Charles E. Swenberg

Terrestrial space radiation and its biological effects

Radiation Environment in Space.- The Earths Trapped and Transient Space Radiation Environment.- Ambient Electron Density Distribution at About 500 km Altitude at the Earths Ionosphere.- The Space Radiation Environment at 840 km.- Solar Proton Event Forecasts.- Radiation Hazards in Low Earth Orbit, Polar Orbit, Geosynchronous Orbit, and Deep Space.- Analysis of the Radiative Risk During Hermes Mission.- Biological Effects of Space Radiation.- Heavy Ion Effects.- Heavy Ion Effects on Cells: An Approach to Theoretical Understanding.- Cosmic Ray HZE Particle Effects in Biological Systems: Results of Experiments in Space.- Effects of Low and High LET Radiation on Neoplastic Transformation in Cells and the Importance of Single Track Effects in Space.- Effects of LET, Fluence and Particle Energy on Inactivation, Chromosomal Aberrations and DNA Strand Breaks.- Induction of Chromosome Aberrations in Chinese Hamster Cells After Heavy Ion Irradiation.- Heavy Ion Radiation Effects on Single Spores of Bacillus Subtilis.- Biological Action of Heavy Ion Irradiation on Individual Yeast Cells.- Delta-Electron Emission in Heavy Ion Collisions.- Genetic Effects.- The Role of Repair Processes in Cellular and Genetical Response to Radiation.- Reactions of Genetic Systems to Heavy Ions: Acute and Late Effects.- Nature of Radiation Induced Mutations. Experimental Approaches on the Question of Intragenic Events.- Genetic and Developmental Responses of Radiation Sensitive Mutants of the Nematode, C. elegans, to Ultraviolet, High and Low LET Radiation.- Ionizing Radiation Induced Mutagenesis: Molecular Genetic Changes and Role of DNA Lesions and Repair.- Cellular Effects.- Radiation Physics Related to Biology.- Biochemistry of Subcellular and Cellular Radiation Effects.- High Energy Proton Induced Mutations in Cultured Chinese Hamster Cells.- Cultures of Erythroleukemic Cells (K-562) on a Stratospheric Balloon Flight.- Transposition of Retrotransposons After Gamma and UV Irradiation.- Flow Cytometry Techniques for the Study of Irradiated Hematopoietic Stem Cells.- The Kinetics of UV-Induced Thymine Dimerization.- Effects of Ultrahigh Vacuum and UV Irradiation on Transforming DNA of Haemophilus Influenzae.- Effect of High-Vacuum, Deep Temperatures and VUV Irradiation on Bacterial Spores.- Physiology Radiobiology.- Selected Examples of Degenerative Late Effects Caused by Particulate Radiations in Normal Tissues.- Delayed Effects of Proton Irradiation in the Lens and Integument: A Primate Model.- Life Shortening and Causes of Death in Experimental Animals Following Whole-Body Exposure to Ionizing Radiation.- Acute Radiation Syndromes in Man.- Extrapolation of Animal Data to Man.- Radiation Induced Damage to the Regenerative Capacity of Surgically Traumatized Rat Femur After Single Doses of X-Rays.- Cardiopulmonary Effects Following Local Irradiation of the Heart in Adult Male Wistar/Neuherberg Rats.- Post-Irradiation Alterations in Cerebral Blood Flow.- Analysis of the Involvement of the Terrestrial Space Radiation in the Microgravity Effects on DrosophilaMelanogaster Development and Aging.- Behavioral and Neurobiological Aspects.- Current Trends in Behavioral Radiobiology.- Effects of Iron Particles on Behavior and Brain Function: Initial Studies.- Correlative Motor Behavioral and Striatal Dopaminergic Alterations Induced by 56Fe Radiation.- Protection From Space Radiation.- Variation of Galactic Cosmic Radiation by Solar Modulation, Geomagnetic Shielding and Shielding by Material.- Radiation Problems in Manned Spaceflight - European Efforts.- Space Radiation Exposures for Manned Polar Missions: A Parametric Study.- Protection of Polar Platforms from Penetrating Radiation.- Galactic Cosmic Radiation Doses to Astronauts Outside the Magnetosphere.- DNA and Radioprotection.- Excision Repair is Enhanced by WR-2721 Radioprotection.- Impact of Spaceflight Environment on Radiation Response.- Radiation Protection Guidelines for Space Missions.- Dosimetry.- Space Radiation Dosimetry on U.S. and Soviet Manned Missions.- Measurements of Cosmic Ray LET-Spectra for the D1 Mission Using Plastic Nuclear Track Detectors.- Cosmic Ray LET-Spectrum Measured in the Spacelab 2 Mission.- New Directions in Space Dosimetry.- Summary.- Participants.

Enhancement of topoisomerase I-mediated unwinding of supercoiled DNA by the radioprotector WR-33278

The radioprotector WR-33278, the disulfide of WR-1065 (N-(2-mercaptoethyl)-1,3-diaminopropane), is shown to stimulate eukaryotic topoisomerase I unwinding of negatively supercoiled DNA. This observation suggests the possibility that some protection may be conferred to DNA either by a decrease in its supercoiled state or by altering directly other enzymatic processes. This is the first report of a radioprotective compound stimulating an enzyme involved in DNA structure and synthesis.

Cytoskeletal involvement in neuronal learning: a review

This paper introduces the ideas of neural networks in the context of currently recognized cellular structures within neurons. Neural network models and paradigms require adaptation of synapses for learning to occur in the network. Some models of learning paradigms require information to move from axon to dendrite. This motivated us to examine the possibility of intracellular signaling to mediate such signals. The cytoskeleton forms a substrate for intracellular signaling via material transport and other putative mechanisms. Furthermore, many experimental results suggest a link between the cytoskeleton and cognitive processing. In this paper we review research on intracellular signaling in the context of neural network learning.

Synthesis and Characterization of Stereoisomers of 5,6-Dihydro-5,6-Dihydroxythymidine

Abstract Six products were isolated by reverse phase HPLC from the reaction of thymidine with osmium tetroxide. Four of the products were identified as stereoisomers of 5,6-dihydro-5.6-dihydroxythymidine (TG). The absolute configurations of these four compounds (from the shortest to the longest HPLC retention times) were determined by two-dimensional nuclear magnetic resonance spectroscopy to be (-)-trans-5S.6S-, (+)-trans-5R,6R-, (-)-cis-5R,6S-, and (+)-cis-5S,6R-5,6-dihydro-5,6-dihydroxythymidine. The other two products were dimers with unknown linking sites. Parameters of the mass and nuclear magnetic resonance spectra are reported and discussed.

Neutron-induced Free Radicals in Oriented DNA

Samples of oriented DNA containing 30 per cent water were irradiated with neutrons at 77 K. The electron spin resonance (e.s.r.) spectra obtained from these irradiated DNA samples show that the formation of radicals is different when the incident neutrons are parallel or perpendicular to the DNA helix. When the incident neutrons are perpendicular to the DNA helix the e.s.r. spectra of thymine and guanine ionic radicals (T-., G+.) are observed. An additional e.s.r. spectrum corresponding to the hydrogen addition radical on thymine (TH.) is observed when the incident neutrons are parallel to DNA helix. The TH. radical appears to be formed by protonation of T-. .

Alterations in Phosphate Metabolism during Cellular Recovery of Radiation Damage in Yeast

We have examined alterations in phosphate pools during cellular recovery from radiation damage in intact, wild-type diploid yeast cells using 31P nuclear magnetic resonance (NMR) spectroscopy. Concurrent cell survival analysis was determined following exposure to 60Co gamma-radiation. Cells held in citrate-buffered saline (CBS) showed increased survival with increasing time after irradiation (liquid holding recovery, LHR) with no further recovery beyond 48 h. Addition of 100 mmol dm-3 glucose to the recovery medium resulted in greater recovery. In the presence of 5 mmol dm-3 2-deoxyglucose (2-DG), LHR was completely inhibited. NMR analyses were done on cells perfused in agarose threads and maintained under conditions similar to those in the survival studies. ATP was observable by NMR only when glucose was present in the recovery medium. In control cells, ATP concentrations increased and plateaued with increasing recovery time. With increasing radiation dose the increase in ATP was of lesser magnitude, and after 2000 Gy no increase was observed. These observations suggest that either the production of ATP in irradiated cells is suppressed or there is enhanced ATP utilization for repair of radiation damage. In CBS with 100 mmol dm-3 glucose, a dose-dependent decrease in polyphosphate (polyP) was detectable with no concurrent increase in inorganic phosphate (Pi). In the absence of an external energy source, such as glucose, there was a slight increase in Pi. This suggests that polyP may be used as an alternative energy supply. When 2-DG was present in the recovery medium, polyP decreased, but there was a simultaneous increase in Pi with increasing radiation dose and recovery time. This suggests that the polyP are hydrolyzed as a source of phosphates for repair of radiation damage.

Intracellular mechanisms in neuronal learning: adaptive models

The cytoskeletal intraneuronal structure and some candidate mechanisms for signaling within nerve cells are described. Models were developing for the interaction of the cytoskeleton with cell membranes, synapses, and an internal signaling model that renders back-error propagation biologically plausible. Orientation-selective units observed in the primate motor cortex may be organized by such internal signaling mechanisms. The impact on sensorimotor systems and learning is discussed. It is concluded that the cytoskeletons anatomical presence suggested that it plays a potentially key role in neuronal learning. The cytoskeleton could participate in synaptic processes by supporting the synapse and possibly by sending intracellular signals as well. Paradigms for adaptational mechanisms and information processing can be modeled utilizing the cytoskeleton and cytoskeletal signals.<<ETX>>

Chemical, Molecular Biology, and Genetic Techniques for Correlating DNA Base Damage Induced by Ionizing Radiation with Biological End Points

The types of DNA base damage induced by ionizing radiation, and also relevant model system investigations on replication and mutagenesis, are reviewed in this paper. Recent advances in DNA synthesis technology and site-directed mutagenesis suggest that these methods can be profitably utilized to correlate specific types of DNA base damage with selected biological end points. A deeper insight can be obtained into the molecular origins of mutations, and the effects of base sequence surrounding the lesions on the nature and types of mutations.

DNA and Radioprotection

Ionizing radiation generates a number of different types of free radicals throughout a cell that can result in a nonselective alteration to various cell target macromolecules. The interaction between target molecules and free radicals and the generation of molecular ions is thought to lead to both the immediate or acute effects and the long-term, or chronic effects of ionizing radiation. Radioprotection refers to some appropriate countermeasure which helps suppress the effects of ionizing radiation. It is appropriate to define a true chemical protector as a substance which when administered to animals or added to culture medium shortly before exposure to ionizing radiation significantly decreases the harmful effects of radiation whereas if given after irradiation, produces no alteration in measurable endpoints. Chemicals administered after radiation are generally classified as therapeutic agents and exert their effects either by enhancing the endogenous cellular recovery processes of damaged cells or in the replacement of dead cells. In fact, there are substances which are known to be effective against the deleterious effects of ionizing radiation whether given either before or after irradiation; an example is olive oil (Maqsood and Ashikawa, 1960) or parathyroid hormone (Rixon, Whitfield and Yondale, 1958). Some substances, such as superoxide dismutase (SOD), protect against radiation induced cell transformation when administered either before or after irradiation.

Estimation of open dwell time and problems of identifiability in channel experiments

Abstract Membrane channels can open or close in response to a change in membrane voltage. An important neurophysiological problem is the estimation of the duration of a channel opening, called the open dwell time. In many experiments, however, the recorded measurement is often a summation of several open dwell times from multi-channels. Under a standard kinetic model, this would give rise to a distribution of the total open dwell time which is a mixture of gamma distributions with binomial weights. For such a mixture, the maximum likelihood estimates are difficult to compute. We illustrate an easily implementable estimation method introduced by Le Cam. The method produces asymptotically optimal estimates. We also discuss problems of parameter identification and the potential bias associated with using a continuous-time model to analyze discrete-time data.