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Biomedical subjects

T L Wilson

Publications and source records attributed to T L Wilson.

At least 19 recordsLinked to original sources

The FLUKA code for space applications: recent developments.

The FLUKA Monte Carlo transport code is widely used for fundamental research, radioprotection and dosimetry, hybrid nuclear energy system and cosmic ray calculations. The validity of its physical models has been benchmarked against a variety of experimental data over a wide range of energies, ranging from accelerator data to cosmic ray showers in the earth atmosphere. The code is presently undergoing several developments in order to better fit the needs of space applications. The generation of particle spectra according to up-to-date cosmic ray data as well as the effect of the solar and geomagnetic modulation have been implemented and already successfully applied to a variety of problems. The implementation of suitable models for heavy ion nuclear interactions has reached an operational stage. At medium/high energy FLUKA is using the DPMJET model. The major task of incorporating heavy ion interactions from a few GeV/n down to the threshold for inelastic collisions is also progressing and promising results have been obtained using a modified version of the RQMD-2.4 code. This interim solution is now fully operational, while waiting for the development of new models based on the FLUKA hadron-nucleus interaction code, a newly developed QMD code, and the implementation of the Boltzmann master equation theory for low energy ion interactions.

Computer Simulation↗

Vulnerability to flooding: health and social dimensions.

This paper presents research results on the impacts that floods can have on the people affected, thus complementing the existing data on the monetary losses liable to occur in flood events. Both datasets should be used when deciding on investment in flood defence measures. We report on research on the vulnerability of flood-affected communities to adverse health effects, and the development of an index of community vulnerability based on extensive focus-group research and secondary-source census data.

Disasters↗

The search for extraterrestrial intelligence.

As far as we know, humanity is alone in the Universe: there is no definite evidence for the existence of extraterrestrial life, let alone extraterrestrial civilizations (ETCs) capable of communicating or travelling over interstellar distances. Yet popular speculation about the existence of ETCs abounds, including reports of alien visitations either now or in the past. But there is a middle way. It is now possible to put limits on the existence of ETCs of varying capabilities, within arbitrary distances from the Solar System, and conceive of real-world strategies whereby we might communicate with ETCs, or they with us.

Exobiology↗

Cytokine production consequent to T cell--microglia interaction: the PMA/IFN gamma-treated U937 cells display similarities to human microglia.

Cognate interactions between human adult microglia and activated T lymphocytes induce the production of inflammatory cytokines. Since this interaction can occur in a non-antigen-dependent manner, it is relevant to a variety of CNS diseases where activated T cells, regardless of specificities, come into contact with microglia; these disorders include multiple sclerosis, trauma, stroke and Alzheimer's disease. A model cell line would facilitate studies of the engagement between T cells and human adult microglia, since the latter are difficult to obtain in substantial quantity or frequency. This study shows that the PMA/IFN gamma-treated U937 cell line shows similarities to microglia in its interaction with activated T lymphocytes, in that the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-10 and IL-12 is induced. Morphological features and mechanisms of cytokine production resemble those observed in microglia--T cell co-cultures since CTLA-4 and CD40--CD40L blockades reduce TNF-alpha and IL-10 levels, while anti-CD23 inhibits IL-10 only in U937--T cell interactions. We propose that PMA/IFN gamma-treated U937 cells can serve as a model of human adult microglia to study cytokine generation in response to interactions with activated T cells.

Antibodies↗

Development of a space radiation Monte Carlo computer simulation based on the FLUKA and ROOT codes.

This NASA funded project is proceeding to develop a Monte Carlo-based computer simulation of the radiation environment in space. With actual funding only initially in place at the end of May 2000, the study is still in the early stage of development. The general tasks have been identified and personnel have been selected. The code to be assembled will be based upon two major existing software packages. The radiation transport simulation will be accomplished by updating the FLUKA Monte Carlo program, and the user interface will employ the ROOT software being developed at CERN. The end-product will be a Monte Carlo-based code which will complement the existing analytic codes such as BRYNTRN/HZETRN presently used by NASA to evaluate the effects of radiation shielding in space. The planned code will possess the ability to evaluate the radiation environment for spacecraft and habitats in Earth orbit, in interplanetary space, on the lunar surface, or on a planetary surface such as Mars. Furthermore, it will be useful in the design and analysis of experiments such as ACCESS (Advanced Cosmic-ray Composition Experiment for Space Station), which is an Office of Space Science payload currently under evaluation for deployment on the International Space Station (ISS). FLUKA will be significantly improved and tailored for use in simulating space radiation in four ways. First, the additional physics not presently within the code that is necessary to simulate the problems of interest, namely the heavy ion inelastic processes, will be incorporated. Second, the internal geometry package will be replaced with one that will substantially increase the calculation speed as well as simplify the data input task. Third, default incident flux packages that include all of the different space radiation sources of interest will be included. Finally, the user interface and internal data structure will be melded together with ROOT, the object-oriented data analysis infrastructure system. Beyond the benefits of 'objectivity', ROOT's incorporation will also provide a graphical user interface with powerful tools for input prior to the calculation, as well as for data analysis and visualization of the results.

Computer Simulation↗

Elevated zinc induces siderophore biosynthesis genes and a zntA-like gene in Pseudomonas fluorescens.

Zinc-regulated genes were analyzed in Pseudomonas fluorescens employing mutagenesis with a reporter gene transposon. Six mutants responded with increased gene expression to elevated concentrations of zinc. Genetic and biochemical analysis revealed that in four of the six mutants the transposon had inserted into genes essential for the biosynthesis of the siderophore pyoverdine. The growth of one of the mutants was severely impaired in the presence of elevated concentrations of cadmium and zinc ions. In this mutant, the transposon had inserted in a gene with high similarity to P-type ATPases involved in zinc and cadmium ion transport. Four mutants reacted with reduced gene expression to elevated concentrations of zinc. One of these mutants was sensitive to zinc, cadmium and copper ions. The genetic region targeted in this mutant did not show similarity to any known gene.

Adenosine Triphosphatases↗

Cadmium-regulated gene fusions in Pseudomonas fluorescens.

To study the mechanisms soil bacteria use to cope with elevated concentrations of heavy metals in the environment, a mutagenesis with the lacZ-based reporter gene transposon Tn5B20 was performed. Random gene fusions in the genome of the common soil bacterium Pseudomonas fluorescens strain ATCC 13525 were used to create a bank of 5,000 P. fluorescens mutants. This mutant bank was screened for differential gene expression in the presence of the toxic metal cadmium. Fourteen mutants were identified that responded with increased or reduced gene expression to the presence of cadmium. The mutants were characterized with respect to their metal-dependent gene expression and their metal tolerance. Half the identified mutants reacted with differential gene expression specifically to the metal cadmium, whereas some of the other mutants also responded to elevated concentrations of copper and zinc ions. One of the mutants, strain C8, also showed increased gene expression in the presence of the solvent ethanol, but otherwise no overlap between cadmium-induced gene expression and general stress response was detected. Molecular analysis of the corresponding genetic loci was performed using arbitrary polymerase chain reaction (PCR), DNA sequencing and comparison of the deduced protein products with sequences deposited in genetic databases. Some of the genetic loci targeted by the transposon did not show any similarities to any known genes; thus, they may represent 'novel' loci. The hypothesis that genes that are differentially expressed in the presence of heavy metals play a role in metal tolerance was verified for one of the mutants. This mutant, strain C11, was hypersensitive to cadmium and zinc ions. In mutant C11, the transposon had inserted into a genetic region displaying similarity to genes encoding the sensor/regulator protein pairs of two-component systems that regulate gene expression in metal-resistant bacteria, including czcRS of Ralstonia eutropha, czrRS of Pseudomonas aeruginosa and copRS of Pseudomonas syringae. Although the P. fluorescens strain used in this study had not been isolated from a metal-rich environment, it nevertheless contained at least one genetic region enabling it to cope with elevated concentrations of heavy metals.

Artificial Gene Fusion↗

Functional outcome following surgical treatment of intra-articular distal humeral fractures through a posterior approach.

BACKGROUND: While surgical repair is considered the standard of care of displaced intra-articular distal humeral fractures, most investigators have assessed its results with use of surgeon-based and/or radiograph-based outcome measures. The purpose of our study was to determine the functional outcome of fixation of displaced intra-articular distal humeral fractures with use of a standardized evaluation methodology consisting of objective testing of muscle strength and use of patient-based questionnaires (both limb-specific and general health-status questionnaires). METHODS: We identified twenty-five patients (fourteen male and eleven female), with a mean age of forty-seven years, who had an isolated, closed, displaced, intercondylar, intra-articular fracture of the distal part of the humerus repaired operatively through a posterior approach and fixed with plates on both the medial and the lateral column. All patients returned for follow-up that included recording of a complete history, physical examination, radiographic examination, completion of both a limb-specific questionnaire (Disabilities of the Arm, Shoulder and Hand [DASH]) and a general health-status questionnaire (Short Form-36 [SF-36]), and objective muscle-strength testing. RESULTS: The mean duration of follow-up was thirty-seven months (range, eighteen to seventy-five months). The mean flexion contracture was 25 degrees (range, 5 to 65 degrees), and the mean arc of flexion-extension was 108 degrees (range, 55 to 140 degrees). Significant decreases in mean muscle strength compared with that on the normal side were seen in both elbow flexion measured at 90 degrees (74 percent of normal, p = 0.01) and elbow extension measured at 45 degrees (76 percent of normal, p = 0.01), 90 degrees (74 percent of normal, p = 0.01), and 120 degrees (75 percent of normal, p = 0.01). The mean DASH score was 20 points, indicating mild residual impairment. The SF-36 scores revealed minor but significant decreases in the role-physical and physical function scores (p = 0.01 and 0.03, respectively) but no alteration of the mental component or mean scores. Six patients (24 percent) had a reoperation; three of them had removal of prominent hardware used to fix the site of an olecranon osteotomy. CONCLUSIONS: The surgical repair of an intra-articular distal humeral fracture is an effective procedure that reliably maintains general health status as measured by patient-based questionnaires. Our study quantified a decrease in the range of motion and muscle strength of these patients, which may help to explain the mild residual physical impairment detected by the limb-specific outcome measures and physical function components of the general health-status measures.

Adult↗

Reduction of shock-induced gastric damage by a nitric oxide-releasing aspirin derivative: role of neutrophils.

The gastric damage associated with hemorrhagic shock appears to occur, at least in part, through neutrophil-dependent mechanisms. Nitric oxide (NO)-releasing derivatives of aspirin have been shown to spare the gastrointestinal tract of injury. As NO can inhibit neutrophil adherence, it is possible that such a derivative of aspirin (NCX-4016) would exert inhibitory effects on neutrophil adherence and therefore be capable of protecting the stomach against shock-induced gastric damage. This hypothesis was tested in this study. Oral administration of NCX-4016 or glyceryl trinitrate or depletion of circulating neutrophils with antineutrophil serum significantly reduced the extent of gastric damage induced by hemorrhagic shock, whereas aspirin had no effect. NCX-4016 and antineutrophil serum pretreatment resulted in significant preservation of gastric blood flow during the shock period. Moreover, NCX-4016, but not aspirin, was capable of inhibiting N-formyl-Met-Leu-Phe-induced leukocyte adherence to postcapillary mesenteric venules. These results suggest that an NO-releasing aspirin derivative reduces the susceptibility of the stomach to shock-induced damage through inhibitory effects on neutrophil adherence to the vascular endothelium.

Animals↗

Noninvasive measurements of albumin flux into lung interstitium with increased microvascular pressure.

The purpose of this study was to determine the effect of increasing left atrial pressure on noninvasive measurements of radiolabeled albumin normalized slope index (NSI). Using portable gamma scintillation detectors, we monitored radioactivities of 131I-labeled albumin and 51Cr-labeled red blood cells in the blood and over the lung of six anesthetized sheep before and 2 h after a 9- to 14-Torr increase in left atrial pressure. Measurements of NSI for 131I-albumin decreased > 50% after a step increase in left atrial pressure. We interpreted the data using a model that has been used to successfully describe unsteady-state lymph flow and protein concentrations after vascular pressure increases in sheep. Model predictions strongly suggest that the reduction in NSI is due to rapid fluid and solute removal from the interstitium via the lymphatics. The theoretical model was able to predict external scan data and lung lymph protein concentrations only when a change in lymphatic conductance (LI) or initial lymphatic pressure (P0) was imposed at the time of increased pressure. On average, model-predicted increases in LI were sevenfold, whereas predicted decreases in P0 were four- to fivefold. Imposed changes in LI and P0 opposed increases in interstitial fluid volume after increased pressure. This was consistent with normal-to-low postmortem measurements of bloodless wet-to-dry lung weight ratios. In summary, these results indicate that changes in the rate of fluid removal from the interstitium can significantly alter NSI, and in this case, NSI does not reflect pulmonary microvascular permeability. In sheep, increases in the lymphatics' ability to remove interstitial fluid may occur with relatively small increases in microvascular pressure.

Animals↗

Noninvasive measures of radiolabeled dextran transport in in situ rabbit lung.

UNLABELLED: Dextrans are nontoxic and can be obtained in a wide variety of molecular weights. The purpose of this study was to label 6-kDa and 40-kDa dextrans with gamma- (99mTc) and positron- (18F) emitting radioisotopes and monitor their transport across the pulmonary microvascular barrier. METHODS: External scan measurements for radiolabeled uncharged dextrans, albumin and red blood cells were obtained in eight blood-perfused in situ rabbit lung preparations. After 3 hr of external scanning, the lungs were removed for postmortem and extravascular distribution volume calculations. Extravascular distribution volumes were obtained in six additional rabbits following 4 hr of dextran perfusion to compare the effect of time. The normalized slope index (NSI), a measure of transvascular transport rate, was calculated for each diffusible tracer. RESULTS: The mean NSI for albumin (0.001676 +/- 0.000537 min-1) was significantly lower than NSI for the 40-kDa dextran (0.002303 +/- 0.0005426 min-1) as well as the 6-kDa dextran (0.004312 +/- 0.001134 min-1). The difference between the 6-kDa and the 40-kDa dextrans was also significant. After 4 hr of equilibration, distribution volumes were not significantly different than those obtained at 3 hr. CONCLUSION: Dextrans can be radiolabeled with gamma and positron emitters and small dextrans traverse the lung microvascular barrier more rapidly than albumin. Our results suggest that the use of small dextrans rather than albumin can reduce scan times in clinical applications and minimize motion artifact associated with the noninvasive gamma detection method.

Animals↗

A voice-operated method for administering the MMPI.

Paper/pencil psychological tests such as the Minnesota Multiphasic Personality Inventory (MMPI) are difficult to complete independently by patients with limited hand function. This paper describes a voice recognition system developed to allow patients with no hand function to take the MMPI independently. Profiles generated by this system are not statistically different from those generated by standard MMPI booklet format. Limitations and possible extensions of the system as it currently exists are discussed.

Journal Article↗

follicular fluid electrolytes and osmolality in cyclic pigs.

Sodium and osmolar concentrations of porcine folliclar fluid in the cyclic pig did not vary significantly during the oestrous cycle, and were similar to those in plasma. The K+ concentration was greater in small (Days 12-13) and medium-sized (Day 16) follicles than in plasma or large (Day 18-oestrus) follicles of cyclic sows. In contrast, follicular fluid obtained from slaughterhouse material had higher potassium and osmolality, and lower sodium values, which are assumed to be due to post-mortem changes.

Animals↗

Effect of protein on titrimetry of bicarbonate, titratable acid, and ammonium in urine.

Measurement of bicarbonate, titratable acid (HTA+) and ammonium in the urine can facilitate clinical evaluation of acid-base status. Sequential measurement of these three components by titrimetric techniques is well established, but possible interference by proteinuria has not been examined. We report the influence on these analyses of albumin and globulin, two proteins commonly observed in urine in renal disease states. The presence of these proteins in urine affects the measurement of NH4+, and to a less extent that of HTA+. The magnitude of the effect depends on the concentration and the kind of protein present. Proteins do not influence the measurement of HCO3-.

Acid-Base Equilibrium↗

Intracellular pH in cold-blooded vertebrates as a function of body temperature.

Intracellular pH (pHi) was measured in vivo in tissue of frogs (Rana catesbeiana) and turtles (Pseudemys scripta) using the DMO technique. Animals were permitted 3-8 days to come to a new steady-state body temperature (Tb) which ranged 5-32 degrees C. Least squares regression equation for pHi data are: frog blood, 8.184-0.0206 Tb; frog striated muscle, 7.275-0.0152 Tb; turtle blood, 8.092-0.0207Tb; turtle muscle, 7.421-0.0186 Tb; turtle heart, 7.452-0.0122 Tb; turtle liver, 7.753-0.0233 Tb; turtle esophageal smooth muscle, 7.513-0.0141 Tb. Only turtle cardiac muscle deltapHi/deltaT was significantly different from deltapH/deltaT of blood. Results have been interpreted in terms of protein charge state alterations; in the physiological pH range, histidine residues of proteins are the principal dissociable groups (HPr+ = H+ + Pr) affected by pHi and Tb changes. Constancy of protein charge state can be assessed by monitoring alpha imidazole, alphaIM = Pr/(HPr+ + Pr). A uniform pKIM of 6.85 (20degreesC) and a deltaHO of 7 kcal/mol are assumed in calculating alphaIM. Intracellular alphaIM is preserved in the tissues studied as body temperature changes. These results indicate that ectotherm acid-base balance, alphastat control, regulates not only extracellular blood proteins, but also intracellular compartment proteins in such a way as to preserve functions dependent upon protein net charge states.

Acid-Base Equilibrium↗