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Biomedical subjects

H A Wright

Publications and source records attributed to H A Wright.

At least 19 recordsLinked to original sources
PubMed2001

LHX3 transcription factor mutations associated with combined pituitary hormone deficiency impair the activation of pituitary target genes.

The Lhx3 LIM homeodomain transcription factor is critical for pituitary gland formation and specification of the anterior pituitary hormone-secreting cell types. Two mutations in LHX3, a missense mutation changing a tyrosine to a cysteine and an intragenic deletion that results in a truncated protein lacking the DNA-binding homeodomain, have been identified in humans. These mutations were identified in patients with retarded growth and combined pituitary hormone deficiency and also abnormal neck and cervical spine development. For both the LHX3a and LHX3b isoforms, we compared the ability of wild type and mutant LHX3 proteins to trans-activate pituitary genes, bind DNA recognition elements, and interact with partner proteins. The tyrosine missense mutation inhibits the ability of LHX3 to induce transcription from selected target genes but does not prevent DNA binding and interaction with partner proteins such as NLI and Pit-1. Mutant LHX3 proteins lacking a homeodomain do not bind DNA and do not induce transcription from pituitary genes. These studies demonstrate that mutations in the LHX3 isoforms impair their gene regulatory functions and support the hypothesis that defects in the LHX3 gene cause complex pituitary disease in humans.

Animals↗
PubMed1994

Radiotoxicity of platinum-195m-labeled trans-platinum (II) in mammalian cells.

The chemotoxicity and radiotoxicity of trans-dichlorodiammineplatinum (II) labeled with 195mPt (trans-195mPt) are investigated to ascertain the potential of radioplatinum coordination complexes as antineoplastic agents. Platinum-195m, with a half-life of about 4 days, is a prolific emitter of low-energy Auger electrons because of the high probability of internal conversion in its isomeric transitions. The kinetics of cellular uptake and retention after incubation and the radiotoxicity of this Auger electron emitter in the form of trans-195mPt is investigated using cells of the Chinese hamster V79 cell line. The cellular uptake of 195mPt reaches a plateau in about 3 to 5 h of incubation and varies nonlinearly with the extracellular concentration of radioactivity. The radioactivity is eliminated from the cells after incubation with an effective half-life of 24 h. Cell survival data, when corrected for the chemical toxicity of nonradiolabeled trans-platinum, give a cell survival curve typical for radiations with high linear energy transfer. At 37% survival, the mean lethal cellular uptake is about 1.0 mBq/cell. Dosimetric considerations, based on subcellular distribution of the radionuclide, yield a value of 4.8 for the relative biological effectiveness when compared with 250 kVp X rays. Theoretical Monte Carlo track-structure calculations indicate that the density of radical species produced in liquid water in the immediate vicinity of a 195mPt decay site is substantially greater than the density of species along the track of a 5.3 MeV alpha particle. This explains qualitatively the efficacy of 195mPt in causing high-LET radiation type biological effects. The extreme radiotoxicity of intranuclearly localized 195mPt, in conjunction with the proclivity of platinum chemotherapy agents to bind to DNA in the cell nucleus, suggests that the combination of chemical effects and the effects of Auger electrons that can be obtained with radioplatinum coordination complexes may have potential in the treatment of cancer.

Animals↗
PubMed1991

Radiation damage to a biomolecule: new physical model successfully traces molecular events.

For the first time, a complete computer simulation of physical and chemical reactions at the molecular level has been used to calculate the yield of a chemical species resulting from irradiation of a biological molecule in aqueous solution. Specifically, when a solution of glycylglycine is irradiated anaerobically, an ammonia molecule is released by the action of a hydrated electron, which is produced by irradiation of water. In the computations, Monte Carlo techniques are used to simulate the statistical progression of molecular events as they are assumed to occur. These include the initial physical ionization and excitation of water molecules along a particle track in the liquid; the subsequent formation of free radicals and other species: and the random diffusion and chemical reactions of the species with each other, the solvent, and solute molecules. We have calculated and measured the yield of ammonia from irradiation of glycylglycine with 250 kVp x-rays as a function of glycylglycine concentration between 0.01 and 1.2 M. Excellent agreement is obtained between predicted and measured results. The literal simulation of events, combined with specific experimental measurements, offers a powerful new tool for studying mechanisms of radiation action and damage at the molecular level.

Ammonia↗
PubMed1991

Spatial distributions of inelastic events produced by electrons in gaseous and liquid water.

The spatial distributions of ionizations and other inelastic events in charged-particle tracks are important quantities that influence the final outcome of radiation interaction. Calculations of such distributions are presented for the tracks of electrons in the energy range 100 eV to 10 keV in liquid water and water vapor, and the results are compared. The distributions include the frequency of nearest-neighbor distances for all inelastic events, the mean nearest-neighbor distances for ionizations and for all inelastic events as a function of electron energy, the frequency of distances between all ionizations and all inelastic events, and the farthest distances between all inelastic events in electron tracks. The physical differences between liquid water and water vapor are discussed in terms of the respective inverse mean free paths, the collision spectra, and the nonlocalization of energy losses that are likely to occur in the liquid.

Electrons↗
PubMed1990

Monte Carlo calculations of free ammonia production in deoxygenated solutions of glycylglycine irradiated by X rays and 60Co gamma rays.

Detailed-history Monte Carlo computer codes were used to simulate the formation, diffusion, and chemical reaction of free-radical species within deoxygenated aqueous solutions of glycylglycine irradiated by 250-kVp X rays and by 60Co gamma rays. In one reaction, hydrated electrons react with the glycylglycine solute to produce unbound, or free, ammonia. This reaction is complete by 10(-6) s within individual electron tracks for glycylglycine concentrations greater than or equal to 0.025 M. For solute concentrations from 0.025 to 1.2 M, calculated G values of free ammonia are in excellent agreement with measured values. In addition, the computer model predicts a statistically significant difference between the G value of free ammonia produced under X irradiation and that produced under 60Co gamma irradiation.

Ammonia↗
PubMed1987

A method of obtaining neutron dose and dose equivalent from digital measurements and analysis of recoil-particle tracks.

The feasibility of a digital approach to neutron dosimetry has been investigated. Such an approach uses an ionization detector capable of measuring the numbers of electrons produced within various subvolumes of a chamber gas along a charged-particle track. In addition, a computer algorithm is used to infer absorbed dose, LET, and dose equivalent given this digital track-structure information for each event. This paper describes one detector design capable of providing digital track-structure information and discusses examples of proton and C-ion tracks calculated from a Monte Carlo charged-particle transport code. The associated computer algorithm is presented next with its verification accomplished by running a variety of recoil particles through a simulated detector volume and comparing the resulting average energy deposition and dose equivalent to those unfolded by the algorithm.

Neutrons↗
PubMed1985

A Monte Carlo primer for health physicists.

The basic ideas and principles of Monte Carlo calculations are presented in the form of a "primer" for health physicists. A simple integral with a known answer is evaluated by two different Monte Carlo approaches. Random numbers, which underlie Monte Carlo work, are discussed, and a sample table of random numbers generated by a hand calculator is presented. Monte Carlo calculations of dose and linear energy transfer (LET) from 100-keV neutrons incident on a tissue slab are discussed. The random-number table is used in a hand calculation of the initial sequence of events for a 100-keV neutron entering the slab. Some pitfalls in Monte Carlo work are described. While this primer addresses mainly the "bare bones" of Monte Carlo, a final section briefly describes some of the more sophisticated techniques used in practice to reduce variance and computing time.

Health Physics↗
PubMed1985

Calculation of heavy-ion tracks in liquid water.

Detailed Monte Carlo calculations are presented of proton and alpha-particle tracks in liquid water. The computations treat the interactions of the primary particle and all secondary electrons on a statistical, event-by-event basis to simulate the initial physical changes that accompany the passage of an ion through water. Our methods for obtaining the cross sections needed for such calculations are described. Inelastic scattering probabilities (inverse mean free paths) are derived from a complex dielectric response function constructed for liquid water, based on experimental and theoretical data. Examples of partial cross sections for ionization and excitation by protons are shown. The computation of electron transport and energy loss includes exchange, elastic scattering, and a scheme for the delocalization of energy shared collectively by a large number of electrons in the condensed medium. Several examples of calculated proton and alpha-particle tracks are presented and discussed. The meaning and significance of the concept of a track core are briefly addressed in the light of this work. The present paper treats only the initial, physical changes produced by radiation in water (in approximately 10(-15) s in local regions of a track). The work described here is used in calculations that we have reported in other publications on the later chemical development of charged-particle tracks.

Alpha Particles↗
PubMed1982

Monte Carlo calculations of initial energies of electrons in water irradiated by photons with energies up to 1GeV.

Previous calculations of the initial energies of electrons produced in water irradiated by photons are extended to 1 GeV by including pair and triplet production. Calculations were performed with the Monte Carlo computer code PHOEL-3, which replaces the earlier code, PHOEL-2. Tables of initial electron energies are presented for single interactions of monoenergetic photons at a number of energies from 10 keV to 1 GeV. These tables can be used to compute kerma in water irradiated by photons with arbitrary energy spectra to 1 GeV. In addition, separate tables of Compton-and pair-electron spectra are given over this energy range. The code PHOEL-3 is available from the Radiation Shielding Information Center, Oak Ridge National Laboratory, Oak Ridge, TN 37830.

Computers↗
PubMed1979

Influence of beam characteristics and detector size in negative-pion dose studies.

Dose calculations were performed for a tissue phantom irradiated by uniform circular beams of negative pions with an assumed gaussian momentum distribution. The mean momentum of the pions was varied from 104.4 to 171.5 MeV/c (mean range 5-20 cm in unit-density tissue) and the momentum spread from 0 to 5% of the mean. Depth-dose curves are shown for different mean momenta and momentum spreads. The radial distribution of dose as a function of distance from the beam axis was computed at different depths for a beam with a mean momentum of 153.4 MeV/c and spread of 2%. The responses of detectors of different sizes used to measure centre-line dose for this beam were shown by calculating depth-dose curves for detectors of radii 0.5, 1.0, 1.5, 2.0, 3.0 and 4.0 cm. Calculations were also performed for beams having radii of 1, 2 and 3 cm. Depending on particular conditions, it appears that considerable care may often be needed to infer the absorbed dose at a given location in a phantom irradiated by a negative-pion beam.

Elementary Particles↗
PubMed1978

Calculated yields and slowing-down spectra for electrons in liquid water: implications for electron and photon RBE.

Detailed Monte Carlo calculations have been carried out of slowing-down spectra and yields for a number of end-points for electrons in liquid water. These investigations were made to study differences in physical effects of different low-LET radiations and implications for RBE. Initial electron energies from 1 keV to 1 MeV were used, and all secondary electrons were followed in the computations unitl their energies fell below 10 eV. Though there are substantial differences in the slowing-down spectra at energies near and above the K-shell ionisation potential of oxygen, the energy spectrum of electrons at lower energies is found to be essentially independent of the initial energy of the primary electron. The number of events per unit energy deposited is also essentially independent of the primary electron energy. Based on these calculations, there appears to be little basis for ascribing differences in RBE for low-LET radiations to differences in physical effects produced by secondary electrons of low energy (less than or equal to 1 keV).

Electrons↗