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Biomedical subjects

J W Wilson

Publications and source records attributed to J W Wilson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Estimation of neutron and other radiation exposure components in low earth orbit.

The interaction of high-energy space radiation with spacecraft materials generates a host of secondary particles, some, such as neutrons, are more biologically damaging and penetrating than the original primary particles. Before committing astronauts to long term exposure in such high radiation environments, a quantitative understanding of the exposure and estimates of the associated risks are required. Energetic neutrons are traditionally difficult to measure due to their neutral charge. Measurement methods have been limited by mass and weight requirements in space to nuclear emulsion, activation foils, a limited number of Bonner spheres, and TEPCs. Such measurements have had limited success in quantifying the neutron component relative to the charged components. We will show that a combination of computational models and experimental measurements can be used as a quantitative tool to evaluate the radiation environment within the Shuttle, including neutrons. Comparisons with space measurements are made with special emphasis on neutron sensitive and insensitive devices.

Astronauts↗
PubMed2001

Space radiation cancer risks and uncertainties for Mars missions.

Projecting cancer risks from exposure to space radiation is highly uncertain because of the absence of data for humans and because of the limited radiobiology data available for estimating late effects from the high-energy and charge (HZE) ions present in the galactic cosmic rays (GCR). Cancer risk projections involve many biological and physical factors, each of which has a differential range of uncertainty due to the lack of data and knowledge. We discuss an uncertainty assessment within the linear-additivity model using the approach of Monte Carlo sampling from subjective error distributions that represent the lack of knowledge in each factor to quantify the overall uncertainty in risk projections. Calculations are performed using the space radiation environment and transport codes for several Mars mission scenarios. This approach leads to estimates of the uncertainties in cancer risk projections of 400-600% for a Mars mission. The uncertainties in the quality factors are dominant. Using safety standards developed for low-Earth orbit, long-term space missions (>90 days) outside the Earth's magnetic field are currently unacceptable if the confidence levels in risk projections are considered. Because GCR exposures involve multiple particle or delta-ray tracks per cellular array, our results suggest that the shape of the dose response at low dose rates may be an additional uncertainty for estimating space radiation risks.

Cosmic Radiation↗
PubMed2001

Effects of three levels of alpha-tocopheryl acetate supplementation to feedlot cattle on performance of beef cuts during retail display.

Retail packages (n = 288; 24 of each product in each treatment group) of inside round steaks, T-bone steaks (strip loin and tenderloin), top sirloin steaks, and ground beef were used to evaluate effects of dietary supplementation of vitamin E to cattle on product performance during retail display. Products from control animals and cattle fed 500 IU x animal(-1) x d(-1) or 1,000 IU x animal(-1) x d(-1) were evaluated. Except for ground beef, dietary supplementation of vitamin E increased (P < 0.05) alpha-tocopherol concentrations in beef muscle from cattle fed 1,000 IU x animal(-1) x d(-1). Although not all differences were statistically significant, retail display-life was greater for all steaks from cattle fed 1,000 IU x animal(-1) x d(-1) than for those from control cattle. Ten percent of the inside round and tenderloin steaks from cattle fed 1,000 IU x animal(-1) x d(-1) had mean overall appearance scores of 3 ("moderately undesirable") at 72 to 78 h and 54 to 60 h, respectively, whereas 10% of the inside round and tenderloin steaks from control cattle had mean overall appearance scores of 3 at 54 to 60 h and 42 to 48 h, respectively. Each of the retail cuts in this study (irrespective of the amount of alpha-tocopheryl acetate that was fed to the animal that generated it) was categorized as "high," "medium," or "low," based on the alpha-tocopherol concentration in the primal cut or ground beef batch from which it originated. Retail cuts in the medium a-tocopherol concentration category had increased retail display life of 4.0 h for ground beef (P < 0.05) over those in the low alpha-tocopherol category. Retail cuts in the high alpha-tocopherol concentration category had increased retail display life of 10.7 h for inside round steaks and 4.0 h for ground beef (P < 0.05) over those in the medium concentration category. Vitamin E supplementation of cattle at 1,000 IU x animal(-1) x d(-1) for at least 100 d can be used to increase retail caselife and to improve the overall color acceptability of steaks and ground beef products. Although far from a perfect relationship, these data strongly suggest that increasing the alpha-tocopherol concentration in a beef cut will increase its retail case life.

Animal Feed↗
PubMed2001

Cidofovir treatment of progressive multifocal leukoencephalopathy in a patient receiving highly active antiretroviral therapy.

Progressive multifocal leukoencephalopathy (PML), a frequently fatal demyelinating disease caused by JC virus, occurs as an opportunistic infection in patients with acquired immunodeficiency syndrome. Curative therapy has been elusive, but recent reports suggest its improvement after institution of highly active antiretroviral therapy (HAART). We describe a case of PML that developed 6 months after the patient, a 55-year-old man, began to receive HAART. The PML progressed despite good virologic and immunologic response to HAART. Substantial symptomatic and radiographic improvement occurred after the addition of cidofovir to the treatment regimen. We reviewed the scientific literature on this rare occurrence of PML after institution of HAART and describe the patient characteristics, potential pathogenesis, and therapeutic options, including the successful use of cidofovir as an adjunctive agent.

AIDS-Related Opportunistic Infections↗
PubMed2001

Visual assessment of the radiation distribution in the ISS Lab module: visualization in the human body.

The US Lab module of the International Space Station (ISS) is a primary working area where the crewmembers are expected to spend majority of their time. Because of the directionality of radiation fields caused by the Earth shadow, trapped radiation pitch angle distribution, and inherent variations in the ISS shielding, a model is needed to account for these local variations in the radiation distribution. We present the calculated radiation dose (rem/yr) values for over 3,000 different points in the working area of the Lab module and estimated radiation dose values for over 25,000 different points in the human body for a given ambient radiation environment. These estimated radiation dose values are presented in a three dimensional animated interactive visualization format. Such interactive animated visualization of the radiation distribution can be generated in near real-time to track changes in the radiation environment during the orbit precession of the ISS.

Computer Simulation↗
PubMed2001

Shielded Heavy-Ion Environment Linear Detector (SHIELD): an experiment for the Radiation and Technology Demonstration (RTD) Mission.

Radiological assessment of the many cosmic ion species of widely distributed energies requires the use of theoretical transport models to accurately describe diverse physical processes related to nuclear reactions in spacecraft structures, planetary atmospheres and surfaces, and tissues. Heavy-ion transport models that were designed to characterize shielded radiation fields have been validated through comparison with data from thick-target irradiation experiments at particle accelerators. With the RTD Mission comes a unique opportunity to validate existing radiation transport models and guide the development of tools for shield design. For the first time, transport properties will be measured in free-space to characterize the shielding effectiveness of materials that are likely to be aboard interplanetary space missions. Target materials composed of aluminum, advanced composite spacecraft structure and other shielding materials, helium (a propellant) and tissue equivalent matrices will be evaluated. Large solid state detectors will provide kinetic energy and charge identification for incident heavy-ions and for secondary ions created in the target material. Transport calculations using the HZETRN model suggest that 8 g cm -2 thick targets would be adequate to evaluate the shielding effectiveness during solar minimum activity conditions for a period of 30 days or more.

Computer Simulation↗
PubMed2001

Optimized shielding for space radiation protection.

Future deep space mission and International Space Station exposures will be dominated by the high-charge and -energy (HZE) ions of the Galactic Cosmic Rays (GCR). A few mammalian systems have been extensively tested over a broad range of ion types and energies. For example, C3H10T1/2 cells, V79 cells, and Harderian gland tumors have been described by various track-structure dependent response models. The attenuation of GCR induced biological effects depends strongly on the biological endpoint, response model used, and material composition. Optimization of space shielding is then driven by the nature of the response model and the transmission characteristics of the given material.

Aluminum↗
PubMed2001

Radiation protection using Martian surface materials in human exploration of Mars.

To develop materials for shielding astronauts from the hazards of GCR, natural Martian surface materials are considered for their potential as radiation shielding for manned Mars missions. The modified radiation fluences behind various kinds of Martian rocks and regolith are determined by solving the Boltzmann equation using NASA Langley's HZETRN code along with the 1977 Solar Minimum galactic cosmic ray environmental model. To develop structural shielding composite materials for Martian surface habitats, theoretical predictions of the shielding properties of Martian regolith/polyimide composites has been computed to assess their shielding effectiveness. Adding high-performance polymer binders to Martian regolith to enhance structural properties also enhances the shielding properties of these composites because of the added hydrogenous constituents. Heavy ion beam testing of regolith simulant/polyimide composites is planned to validate this prediction. Characterization and proton beam tests are performed to measure structural properties and to compare the shielding effects on microelectronic devices, respectively.

Cosmic Radiation↗
PubMed2001

Creation and utilization of a World Wide Web based space radiation effects code: SIREST.

In order for humans and electronics to fully and safely operate in the space environment, codes like HZETRN (High Charge and Energy Transport) must be included in any designer's toolbox for design evaluation with respect to radiation damage. Currently, spacecraft designers do not have easy access to accurate radiation codes like HZETRN to evaluate their design for radiation effects on humans and electronics. Today, the World Wide Web is sophisticated enough to support the entire HZETRN code and all of the associated pre and post processing tools. This package is called SIREST (Space Ionizing Radiation Effects and Shielding Tools). There are many advantages to SIREST. The most important advantage is the instant update capability of the web. Another major advantage is the modularity that the web imposes on the code. Right now, the major disadvantage of SIREST will be its modularity inside the designer's system. This mostly comes from the fact that a consistent interface between the designer and the computer system to evaluate the design is incomplete. This, however, is to be solved in the Intelligent Synthesis Environment (ISE) program currently being funded by NASA.

Algorithms↗
PubMed2001

Neutron environments on the Martian surface.

Radiation is a primary concern in the planning of a manned mission to Mars. Recent studies using NASA Langley Research Center's HZETRN space radiation transport code show that the low energy neutron fluence on the Martian surface is larger than previously expected. The upper atmosphere of Mars is exposed to a background radiation field made up of a large number of protons during a solar particle event and mixture of light and heavy ions caused by galactic cosmic rays at other times. In either case, these charged ions interact with the carbon and oxygen atoms of the Martian atmosphere through ionization and nuclear collisions producing secondary ions and neutrons which then interact with the atmospheric atoms in a similar manner. In the past, only these downward moving particles have been counted in evaluating the neutron energy spectrum on the surface. Recent enhancements in the HZETRN code allow for the additional evaluation of those neutrons created within the Martian regolith through the same types of nuclear reactions, which rise to the surface. New calculations using this improved HZETRN code show that these upward moving neutrons contribute significantly to the overall neutron spectrum for energies less than 10 MeV.

Computer Simulation↗
PubMed2000

The effect of exogenous prostaglandin administration on tumor size and yield in Min/+ mice.

This study set out to examine the effect of exogenous prostaglandin (PG) administration on tumor development in Min/+ mice. Mice were treated with the stable prostaglandin E2 analogue 16,16-dimethyl-PGE2 from 6-18 weeks of age. Mice were sacrificed, and tumor burden was assessed using morphometric techniques. Parameters measured were median tumor size, mean tumor size, the proportion of the area of the gastrointestinal mucosa covered with tumor, and the number of tumors per 1000 mm2 of gastrointestinal mucosa. In addition, proliferative and apoptotic indices were determined. These measurements were carried out for all regions of the small intestine (i.e., duodenum, jejunum, upper ileum, and lower ileum) and the large intestine (i.e., cecum and mid-colon/rectum). 16,16-Dimethyl-PGE2-treated animals showed a significant decrease in tumor burden (by approximately 50-70%), in comparison with those animals that were treated with vehicle alone (0.001% ethanol in 0.9% sterile saline), in all regions of the intestine (at P = 0.008 or better). This effect was contributed to by a reduction in the number of tumors (by approximately 20-50%) and a reduction in tumor size (by approximately 10-70%). An increase in tumor cell turnover was associated with this decrease in tumor burden, as determined by the changes in the levels of thymidine incorporation (significant at P = 0.003), apoptosis, and mitosis (nonsignificant).

16,16-Dimethylprostaglandin E2↗
PubMed2000

Natural transfer of viable microbes in space.

The possibility and probability of natural transfer of viable microbes from Mars to Earth and Earth to Mars traveling in meteoroids during the first 0.5 Ga and the following 4 Ga are investigated, including: --radiation protection against the galactic cosmic ray nuclei and the solar rays, dose rates as a function of the meteorite's radial column mass (radius x density), combined with dose rates generated by natural radioactivity within the meteorite; and survival curves for some bacterial species using NASA's HZETRN transport code --other factors affecting microbe survival: vacuum; central meteorite temperatures at launch, orbiting, and arrival; pressure and acceleration at launch; spontaneous DNA decay; metal ion migration --mean sizes and numbers of unshocked meteorites ejected and percentage falling on Earth, using current semiempirical results --viable flight times for the microbe species Bacillus subtilis and Deinococcus radiodurans R1 --the approximate fraction of microbes (with properties like the two species studied) viably arriving on Earth out of those ejected from Mars during the period 4 Ga BP to the present time, and during the 700 Ma from 4.5 to 3.8 Ga. Similarly, from Earth to Mars. The conclusion is that if microbes existed or exist on Mars, viable transfer to Earth is not only possible but also highly probable, due to microbes' impressive resistance to the dangers of space transfer and to the dense traffic of billions of martian meteorites which have fallen on Earth since the dawn of our planetary system. Earth-to-Mars transfer is also possible but at a much lower frequency.

Bacillus subtilis↗
PubMed2000

Cosmic ray hits in the central nervous system at solar maximum.

It has been suggested that a manned mission to Mars be launched at solar maximum rather than at solar minimum to minimize the radiation exposure to galactic cosmic rays. It is true that the number of hits from highly ionizing particles to critical regions in the brain will be less at solar maximum, and it is of interest to estimate how much less. We present here calculations for several sites within the brain from iron ions (z = 26) and from particles with charge, z, greater than or equal to 15. The same shielding configurations and sites in the brain used in an earlier paper for solar minimum are employed so that direct comparison of results between the two solar activity conditions can be made. A simple pressure-vessel wall and an equipment room onboard a spacecraft are chosen as shielding examples. In the equipment room, typical results for the thalamus are that the probability of any particles with 7 greater than or equal to 15 and from 2.3 percent to 1.3 percent for iron ions. The extra shielding provided in the equipment room makes little difference in these numbers. We conclude that this decrease in hit frequency (less than a factor of two) does not provide a compelling reason to avoid solar minimum for a manned mission to Mars. This conclusion could be revised, however, if a very small number of hits is found to cause critical malfunction within the brain.

Aerospace Medicine↗
PubMed2000

Persistent airway T-lymphocyte activation in chronic corticosteroid-treated symptomatic asthma.

BACKGROUND: A small proportion of patients with asthma have persistent symptoms despite regular treatment with high-dose inhaled and/or oral corticosteroids. There is little information regarding immunopathology in such patients. OBJECTIVE: To compare airway inflammatory changes in subjects with chronic corticosteroid-dependent symptomatic asthma (n = 5) and subjects with asthma that was clinically well controlled on inhaled corticosteroid therapy (n = 9). Subjects in the corticosteroid-dependent group were receiving long-term treatment with oral prednisolone and high-dose inhaled corticosteroids. METHODS: Subjects underwent fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy. T-lymphocytes subsets and activation markers in BAL fluid and peripheral blood were determined by FACS analysis. Bronchial biopsies were stained immunohistochemically, and numbers of inflammatory cells quantitated. Inflammatory mediators in BAL fluid were measured by immunoassay. RESULTS: There was significantly greater expression of CD25 (P = .02) and HLA-DR (P = .04) by BAL fluid T-lymphocytes in corticosteroid-treated symptomatic asthmatics. In bronchial biopsies there were no significant differences between the two groups in the numbers of AA1+ cells (mast cells), EG2+ cells (eosinophils) or MT1+ T-lymphocytes. Levels of albumin, histamine, tryptase, and eosinophil cationic protein in BAL fluid did not differ significantly between groups. CONCLUSIONS: Chronic corticosteroid-treated symptomatic asthma is associated with persistent airway T-lymphocyte activation. This, however, is not necessarily accompanied by the recruitment and activation of inflammatory cells within the airways.

Administration, Inhalation↗
PubMed2000

Analysis of MIR-18 results for physical and biological dosimetry: radiation shielding effectiveness in LEO.

We compare models of radiation transport and biological response to physical and biological dosimetry results from astronauts on the Mir space station. Transport models are shown to be in good agreement with physical measurements and indicate that the ratio of equivalent dose from the Galactic Cosmic Rays (GCR) to protons is about 3/2:1 and that this ratio will increase for exposures to internal organs. Two biological response models are used to compare to the Mir biodosimetry for chromosome aberration in lymphocyte cells; a track-structure model and the linear-quadratic model with linear energy transfer (LET) dependent weighting coefficients. These models are fit to in vitro data for aberration formation in human lymphocytes by photons and charged particles. Both models are found to be in reasonable agreement with data for aberrations in lymphocytes of Mir crew members: however there are differences between the use of LET dependent weighting factors and track structure models for assigning radiation quality factors. The major difference in the models is the increased effectiveness predicted by the track model for low charge and energy ions with LET near 10 keV/micrometers. The results of our calculations indicate that aluminum shielding, although providing important mitigation of the effects of trapped radiation, provides no protective effect from the galactic cosmic rays (GCR) in low-earth orbit (LEO) using either equivalent dose or the number of chromosome aberrations as a measure until about 100 g/cm 2 of material is used.

Chromosome Aberrations↗
PubMed2000

Bcl-w expression in colorectal adenocarcinoma.

We have found that the anti-apoptotic Bcl-2 family protein, Bcl-w, was frequently expressed in colorectal adenocarcinomas, with 69/75 showing positive staining with anti-Bcl-w IgG. Adenomas demonstrated a much lower frequency of Bcl-w expression (only 1 of 17), as did adenocarcinomas from other epithelial tissues such as breast (0/8), stomach (1112) and cervix (0/12). Bcl-w status could be related to the histopathological classification of the tumours, with TNM stage III tumours showing significantly higher levels of expression than tumours of better prognostic grade (at P = 0.009). Those patients with node involvement also had tumours with significantly elevated levels of Bcl-w (at P = 0.02), compared to those which were node-negative. The results suggest that Bcl-w could play a general role in the progression from adenoma to adenocarcinoma in the colorectal epithelium. Currently, more data are being collected to allow us to assess the importance of Bcl-w for disease progression and patient survival.

Adenocarcinoma↗
PubMed2000

In vivo modulation of CYP enzymes by quinidine and rifampin.

BACKGROUND: The metabolism of drugs and other xenobiotics is mediated by enzymes whose activities can be modulated by different compounds. The activities of these modulators have the potential to be used to optimize drug action, prevent toxicity, or identify the enzymes involved in a reaction. This approach requires that selective agents be used for specific enzymes. However, selectivity of action has been poorly characterized in vivo. METHODS: This study investigated the effect of 3 and 28 days of treatment with quinidine (200 mg daily) and rifampin (INN, rifampicin) (600 mg daily) on the activities of four cytochrome P450 enzymes and N-acetyltransferase in 28 healthy young male volunteers divided into three groups with a cocktail of drug probes used, including caffeine, mephenytoin, debrisoquin (INN, debrisoquine), and dapsone. RESULTS: Quinidine selectively and almost completely inhibited the activity of CYP2D6 from day 3 through day 28 without affecting any other enzymes. Rifampin showed evidence of time-dependent induction of the activities of all measured oxidative routes of metabolism but decreased the acetylation ratio in fast acetylators. The quinidine/rifampin combination resulted in selective CYP2D6 inhibition and induction of all other enzymes evaluated over this time period, suggesting that predictable complex interactions occur with the drug combination. CONCLUSIONS: These observations illustrate the value of simultaneous assessment of the effect of modulators on the activities of multiple specific enzymes with the drug cocktail approach.

Acetylation↗