalmed cadavers. Mechanical parameters were determined in the axial and in the transverse directions. Subsequently, density parameters were determined according to a method based on Archimedes' principle. RESULTS: The apparent density and volume fraction of the bone were about 18% lower in the edentate group; no age-related effect on density was found. The decrease of bone in the edentate group was associated with a lower stiffness and strength (about 22% and 28%, respectively). The ultimate strain, however, did not differ between the two groups. Both groups had similar mechanical anisotropy; in axial loading the bone was stiffer and stronger than in transverse loading. CONCLUSIONS: Reduced mechanical load had affected the density and herewith the mechanical properties of condylar cancellous bone, but not its anisotropy. RELEVANCE: The change in material properties of the cancellous bone after loss of teeth indicate that the mandibular condyle is sensitive for changes in its mechanical environment. Therefore, changes in mechanical loading of the condyle have to be accounted for in surgical procedures of the mandible.

Aged↗

PubMed2003

Particle selection for laser-accelerated proton therapy feasibility study.

In this paper we present calculations for the design of a particle selection system for laser-accelerated proton therapy. Laser-accelerated protons coming from a thin high-density foil have broad energy and angular spectra leading to dose distributions that cannot be directly used for therapeutic applications. Our solution to this problem is a compact particle selection and collimation device that delivers small pencil beams of protons with desired energy spectra. We propose a spectrometer-like particle selection and beam modulation system in which the magnetic field will be used to spread the protons spatially according to their energies and emitting angles. Subsequently, an aperture will be used to select the protons within a therapeutic window of energy (energy modulation). It will be shown that for the effective proton spatial differentiation, the primary collimation device should be used, which will collimate protons to the desired angular distribution and limit the spatial mixing of different energy protons once they have traveled through the magnetic system. Due to the angular proton distribution, the spatial mixing of protons of different energies will always be present and it will result in a proton energy spread with the width depending on the energy. For 250 MeV protons, the width (from the maximum to the minimum energy) is found to be 50 MeV for the magnetic field configuration used in our calculations. As the proton energy decreases, its energy width decreases as well, and for 80 MeV protons it equals 9 MeV. The presence of the energy width in the proton energy distribution will modify the depth dose curves needed for the energy modulation calculation. The matching magnetic field setup will ensure the refocusing of the selected protons and the final beam will be collimated by the secondary collimator. The calculations presented in this article show that the dose rate that the selection system can yield is on the order of D=260 Gy/min for a field size of 1 x 1 cm2.

Equipment Design↗

PubMed2003

Changes in the three-dimensional microstructure of human tibial cancellous bone in early osteoarthritis.

We obtained medial and lateral subchondral cancellous bone specimens from ten human post-mortem proximal tibiae with early osteoarthritis (OA) and ten normal age- and gender-matched proximal tibiae. The specimens were scanned by micro-CT and the three-dimensional microstructural properties were quantified. Medial OA cancellous bone was significantly thicker and markedly plate-like, but lower in mechanical properties than normal bone. Similar microstructural changes were also observed for the lateral specimens from OA bone, although there had been no sign of cartilage damage. The increased trabecular thickness and density, but relatively decreased connectivity suggest a mechanism of bone remodelling in early OA as a process of filling trabecular cavities. This process leads to a progressive change of trabeculae from rod-like to plate-like, the opposite to that of normal ageing. The decreased mechanical properties of subchondral cancellous bone in OA, which are due to deterioration in architecture and density, indicate poor bone quality.

Aged↗

PubMed2002

Measurement of the beam-helicity asymmetry in the p((-->)e,e'p)pi(0) reaction at the energy of the Delta(1232) resonance.

In a p((-->)e,e'p)pi(0) out-of-plane coincidence experiment at the three-spectrometer setup of the Mainz Microtron MAMI, the beam-helicity asymmetry has been precisely measured around the energy of the Delta(1232) resonance and Q(2) = 0.2(GeV/c)(2). The results are in disagreement with three up-to-date model calculations. This is interpreted as a lack of understanding of the nonresonant background, which in dynamical models is related to the pion cloud.

Journal Article↗

PubMed2002

Effects of short-term alendronate treatment on the three-dimensional microstructural, physical, and mechanical properties of dog trabecular bone.

The bisphosphonate, alendronate, is well known for its potent inhibition of osteoclast-mediated bone resorption. It has been used clinically for the treatment of osteoporosis and has also recently been used to reduce osteolysis around prostheses in a canine revision model of implant loosening (femoral condyle). In this study, the effects of alendronate on trabecular bone properties were assessed in dogs at an oral dose of 0.5 mg/kg per day over a 12 week period, and compared with control dogs. Cubic cancellous bone specimens were produced from lumbar vertebrae (L-1 and L-2) and bilateral proximal humeri. These specimens were scanned using a high-resolution microcomputed tomography (micro-CT) system. From accurate data sets, three-dimensional microstructural properties were calculated and physical and mechanical properties were determined. Treatment with alendronate increased bone volume fraction by 9.5%, 7.7%, 7.4%, and 18.4%, respectively, in L-1, L-2, humeral greater tuberosity, and humeral head trabecular bone. In the lumbar vertebrae, the alendronate-treated trabeculae were thicker and lower in bone surface-to-volume ratio. In the greater tuberosity, the alendronate-treated trabeculae were thicker, lower in bone surface-to-volume ratio, and less anisotropic. In the humeral head, the alendronate-treated trabeculae were thicker, less anisotropic, lower in surface density, and showed decreased trabecular separation. Alendronate significantly increased apparent density and collagen density in the lumbar vertebrae and humeral heads, and significantly decreased collagen concentration in the vertebrae. In the lumbar vertebrae, Young's modulus in the cephalocaudal direction, ultimate stress, and failure energy were significantly increased in the alendronate-treated group. The changes in mechanical properties in the humeral head trabecular bone were similar to those seen in the lumbar vertebrae. Our results demonstrate that alendronate increases the mechanical properties of healthy canine trabecular bone after short-term treatment. The physical and microstructural changes of trabecular bone are consistent with the significantly increased mechanical properties.

Alendronate↗

PubMed2002

Influence of hyperthyroidism on rat lung cytokine production and nuclear factor-kappaB activation following ozone exposure.

Results from previous studies indicate that hyperthyroidism increases the risk of ozone-induced lung toxicity. To better understand the processes that might contribute to the increased pulmonary inflammatory response to ozone in hyperthyroidism, we evaluated bronchoalveolar lavage fluid levels of selected cytokines in control and hyperthyroid rats after exposure to air or ozone. In addition, we assessed whether there is a relative increase in nuclear factor-kappa B (NF-kappaB) binding activity in cells harvested by bronchoalveolar lavage from hyperthyroid rats following the inhalation of ozone. A hyperthyroid condition was induced by the administration of thyroxine (0.5 mg/kg body weight) for 7 days. Control rats received vehicle injections. The animals were then exposed by inhalation to air or ozone (2 ppm for 3 h) and studied 18 h following the exposure. Bronchoalveolar lavage levels of MIP-2 and MCP-1 were increased in both control and hyperthyroid rats by ozone exposure. However, the increases in hyperthyroid rats were much greater, MIP-2 1.5-fold and MCP-1 11-fold, when compared to levels in controls following ozone. These changes appeared to be relatively specific; bronchoalveolar lavage fluid levels of interleukin (IL)-6, IL-4, and IL-10 were generally low or nondetectable across all of the studied groups at the 18-h postexposure time point. We also found that NF-kappaB binding activity was increased at both 4 and 18 h following ozone exposure in bronchoalveolar lavage cell extracts from hyperthyroid rats relative to the activity in control samples. Collectively, these results suggest that mechanisms contributing to the enhanced pulmonary inflammatory response to ozone in a hyperthyroid state include an increase in NF-kappaB activation and an upregulation of chemokine production.

Administration, Inhalation↗

PubMed2002

Particle in cell simulation of laser-accelerated proton beams for radiation therapy.

In this article we present the results of particle in cell (PIC) simulations of laser plasma interaction for proton acceleration for radiation therapy treatments. We show that under optimal interaction conditions protons can be accelerated up to relativistic energies of 300 MeV by a petawatt laser field. The proton acceleration is due to the dragging Coulomb force arising from charge separation induced by the ponderomotive pressure (light pressure) of high-intensity laser. The proton energy and phase space distribution functions obtained from the PIC simulations are used in the calculations of dose distributions using the GEANT Monte Carlo simulation code. Because of the broad energy and angular spectra of the protons, a compact particle selection and beam collimation system will be needed to generate small beams of polyenergetic protons for intensity modulated proton therapy.

Computer Simulation↗

PubMed2001

Neutral pion threshold production at Q(2) = 0.05 GeV(2)/c(2) and chiral perturbation theory.

New data are presented on the p(e,e'p)pi(0) reaction at threshold at a four-momentum transfer of Q(2) = 0.05 GeV(2)/c(2). The data were taken with the three-spectrometer setup of the A1 Collaboration at the Mainz Microtron MAMI. The complete center of mass solid angle was covered up to a center of mass energy of 4 MeV above threshold. Combined with measurements at three different values of the virtual photon polarization epsilon, the structure functions sigma(T), sigma(L), sigma(TT), and sigma(TL) are determined. The results are compared with calculations in heavy baryon chiral perturbation theory and with a phenomenological model. The measured cross section is significantly smaller than both predictions.

Journal Article↗

PubMed2001

Flexibility and nucleation in sickle hemoglobin.

We have studied the self-assembly of Hemoglobin C-Harlem (HbC-Harlem), a double mutant of hemoglobin that possesses the beta6 Glu-->Val mutation of sickle hemoglobin (HbS) plus beta73 Asp-->Asn. By electron microscopy we find it forms crystals, rather than the wrapped multistranded fibers seen in HbS. Fourier transforms of the crystals yield unit cell parameters indistinguishable from crystals of HbS. Differential interference contrast (DIC) microscopy and birefringence also show crystal formation rather than the polymers or domains seen for HbS, while the growth patterns showed radiating crystal structures rather than simple linear crystalline forms. The solubility of the assembly was measured using a photolytic micromethod over a temperature range of 17-31 degrees C in 0.15 M phosphate buffer and found to be essentially the same as that of fibers of HbS. The assembly kinetics were observed by photolysis of the carbon monoxide derivative, and the mass of assembled hemoglobin was found to grow exponentially, with onset times that were stochastically distributed for small volumes. The stochastic onset of assembly showed strong concentration dependence, similar to but slightly greater than that seen in sickle hemoglobin nucleation. These observations suggest that like HbS, HbC-Harlem assembly proceeds by a homogeneous nucleation process, followed by heterogeneous nucleation. However, relative to HbS, both homogeneous and heterogeneous nucleation are suppressed by almost 11 orders of magnitude. The slowness of nucleation can be reconciled with the similarity of the solubility to HbS by an increase in contact energy coupled with a decrease in vibrational entropy recovered on assembly. This also explains the linearity of the double-strands, and agrees with the chemical nature of the structural replacement.

Anemia, Sickle Cell↗

PubMed2001

Fluorescence immunoassay system based on the use of a pH-sensitive phase-separating polymer.

Poly(N-isopropylacrylamide-co-methacrylic acid) [P(NIPAAm-co-MAA)], a linear water-soluble pH-sensitive phase-separating polymer, was synthesized and used as a novel separation carrier for the reactants in immunoassay. This polymer precipitates out of water below a critical pH 5.8 at 37 degrees C and redissolves when the pH of solution is above 6.2. The characteristic of this polymer makes it possible to carry out the immunochemical steps of an immunoassay in a true solution and then to quickly separate the resulting product from the reaction mixture. The above approach was applied to determination of alpha-fetoprotein with the competitive immunoassay format. Compared with traditional ELISA using the same reactants, the proposed method was much faster (the assay time decreased from 100-120 to 30 min) and showed similar sensitivity, i.e., 0.04 ng/mL. In addition, a sandwich immunoassay method for the determination of hepatitis B surface antigen was also studied, and the results showed that the pH phase-separating immunoassay could be carried out through a sandwich or a competitive method. This general technique may also be used for a wide variety of separation processes in addition to immunoassay, in which a specific component is to be isolated for analysis, recovery, or disposal.

Acrylamides↗

PubMed2001

UV Induces phosphorylation of protein kinase B (Akt) at Ser-473 and Thr-308 in mouse epidermal Cl 41 cells through hydrogen peroxide.

The exposure of mammalian cells to UV irradiation leads to the activation of transcription factors and protein kinases, which are believed to be responsible for the carcinogenic effects of excessive sun exposure. The present study investigated the effect of UV exposure on reactive oxygen species (ROS) generation and protein kinase B (Akt) phosphorylation in epidermal cells and determined if a relationship exists between these UV responses. Exposure of mouse epidermal JB6 Cl 41 cells to UV radiation led to specific phosphorylation of Akt at Ser-473 and Thr-308 in a time-dependent manner. This phosphorylation was confirmed by the observation that overexpression of Akt mutant, Akt-T308/S473A, attenuated phosphorylation of Akt at Ser-473 and Thr-308. UV radiation also generated ROS as measured by electron spin resonance (ESR) in JB6 Cl 41 cells. The generation of ROS by UV radiation was measured further by H(2)O(2) and O(-.2) fluorescence staining assays. The mechanism of ROS generation involved reduction of molecular oxygen to O(-.2), which generated H(2)O(2) through dismutation. H(2)O(2) produced .OH via a metal-independent pathway. The scavenging of UV-generated H(2)O(2) by N-acety-l-cyteine (NAC, a general antioxidant) or catalase (a specific H(2)O(2) inhibitor) inhibited Akt phosphorylation at Ser-473 and Thr-308, whereas the pretreatment of cells with sodium formate (an .OH radical scavenger) or superoxide dismutase (an O(-.2) radical scavenger) did not show any inhibitory effects. Furthermore, treatment of cells with H(2)O(2) increased UV-induced phosphorylation of Akt at Ser-473 and Thr-308. These results demonstrate that UV radiation generates a whole spectrum of ROS including O(-.2), .OH, and H(2)O(2) and induces phosphorylation of Akt at Ser-473. Among the various ROS, H(2)O(2) seems most potent in mediating UV-induced phosphorylation of Akt at Ser-473 and Thr-308. It is possible that Akt may play a role in the carcinogenesis effects by UV radiation.

Animals↗

PubMed2001

Vanadium-induced nuclear factor of activated T cells activation through hydrogen peroxide.

The present study investigated the role of reactive oxygen species (ROS) in activation of nuclear factor of activated T cells (NFAT), a pivotal transcription factor responsible for regulation of cytokines, by vanadium in mouse embryo fibroblast PW cells or mouse epidermal Cl 41 cells. Exposure of cells to vanadium led to the transactivation of NFAT in a time- and dose-dependent manner. Scavenging of vanadium-induced H(2)O(2) with N-acety-L-cyteine (a general antioxidant) or catalase (a specific H(2)O(2) inhibitor) or the chelation of vanadate with deferoxamine, resulted in inhibition of NFAT activation. In contrast, an increase in H(2)O(2) generation by the addition of superoxide dismutase or NADPH enhanced vanadium-induced NFAT activation. This vanadate-mediated H(2)O(2) generation was verified by both electron spin resonance and fluorescence staining assay. These results demonstrate that H(2)O(2) plays an important role in vanadium-induced NFAT transactivation in two different cell types. Furthermore, pretreatment of cells with nifedipine, a calcium channel blocker, inhibited vanadium-induced NFAT activation, whereas and ionomycin, two calcium ionophores, had synergistic effects with vanadium for NFAT induction. Incubation of cells with cyclosporin A (CsA), a pharmacological inhibitor of the phosphatase calcineurin, blocked vanadium-induced NFAT activation. All data show that vanadium induces NFAT activation not only through a calcium-dependent and CsA-sensitive pathway but also involved H(2)O(2) generation, suggesting that H(2)O(2) may be involved in activation of calcium-calcineurin pathways for NFAT activation caused by vanadium exposure.

Animals↗

PubMed2001

Measurement of the recoil polarization in the p(e-->, e'p-->)pi(0) reaction at the Delta(1232) resonance.

The recoil proton polarization has been measured in the p(e-->,e'p-->)pi(0) reaction in parallel kinematics around W = 1232 MeV, Q2 = 0.121 (GeV/c)2, and epsilon = 0.718 using the polarized cw electron beam of the Mainz Microtron. All three proton polarization components, Px/P(e) = (-11.4+/-1.3+/-1.4)%, P(y) = (-43.1+/-1.3+/-2.2)%, and P(z)/P(e) = (56.2+/-1.5+/-2.6)%, could be measured simultaneously. The Coulomb quadrupole to magnetic dipole ratio, CMR = (-6.4+/-0.7(stat)+/-0.8(syst))%, was determined from Px in the framework of the Mainz Unitary Isobar Model. The consistency among the reduced polarizations and the extraction of the ratio of longitudinal-to-transverse response is discussed.

Journal Article↗

PubMed2001

[Frequent loss of heterozygosity on chromosome 4 in human hepatocellular carcinoma].

OBJECTIVE: Few previous studies have shown high frequency of loss of heterozygosity (LOH) on chromosome 4q in hepatocellular carcinoma (HCC). We define more clearly the deletion regions that may harbor the putative tumor suppressor genes in HCC. METHODS: Forty-eight cases of HCC and their corresponding non-tumor liver tissues were investigated with 12 microsatellite polymorphic markers for LOH. RESULTS: Twenty-one of 48 (44%) and 30 of 48 (63%) tumors showed LOH on at least one locus on the short and the long arms respectively. Two distinct common deleted regions (CDR) with different patterns of deletion were identified. The first CDR was located on 4q22-q25, between loci D4S392 and D4S1625. In addition, 17 of 27 (63%) of the informative tumors showed LOH on this region with locus D4S406 and constituted the highest rate of LOH on chromosome 4. The second CDR was located at 4q27-q31, between loci D4S1625 and D4S1652. CONCLUSION: There are at least two tumor suppressor loci on 4q.

Carcinoma, Hepatocellular↗

PubMed2001

Opposite effect of NF-kappa B and c-Jun N-terminal kinase on p53-independent GADD45 induction by arsenite.

Cell cycle checkpoint, a major genomic surveillance mechanism, is an important step in maintaining genomic stability and integrity in response to environmental stresses. Using cells derived from human bronchial epithelial cells, we demonstrate that NF-kappaB and c-Jun N-terminal kinase (JNK) reciprocally regulate arsenic trioxide (arsenite)-induced, p53-independent expression of GADD45 protein, a cell cycle checkpoint protein that arrests cells at the G(2)/M phase transition. Inhibition of NF-kappaB activation by stable expression of a kinase-mutated form of IkappaB kinase caused increased and prolonged induction of GADD45 by arsenite. In contrast, the induction of GADD45 by arsenite was transient and less potent in cells where the NF-kappaB activation pathway was normal. Analysis of the cell cycle profile by flow cytometry indicated that NF-kappaB inhibition potentiates arsenite-induced G(2)/M cell cycle arrest. Abrogation of JNK activation, on the other hand, decreased GADD45 expression induced by arsenite, suggesting a role for JNK activation in GADD45 induction. These results indicate a molecular mechanism by which NF-kappaB and JNK may differentially contribute to cell cycle regulation in response to arsenite.

Arsenites↗

PubMed2001

Urothelial function reconsidered: a role in urinary protein secretion.

Mammalian bladder epithelium functions as an effective permeability barrier. We demonstrate here that this epithelium can also function as a secretory tissue directly involved in modifying urinary protein composition. Our data indicate that normal bovine urothelium synthesizes, as its major differentiation products, two well-known proteases: tissue-type plasminogen activator and urokinase, as well as a serine protease inhibitor, PP5. Moreover, we demonstrate that the urothelium secretes these proteins in a polarized fashion into the urine via a cAMP- and calcium-regulated pathway. Urinary plasminogen activators of ruminants are therefore urothelium derived rather then kidney derived as in some other species; this heterogeneity may have evolved in response to different physiological or dietary factors. In conjunction with our recent finding that transgenic mouse urothelium can secrete ectopically expressed human growth hormone into the urine, our data establish that normal mammalian urothelium can function not only as a permeability barrier but also as a secretor of urinary proteins that can play physiological or pathological roles in the urinary tract.

3T3 Cells↗

PubMed2001

Event-related changes in neuromagnetic activity associated with syncopation and synchronization timing tasks.

For low rhythmic rates (1.0 to approximately 2.0 Hz), subjects are able to successfully coordinate finger flexion with an external metronome in either a syncopated (between the beats) or synchronized (on each beat) fashion. Beyond this rate, however, syncopation becomes unstable and subjects spontaneously switch to synchronization to maintain a 1:1 stimulus/response relationship. We used a whole-head magnetometer to investigate the spatiotemporal dynamics of neuromagnetic activity (MEG) associated with both coordinative patterns at eight different rates spanning the range 1.0-2.75 Hz. Timing changes in the event-related fields accompanied transitions from syncopation to synchronization and followed the placement of the motor response within each stimulus/response cycle. Decomposition of event-related fields into component auditory and motor brain responses revealed that the amplitude of the former decreased with increasing coordination rate whereas the motor contribution remained approximately constant across all rates. Such an interaction may contribute to changes in auditory-motor integration that cause syncopation to become unstable. Examination of event-related changes in high frequency bands revealed that MEG signal power in the beta band (15-30 Hz) was significantly lower during syncopated coordination in sensors covering the contralateral sensorimotor area suggesting a dependence of beta rhythm amplitude on task difficulty. Suppression of beta rhythms was also stronger during synchronization preceded by syncopation, e.g., after subjects had switched, when compared with a control condition in which subjects synchronized throughout the entire range of rates.

Acoustic Stimulation↗