Biomedical subjects

Paul Todd

Publications and source records attributed to Paul Todd.

13 recordsLinked to original sources

PubMed2005

Diet as a factor in behavioral radiation protection following exposure to heavy particles.

Major risks associated with radiation exposures on deep space missions include carcinogenesis due to heavy-particle exposure of cancer-prone tissues and performance decrements due to neurological damage produced by heavy particles. Because exposure to heavy particles can cause oxidative stress, it is possible that antioxidants can be used to mitigate these risks (and possibly some health risks of microgravity). To assess the capacity of antioxidant diets to mitigate the effects of exposure to heavy particles, rats were maintained on antioxidant diets containing 2% blueberry or strawberry extract or a control diet for 8 weeks prior to exposure to 1.5 or 2.0 Gy of accelerated iron particles at Brookhaven National Laboratory. Following irradiation rats were tested on a series of behavioral tasks: amphetamine-induced taste aversion learning, operant responding and spatial learning and memory. The results indicated that the performance of the irradiated rats maintained on the antioxidant diets was, in general, significantly better than that of the control animals, although the effectiveness of the diets ameliorating the radiation-induced deterioration in performance varied as a function of both the specific diet and the specific endpoint. In addition, animals fed antioxidant diets prior to exposure showed reduced heavy particle-induced tumorigenesis one year after exposure compared to the animals fed the control diet. These results suggest that antioxidant diets have the potential to serve as part of a system designed to provide protection to astronauts against the effects of heavy particles on exploratory missions outside the magnetic field of the earth.

Aging↗

PubMed2004

Experiments with osteoblasts cultured under hypergravity conditions.

To understand further the role of gravity in osteoblast attachment, osteoblasts were subjected to hypergravity conditions in vitro. Scanning electron microscopy of all confluent coverslips from FPA units show that the number of attached osteoblasts was similar among gravitational levels and growth durations (~90 cells/microscopic field). Specifically, confluent 1.0 G control cultures contained an average of 91 +/- 8 cells/field, 3.3 G samples had 88 +/- 8 cells/field, and 4.0 G cultures averaged 90 +/- 7 cells/field. The sparsely plated cultures assessed by immunohistochemistry also had similar numbers of cells at each time point (l.0 G was similar to 3.3 and 4.0 G), but cell number changed from one time point to the next as those cells proliferated. Immunohistochemistry of centrifuged samples showed an increase in number (up to 160% increase) and thickness (up to 49% increase) of actin fibers, a decrease in intensity of fibronectin fluorescence (18-23% decrease) and an increase in number of vinculin bulbs (202-374% increase in number of vinculin bulbs/area). While hypergravity exposure did not alter the number of attached osteoblasts, it did result in altered actin, fibronectin, and vinculin elements, changing some aspects of osteoblast- substrate adhesion.

Actins↗

PubMed2004

Overview of the spaceflight radiation environment and its impact on cell biology experiments.

Variables studied in typical cellular radiation biology experiments are cell killing, mutagenesis, transformation to malignancy, heritable damage, and DNA damage and repair. Dose response curves for cells exposed to low-LET radiations and some high LET radiations are well known. The low-LET dose rate in low earth orbit is roughly 1.0 mSv/day, the heavy-ion (Z>2) flux is about 1.0 particle/cm2-s corresponding to about 0.3 mSv/day, and the integrated neutron flux is roughly 2 neutrons/cm2-s corresponding to 0.012 mGy/d or, assuming a QF of 10, 0.12 mSv/d. Published dose-response curves were used to estimate the probability that a mammalian cell will be affected by each of the above types of damage. As a general approximation the exposure of an experimental cell population to the space radiation environment for 100 days will result in the following probabilities of damage per cell: cell killing based on clonogenicity 0.02, mutagenesis per locus based on phenotype analysis 1 x 10(-6), point mutation induction 2 x 10(-8) per locus, malignant transformation in vitro based on colony morphology 1.2 x 10(-5), heritable damage based on colony size 0.02, and induced DNA double-strand breaks based on fragment analysis by electrophoresis 3.5/cell or 0.26/cell after repair. Most of these figures are accurate to within a factor of 2. Thus the spaceflight radiation environment has essentially undetectable impact on typical cell biology experiments unless experimental goals involve the precise measurement of one of the above end-points. Other in vitro end-points, such as tissue morphogenesis and cell differentiation, are expected to be similarly unaffected by the spaceflight radiation environment.

Animals↗

PubMed2004

Overview of SHOT hardware capabilities and range of cell biology experiment designs.

Cell science hardware is currently available for lease or production by SHOT(R). The SHOT Avian Development Facility (ADF) is a single middeck locker experiment containing two carousels capable of rotating at variable g. Each carousel accommodates 18 40-ml vessels that can be adapted for the cultivation of avian or reptilian eggs, small invertebrates, zebra fish, small plants, seeds, spores, cells or tissues. Cellcult Cassettes contain a small (20-50 ml) rotating cylindrical culture vessel with feed media reservoir, pumps, waste bag and sample collection bags. Cultures can be rotated, perfused, fed, aerated and sampled automatically or on remote command. Fluid Processing Cassettes contain a flexible combination of feed, culture and fixative bags with valves and pumps programmable for various feeding and fixing protocols. Dynacult Cassettes contain a cylindrical bioreactor with differentially rotating walls, pumps and valves for feeding and sampling, and pH and oxygen measurement. All cassettes are doubly contained and are accommodated by a computerized, thermally controlled processing facility, the Advanced Space Experiment Processor, which processes three cassettes, or the Biotechnology Thermal Environment Carrier, which holds up to six cassettes.

Animals↗

PubMed2003

Space radiation health: a brief primer.

The goals of space radiation health research are to understand qualitatively and quantitatively the ionizing radiations present in the space environment, identify qualitatively and quantitatively the risks associated with these radiations, and discover countermeasures to mitigate these risks. The articles that follow address each of these three components of space radiation health research. This article introduces the basic science and definitions underlying radiation health research and protection. Space radiations consist of energetic protons from the sun, protons and electrons from the sun that are trapped in the Earth's magnetic field, and cosmic rays that include energetic nuclei of H, He, C, N, O and Fe atoms. The risks presented to space travelers by these radiations include cancer due to protons and cosmic-ray exposure, immune failure due to high-dose solar proton storms, and possible neurological effects caused by single tracks of cosmic-ray heavy nuclei. Potential countermeasures include shielding, medication consisting of radical scavengers, anti-oxidant consumption, cytokines, and cell transplants.

Cosmic Radiation↗

PubMed2003

Biological countermeasures in space radiation health.

Exposure to the types of ionizing radiation encountered during space travel may cause a number of health-related problems, but the primary concern is related to the increased risk of cancer induction in astronauts. The major types of radiation considered to be of importance during space travel are protons and particles of high atomic number and high energy (HZE particles). It is now clear that biological countermeasures can be used to prevent or reduce the levels of biological consequences resulting from exposure to protons or HZE particles, including the induction of cancer, immunosuppression and neurological defects caused by these types of ionizing radiation. Research related to the dietary additions of agents to minimize the risks of developing health-related problems which can result from exposure to space radiations is reviewed.

Animals↗

PubMed2002

The high-speed Hydra-Plus-One system for automated high-throughput protein crystallography.

An automated high-throughput dispenser has been developed for the setup of protein crystallization trials by vapor diffusion or Microbatch methods. The Hydra-Plus-One is composed of a Hydra-PP system equipped with a motorized XYZ-platform, 96 precision glass syringes and a single-channel microsolenoid dispenser, which transfers 100 nl-50 micro l of protein solution with an accuracy of > 90% at a speed of 60s per 96 wells. Up to 300 micro l of premixed cocktails can be aspirated with the 96-syringe-assembly and dispensed into reservoir and droplet wells within 60s. The Hydra-Plus-One combines high precision, reliability and speed in a cost-effective high-throughput system ideally suited for protein crystallization

Bacterial Proteins↗

PubMed2002

Multistage electrophoresis II: treatment of a kinetic separation as a pseudoequilibrium process.

An electrophoresis device is described which separates cells, particles, proteins and other separands by collecting samples having decreasing electrophoretic mobility in a train of inverted cavities while an electric field is applied between the inverted cavities and a sample cuvette containing a mixture of cells, particles, proteins or other separands. A circular plate is provided for the inverted cavities, and this circular plate is rotated to collect fractions. The system utilizes an innovative purification method that combines free electrophoresis and multistage extraction in an instrument capable of separating living cells, particles, and proteins in useful quantities at high concentrations. Most multistage processes are based on equilibrium separations, but electrophoresis is a kinetic separation; therefore, a pseudoequilibrium paradigm was developed for use in optimizing separation parameters including number of stages and electrophoresis time per stage. This paradigm allows the application of McCabe-Thiele type analysis, and it was calculated, for example, that two separands differing by 20% in electrophoretic mobility can be purified to 95% purity with acceptable yield in about seven stages. Laboratory experiments demonstrated a 95% purification in four stages of a separand originally present at 4% when electrophoretic mobilities differed by 80%.

Anions↗

PubMed2002

Sliding-cavity fluid contactors in low-gravity fluids, materials, and biotechnology research.

The well-known method of sliding-cavity fluid contactors used by Gosting for diffusion measurements and by Tiselius in electrophoresis has found considerable use in low-gravity research. To date, sliding-cavity contactors have been used in liquid diffusion experiments, interfacial transport experiments, biomolecular crystal growth, biphasic extraction, multistage extraction, microencapsulation, seed germination, invertebrate development, and thin-film casting. Sliding-cavity technology has several advantages for spaceflight: it is simple, it accommodates small samples, samples can be fully enclosed, phases can be combined, multiple samples can be processed at high sample density, real-time observations can be made, and mixed and diffused samples can be compared. An analysis of the transport phenomena that govern the sliding-cavity method is offered. During sliding of one liquid over another flow rates between 0.001 and 0.1m/sec are developed, giving Reynolds numbers in the range 0.1-100. Assuming no slip at liquid-solid boundaries shear rates are of the order 1sec(-1). The measured consequence is the transfer of 2-5% of the content of a cavity to the opposite cavity. In the absence of gravity, buoyancy-driven transport is assumed absent. Transport processes are limited to (1) molecular diffusion, in which reactants diffuse toward one another at rates that depend on their diffusion coefficient and concentration gradient (Fick's second law), (2) solutocapillary (Marangoni) flow driven by surface-tension gradients, (3) capillary flow (drop spreading) at liquid-solid three-phase lines leading to immiscible phase demixing, and (4) vapor-phase diffusive mass transfer in evaporative processes. Quantitative treatment of these phenomena has been accomplished over the past few years in low-gravity research in space and on aircraft.

Biotechnology↗

PubMed2002

Heritable non-lethal damage to cultured human cells irradiated with heavy ions.

UNLABELLED: During interplanetary flights the nuclei of all of a crew member's cells could be traversed by at least one high-LET (Linear Energy Transfer) cosmic-ray particle. In mammalian cells irradiated in vitro about 1 in 10,000 of the surviving cells traversed by heavy particles is transformed to malignancy or mutated. What, if anything, happens to the remaining >99% of surviving cells? A retrospective analysis of archived data and samples from heavy-ion irradiation experiments with cultured human cells in vitro indicated that heavy ions caused a dose- and LET-dependent reduction in growth rates of progeny of irradiated cells, based on colony-size distributions. The maximum action cross section for this effect is between 100 and 300 microm2, at least as large as the cell nuclear area and up to 3 times the cross section for cell killing. Thus, heritable slow growth is the most prevalent effect of high-LET radiations on cultured animal cells, which may have implications for crew health during deep space travel. DISCLAIMER: The views expressed in this article are those of the author(s) and do not necessarily reflect the views or policies of the USEPA.

Cells↗

PubMed2001

Modeling Disjoining Pressures in Submicrometer Liquid-Filled Cylindrical Geometries.

This work develops models for calculating the disjoining pressures of a cylindrical fluid "plug", specifically in submicrometer cylindrical pores. This modeling produces closed-form, cylindrical-pore disjoining pressures for London/van der Waals and solute/pore-wall adsorption interactions, which are the slit-pore models with the characteristic pore size replaced by the radius and multiplied by 6, resulting in a 48-fold or more increase in magnitude. In addition, this work contains a numerical solution for electrostatic interactions. The result of the numerical solution was a 9-fold increase in the modeled disjoining pressure compared to that in the slit-pore model. The cylindrical models may apply to the chemical coating of the interior walls of cylindrical pores or to the thermodynamics within droplets after the breakup of a fluid coating a surface. However, the application used as the base case in this paper is the extension of transport and thermodynamic laws for porous media, previously developed with capillary pressure models, to fully saturated porous media with submicrometer-sized pores. As such, the models could apply to mass transport in ultrafiltration, nanofiltration, and reverse-osmosis membranes. Copyright 2001 Academic Press.

Journal Article↗

PubMed1997

Investigation of space flight effects on Escherichia coli and a proposed model of underlying physical mechanisms.

Previous investigations have reported that space flight may produce a stimulating effect on microbial metabolism; however, the specific underlying mechanisms associated with the observed changes have not yet been identified. In an effort to systematically evaluate the effect of space flight on each phase of microbial growth (lag, exponential and stationary), a series of experiments was carried out using in vitro suspension cultures of Escherichia coli aboard seven US Space Shuttle missions. The results indicated that, as a result of space flight, the lag phase was shortened, the duration of exponential growth was increased, and the final cell population density was approximately doubled. A model was derived from these cumulative data in an attempt t associate gravity-dependent, extracellular transport phenomena with unique changes observed in each specific phase of growth. It is suggested that a cumulative effect of gravity may have a significant impact on suspended cells via their fluid environment, where an immediate, direct influence of gravity might otherwise be deemed negligible.

Bacteriological Techniques↗

PubMedDate not supplied

Osteoblasts subjected to spaceflight and simulated space shuttle launch conditions.

To understand further the effects of spaceflight on osteoblast-enriched cultures, normal chicken calvarial osteoblasts were flown aboard shuttle flight STS-77, and the total number of attached cells was determined. Spaceflight and control cultures were chemically fixed 3 h and 3 d after launch. These fixed cultures were processed for scanning electron microscopy (SEM). The SEM analysis showed that with just 3 d of exposure to spaceflight, coverslip cultures contained 300 +/- 100 cells/mm2, whereas 1G control samples contained a confluent monolayer of cells (2400 +/- 200 cells/mm2). Although the cultures flown in space experienced a drastic decline in cell number in just 3 d, without further experimentation it was impossible to determine whether the decline was a result of microgravity, the harsh launch environment, or some combination of these factors. Therefore, this research attempted to address the effect of launch by subjecting osteoblasts to conditions simulating shuttle launch accelerations, noise, and vibrations. No differences, compared with controls, were seen in the number of total or viable cells after exposure to these various launch conditions. Taken together, these data indicate that the magnitude of gravitational loading (3G maximum) and vibration (7.83G rms maximum) resulting from launch does not adversely affect osteoblasts in terms of total or viable cell number immediately, but launch conditions, or the microgravity environment itself, may start a cascade of events that over several d contributes to cell loss.

Animals↗