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Biomedical subjects

D P Chen

Publications and source records attributed to D P Chen.

17 recordsLinked to original sources

Anomalous electronic Raman scattering in NaxCoO2.yH2O.

Raman scattering experiments on NaxCoO2.yH2O single crystals show a broad electronic continuum with a pronounced peak around 100 cm(-1) and a cutoff at approximately 560 cm(-1) over a wide range of doping levels. The electronic Raman spectra in superconducting and nonsuperconducting samples are similar at room temperature, but evolve in markedly different ways with decreasing temperature. For superconducting samples, the low-energy spectral weight is depleted upon cooling below T* approximately 150 K, indicating the opening of a pseudogap that is not present in nonsuperconducting materials. Weak additional phonon modes observed below T* suggest that the pseudogap is associated with charge ordering.

Journal Article↗

Nonmagnetic insulator state in Na1CoO2 and phase separation of na vacancies.

Crystallographic, magnetic, and NMR properties of a Na1CoO2 single crystal with x approximately = 1 are presented. We identify the stoichiometric Na1CoO2 phase, which is shown to be a nonmagnetic insulator, as expected for homogeneous planes of Co3+ ions with S = 0. In addition, we present evidence that, because of slight average Na deficiency, chemical and electronic phase separation leads to a segregation of Na vacancies into the well-defined, magnetic, Na0.8CoO2 phase. The importance of phase separation is discussed in the context of magnetic order for x approximately = 0.8 and the occurrence of a metal-insulator transition for x --> 1.

Journal Article↗

Magnetic ordering and spin waves in Na0.82CoO2.

NaxCoO2, the parent compound of the recently synthesized superconductor Na(x)CoO(2):yH(2)O, exhibits bulk antiferromagnetic order below approximately 20 K for 0.75</=x</=0.9. We have performed neutron scattering experiments in which we observed Bragg reflections corresponding to A-type antiferromagnetic order in a Na0.82CoO2 single crystal and characterized the corresponding spin-wave dispersions. The spin waves exhibit a strongly energy-dependent linewidth. The in-plane and out-of-plane exchange constants resulting from a fit to a nearest-neighbor Heisenberg model are similar in magnitude, which is unexpected in view of the layered crystal structure of NaxCoO2. Possible implications of these observations are discussed.

Journal Article↗

Charge ordering and magnetopolarons in Na0.82CoO2.

Using spectral ellipsometry, we measured the dielectric function of a Na(0.82(2))CoO2 crystal that exhibits bulk antiferromagnetism with T(N)=19.8 K. We identify two prominent transitions as a function of temperature. The first one at 280 K involves marked changes of the electronic and lattice responses that are indicative of charge ordering in the CoO2 layers. The second transition occurs around T(N)=19.8 K and reveals sizable spin-charge coupling. The data are discussed in terms of charge ordering and formation of magnetopolarons due to a charge-induced spin-state transition of adjacent Co3+ ions.

Journal Article↗

Two-dimensional geometry of spin excitations in the high-transition-temperature superconductor YBa2Cu3O6+x.

The fundamental building block of the copper oxide superconductors is a Cu4O4 square plaquette. The plaquettes in most of these materials are slightly distorted to form a rectangular lattice, for which an influential theory predicts that high-transition-temperature (high-T(c)) superconductivity is nucleated in 'stripes' aligned along one of the axes. This theory received strong support from experiments that indicated a one-dimensional character for the magnetic excitations in the high-T(c) material YBa2Cu3O6.6 (ref. 4). Here we report neutron scattering data on 'untwinned' YBa2Cu3O6+x crystals, in which the orientation of the rectangular lattice is maintained throughout the entire volume. Contrary to the earlier claim, we demonstrate that the geometry of the magnetic fluctuations is two-dimensional. Rigid stripe arrays therefore appear to be ruled out over a wide range of doping levels in YBa2Cu3O6+x, but the data may be consistent with liquid-crystalline stripe order. The debate about stripes has therefore been reopened.

Journal Article↗

Mechanism of action of Tripterygium Wilfordii polyglycoside on experimental endometriosis.

PURPOSE OF INVESTIGATION: This study was designed to examine the therapeutic effectiveness and mechanism of action of Tripterygium Wilfordii polyglycoside (TWP) in the treatment of endometriosis. METHODS: An experimental endometriosis model was developed using New Zealand White rabbits where endometrial tissue was autotransplanted into the peritoneum. Six weeks after transplantation, a total of 22 rabbits were randomly placed into two groups: Group I (n=17) was treated with TWP (10 mg/kg/day) and Group 2 (n=5) served as the water-fed control for three successive months. The volume of endometrial implants was measured before and after administration of TWP and water. Immune and endocrine systems were investigated in the normal phase, six weeks after induction of endometriosis, and three months after TWP treatment and water administration. RESULTS: After treatment with TWP, the average volume of endometrial implants significantly decreased (p < 0.0001), and the antiendometrial antibody (EmAb) level decreased (p < 0.05) to near normal levels, but it did not decrease in the untreated controls. Serum FSH and LH levels also decreased after TWP treatment. Furthermore, electron microscopic examination of the pituitary ultrastructure revealed morphological changes in gonadotropic cells (G-cell) after treatment with TWP, and changes gradually disappeared four weeks after withdrawal of TWP. CONCLUSION: This study indicates that TWP has both hormonal and immune system action that is effective as a medical treatment for experimental endometriosis by modulating both reproductive endocrine functions and immunosuppression that results in remission of the disease.

Animals↗

Phenotype II triploid pregnancy and study of the parental origin of the extra set of chromosomes with fluorescence microsatellite analysis: case report.

Triploidy can reflect diandry (dispermy or diploid sperm) or digyny(diploid ovum). The former is likely to result in the type I phenotype with a partial mole with an appropriate-for-gestational age fetus rarely surviving beyond 20 weeks and a large, cystic placenta. The latter, however, is characterized by a type II phenotype with severe intrauterine growth retardation (IUGR) with longer in utero survival and a small, non-molar placenta. We report on a 22-year-old woman, gravida 2, para1, in the 31st week of gestation who was referred to our prenatal clinic for evaluation of severe IUGR and oligohydramnios. Late cytogenetic karyotyping from cordocentesis revealed a triploidy of 69, XXX. In the 33rd week of gestation, the mother went through spontaneous labor delivering an IUGR 1180 gm fetus and a small, non-molar placenta. The fetus died immediately and was sent for autopsy. In addition to cleft lip and palate, the infant had pulmonary lobation abnormalities. Fluorescence microsatellite analysis of fetal and parental samples confirmed that the extra set of chromosomes present in the proband was a result of a maternal meiosis I nondisjunction error. This may help study of genomic imprinting on human development.

Adult↗

Non-radioactive Southern hybridization for early diagnosis of alpha-thalassemia with southeast Asian-type deletion in Taiwan.

Alpha-thalassemia has been estimated to account for over 60% of hydrops fetalis cases in Taiwan. The most common genotypic lesion found in alpha-thalassemia-1 cases in Taiwan is deletion of a large segment of the alpha-globin gene cluster, termed the Southeast Asian-type deletion (-SEA/; further referred to as SEA-type deletion). Seven chorionic villus samples (CVS) from pregnancies of couples both heterozygous for SEA-type deletion were studied. Non-radioactive Southern-blot hybridization using the dig-alkaline phosphatase detection system was developed to fulfill this purpose. The results were compared with corresponding polymerase chain reaction (PCR) data to elucidate the effectiveness of these two protocols in the diagnosis of the SEA-type deletion. The data showed that of the seven CVS, three demonstrated a distinctive band pattern, indicating their homozygous status of SEA-type deletion, whereas two showed heterozygous patterns, and the other two were free of the deletion. Homozygosity of the deletion was confirmed by Southern-blot hybridization performed on DNA samples extracted from the abortus tissue. However, two of the three cases with SEA-type deletion showed heterozygous PCR results. Maternal cell contamination could be responsible for the artifacts in the PCR results, but the influence due to the contamination is minimal in non-radioactive Southern-blot hybridization. We concluded that PCR is suitable for screening of carrier adults with SEA-type deletion, and non-radioactive Southern hybridization is ideal for early prenatal diagnosis of the SEA-type deletion.

Asia, Southeastern↗

Selectivity and permeation in calcium release channel of cardiac muscle: alkali metal ions.

Current was measured from single open channels of the calcium release channel (CRC) of cardiac sarcoplasmic reticulum (over the range +/-180 mV) in pure and mixed solutions (e.g., biionic conditions) of the alkali metal ions Li+, K+, Na+, Rb+, Cs+, ranging in concentration from 25 mM to 2 M. The current-voltage (I-V) relations were analyzed by an extension of the Poisson-Nernst-Planck (PNP) formulation of electrodiffusion, which includes local chemical interaction described by an offset in chemical potential, which likely reflects the difference in dehydration/solvation/rehydration energies in the entry/exit steps of permeation. The theory fits all of the data with few adjustable parameters: the diffusion coefficient of each ion species, the average effective charge distribution on the wall of the pore, and an offset in chemical potential for lithium and sodium ions. In particular, the theory explains the discrepancy between "selectivities" defined by conductance sequence and "selectivities" determined by the permeability ratios (i.e., reversal potentials) in biionic conditions. The extended PNP formulation seems to offer a successful combined treatment of selectivity and permeation. Conductance selectivity in this channel arises mostly from friction: different species of ions have different diffusion coefficients in the channel. Permeability selectivity of an ion is determined by its electrochemical potential gradient and local chemical interaction with the channel. Neither selectivity (in CRC) seems to involve different electrostatic interaction of different ions with the channel protein, even though the ions have widely varying diameters.

Animals↗

Change in centromeric and acentromeric micronucleus frequencies in human populations after chronic radiation exposure.

Acute radiation exposure of humans was observed to induce various forms of cytogenetic damage, including increased frequencies of micronuclei and chromosomal aberrations. However, the cytogenetic effects of chronic low dose radiation exposure in vivo needs further characterization. Sixteen subjects with chronic low dose rates of gamma-radiation exposure from 60Co-contaminated steel in radioactive buildings were compared with seven non-exposed reference subjects for micronucleus frequencies after they relocated. By in situ hybridization using a digoxigenin-labeled anti-alpha all human centromere probe, the exposed subjects were shown to have a significant increase in cytochalasin B-modulated micronucleus (CBMN) frequencies, as well as a significant increase in centromere-positive (C+) CBMN, centromere-negative (C-) CBMN, total C+signals, single C+ MN signals and multiple C+ signals/1000 binucleated cells (BN). However, decreases in the ratios C+MN/C- MN and C+MN/total CBMN (%) were also noted in the exposed subjects. By mixed effects analysis, considering individuals from the same families, the C- MN and single C+ MN/1000 BN were both positively and moderately associated with previous cumulative exposure. When the time period of relocation post-exposure (relocation time or RT) was considered, total C+MN and multiple C+MN/1000 BN were negatively and significantly associated with RT. Moreover, the C+MN, C- MN, C+MN/C- MN ratio and single C+MN/1000 BN were all negatively and moderately associated with RT, but not with exposure dose. This suggested that acentromeric and single or multiple centromeric CBMN cytogenetic damage seems to disappear differentially in human subjects post chronic low dose radiation exposure.

Adolescent↗

Anomalous mole fraction effect, electrostatics, and binding in ionic channels.

Ionic channels bathed in mixed solutions of two permeant electrolytes often conduct less current than channels bathed in pure solutions of either. For many years, this anomalous mole fraction effect (AMFE) has been thought to occur only in single-file pores containing two or more ions at a time. Most thinking about channels incorporates this view. We show here that the AMFE arises naturally, as an electrostatic consequence of localized ion specific binding, if the average current through a channel is described by a theory (Poisson-Nernst-Planck, PNP) that computes the average electric field from the average concentration of charges in and near the channel. The theory contains only those ion-ion interactions mediated by the mean field, and it does not enforce single filing. The AMFE is predicted by PNP over a wide range of mean concentrations of ions in the channel; for example, it is predicted when (on the average) less, or much less, than one ion is found in the channel's pore. In this treatment, the AMFE arises, in large measure, from a depletion layer produced near a region of ion-specific binding. The small excess concentration of ions in the binding region repels all nearby ions of like charge, thereby creating a depletion layer. The overall conductance of the channel arises in effect from resistors in series, one from the binding region, one from the depletion zone, and one from the unbinding region. The highest value resistor (which occurs in the depletion zone) limits the overall series conductance. Here the AMFE is not the result of single filing or multiple occupancy, and so previous views of permeation need to be revised: the presence of an AMFE does not imply that ions permeate single file through a multiply occupied pore.

Binding Sites↗

Hydrodynamic model of temperature change in open ionic channels.

Most theories of open ionic channels ignore heat generated by current flow, but that heat is known to be significant when analogous currents flow in semiconductors, so a generalization of the Poisson-Nernst-Planck theory of channels, called the hydrodynamic model, is needed. The hydrodynamic theory is a combination of the Poisson and Euler field equations of electrostatics and fluid dynamics, conservation laws that describe diffusive and convective flow of mass, heat, and charge (i.e., current), and their coupling. That is to say, it is a kinetic theory of solute and solvent flow, allowing heat and current flow as well, taking into account density changes, temperature changes, and electrical potential gradients. We integrate the equations with an essentially nonoscillatory shock-capturing numerical scheme previously shown to be stable and accurate. Our calculations show that 1) a significant amount of electrical energy is exchanged with the permeating ions; 2) the local temperature of the ions rises some tens of degrees, and this temperature rise significantly alters for ionic flux in a channel 25 A long, such as gramicidin-A; and 3) a critical parameter, called the saturation velocity, determines whether ionic motion is overdamped (Poisson-Nernst-Planck theory), is an intermediate regime (called the adiabatic approximation in semiconductor theory), or is altogether unrestricted (requiring the full hydrodynamic model). It seems that significant temperature changes are likely to accompany current flow in the open ionic channel.

Electrochemistry↗

Sodium in gramicidin: an example of a permion.

The reaction path and free energy profile of Na+ were computed in the interior of the channel protein gramicidin, with the program MOIL. Gramicidin was represented in atomic detail, but surrounding water and lipid molecules were not included. Thus, only short range interactions were investigated. The permeation path of the ion was an irregular spiral, far from a straight line. Permeation cannot be described by motions of a single Na+ ion. The minimal energy path includes significant motion of water and channel atoms as well as motion of the permeating ion. We think of permeation as motion of a permion, a quasi-particle that includes the many body character of the permeation process, comparable with quasi-particles like holes, phonons, and electrons of solid-state physics. Na+ is accompanied by a plug of water molecules, and motions of water, Na+, and the atoms of gramicidin are highly correlated. The permion moves like a linear polymer made of waters and ion linked and moving coherently along a zigzag line, following the reptation mechanism of polymer transport. The effective mass, free energy, and memory kernel (of the integral describing time-dependent friction) of short range interactions were calculated. The effective mass of the permion (properly normalized) is much less than Na+. Friction varies substantially along the path. The free energy profile has two deep minima and several maxima. In certain regions, the dominant motions along the reaction path are those of the channel protein, not the permeating ion: there, ion waits while the other atoms move. At these waiting sites, the permion's motion along the reaction path is a displacement of the atoms of gramicidin that prepare the way for the Na+ ion.

Biophysical Phenomena↗

Fura 2 determination of [Ca2+]i in isolated perfused heart using R wave-gated electromechanical shutters.

We describe a novel and relatively inexpensive spectrofluorescence system that supplies rapidly alternating wavelengths to either a standard cuvette or an isolated perfused heart. Its use is illustrated by determining changes in cytosolic intracellular Ca2+ concentration ([Ca2+]i) by using the Ca(2+)-sensitive fluorescent dye fura 2 in a rabbit heart preparation. The system uses two precision electromechanical shutters (capable of gating with respect to the electrocardiographic R wave for signal averaging) allowing alternate fura 2 excitation wavelengths (340 and 380 nm) without moving optical components and uses a fiber optic for conducting excitation and collecting epifluorescence. Sample recordings tracing the [Ca2+]i transient in an entire cardiac cycle and in capturing specific isolated regions (diastole and systole) of the cycle are presented. Limitations of this low-cost but easily implemented system are discussed.

Animals↗

Flux, coupling, and selectivity in ionic channels of one conformation.

Ions crossing biological membranes are described as a concentration of charge flowing through a selective open channel of one conformation and analyzed by a combination of Poisson and Nernst-Planck equations and boundary conditions, called the PNP theory for short. The ion fluxes in this theory interact much as ion fluxes interact in biological channels and mediated transporters, provided the theoretical channel contains permanent charge and has selectivity created by (electro-chemical) resistance at its ends. Interaction occurs because the flux of different ionic species depends on the same electric field. That electric field is a variable, changing with experimental conditions because the screening (i.e., shielding) of the permanent charge within the channel changes with experimental conditions. For example, the screening of charge and the shape of the electric field depend on the concentration of all ionic species on both sides of the channel. As experimental interventions vary the screening, the electric field varies, and thus the flux of each ionic species varies conjointly, and is, in that sense, coupled. Interdependence and interaction are the rule, independence is the exception, in this channel.

Biological Transport, Active↗

Constant fields and constant gradients in open ionic channels.

Ions enter cells through pores in proteins that are holes in dielectrics. The energy of interaction between ion and charge induced on the dielectric is many kT, and so the dielectric properties of channel and pore are important. We describe ionic movement by (three-dimensional) Nemst-Planck equations (including flux and net charge). Potential is described by Poisson's equation in the pore and Laplace's equation in the channel wall, allowing induced but not permanent charge. Asymptotic expansions are constructed exploiting the long narrow shape of the pore and the relatively high dielectric constant of the pore's contents. The resulting one-dimensional equations can be integrated numerically; they can be analyzed when channels are short or long (compared with the Debye length). Traditional constant field equations are derived if the induced charge is small, e.g., if the channel is short or if the total concentration gradient is zero. A constant gradient of concentration is derived if the channel is long. Plots directly comparable to experiments are given of current vs voltage, reversal potential vs. concentration, and slope conductance vs. concentration. This dielectric theory can easily be tested: its parameters can be determined by traditional constant field measurements. The dielectric theory then predicts current-voltage relations quite different from constant field, usually more linear, when gradients of total concentration are imposed. Numerical analysis shows that the interaction of ion and channel can be described by a mean potential if, but only if, the induced charge is negligible, that is to say, the electric field is spatially constant.

Biophysical Phenomena↗