Search PubMed⌕ Search

Biomedical subjects

J W Wilson

Publications and source records attributed to J W Wilson.

At least 109 records · Page 6Linked to original sources

Accurate universal parameterization of absorption cross sections II--neutron absorption cross sections.

A recent parameterization (here after referred as paper I, Ref. [4]) of absorption cross sections for any system of charged ions collisions including proton -nucleus collisions, is extended for neutron-nucleus collisions valid from approximately 1 MeV to a few GeV, thus providing a comprehensive picture of absorption cross sections for any system of collision pair (charged and/or uncharged). The parameters are associated with the physics of the problem. At lower energies, the optical potential at the surface is important and the Pauli operator plays an increasingly important role at intermediate energies. The agreement between the calculated and experimental data is better than earlier published results.

Elementary Particle Interactions↗

Beta 2-adrenoceptor agonist-mediated inhibition of human airway smooth muscle cell proliferation: importance of the duration of beta 2-adrenoceptor stimulation.

1. Airway hyperresponsiveness in asthma has been ascribed to airway wall thickening as a result of smooth muscle proliferation and hypertrophy. We have previously shown that continuous exposure to the beta 2-adrenoceptor agonist, salbutamol inhibits mitogen-induced proliferation of airway smooth muscle cells. In the present study, the effects of variable durations and repeated periods of exposure to beta 2-adrenoceptor agonists on DNA synthesis in human cultured airway smooth muscle have been investigated to model some of the possible pharmacokinetic profiles of these agents following inhalation. DNA synthesis was measured by [3H]-thymidine incorporation. 2. Shorter periods of exposure (up to 2.5 h) of airway smooth muscle cells to salbutamol (100 nM) commencing 30 min before thrombin (0.3 u ml-1) stimulation had no effect on the subsequent increase in [3H]-thymidine incorporation. However, inhibition by salbutamol was evident with a 4.5 h exposure and was maximal after an 8.5 h exposure. Similar patterns of results were observed when fenoterol (100 nM) was used in place of salbutamol as the beta 2-adrenoceptor agonist or when epidermal growth factor (300 pM) was used in place of thrombin as the mitogen. Salbutamol had no effect on thrombin-stimulated [3H]-leucine incorporation after 8.5 h of exposure, but a statistically significant effect was observed after 48 h of exposure. 3. Experiments in which DNA synthesis was measured up to 52 h after the addition of thrombin indicated that exposure to salbutamol during the first 8 h of mitogen stimulation delayed rather than inhibited the DNA synthesis. 4. Addition of salbutamol (100 nM) at different times either before or up to 24 h after the addition of thrombin indicated that [3H]-thymidine incorporation (measured between 24 and 28 h after thrombin) could be significantly attenuated when salbutamol was added as late as 18 h after the addition of thrombin. 5. The effects of more prolonged exposure to salbutamol were investigated by the addition of salbutamol for either 15 or 24 h per day for a total of 3 days. There were no significant differences in the level of inhibition of thrombin-stimulated [3H]-thymidine incorporation between continuous and intermittent salbutamol over the 3 day period and the inhibition was also not different to that achieved with a single continuous exposure to salbutamol over 28 h. 6. These results indicate that although exposure to beta 2-adrenoceptor agonists during the first 8 h of mitogen stimulation does not have a sustained inhibitory effect on DNA synthesis, repeated intermittent or prolonged continuous exposures to salbutamol do inhibit DNA synthesis, without evidence of marked desensitization.

Adrenergic beta-2 Receptor Agonists↗

The kilE locus of promiscuous IncP alpha plasmid RK2 is required for stable maintenance in Pseudomonas aeruginosa.

Eight coordinately regulated operons constitute the kor regulon of the IncP alpha plasmid RK2. Three operons specify functions required for replication initiation, conjugative transfer, and control of gene expression. The functions of the other operons, including those of the four coregulated operons that compose the kilA, kilC, and kilE loci, have not been determined. Here, we present the first evidence that a kil determinant is involved in IncP plasmid maintenance. Elevation of KorC levels specifically to reduce the expression of the KorC-regulated kilC and kilE operons severely affected the maintenance of both the IncP alpha plasmid RK2lac and the IncP beta plasmid R751 in Pseudomonas aeruginosa but had little effect on plasmid maintenance in Escherichia coli. Precise deletion of the two kilE operons from RK2lac was achieved with the VEX mutagenesis system for large genomes. The resulting plasmid showed significant loss of stability in P. aeruginosa only. The defect could be complemented by reintroduction of kilE at a different position on the plasmid. The instability of the RK2lac delta kilE mutant did not result from a reduction in average plasmid copy number, reduced expression of kilC, decreased conjugative transfer, or loss of the korE regulator. We found that both the par and kilE loci are required for full stability of RK2lac in P. aeruginosa and that the par and kilE functions act independently. These results demonstrate a critical role for the kilE locus in the stable inheritance of RK2 in P. aeruginosa.

Bacterial Proteins↗

Immunopathological changes in the airways of stable lung transplant recipients.

BACKGROUND: Pathological obliterative bronchiolitis, characterised by inflammation and occlusion of airways, is a serious complication of lung transplantation. Endobronchial biopsy (EBB) provides a means of examining transplanted airways. This study aimed to investigate the role of EBB samples in revealing early signals of airway injury. METHODS: In 18 stable lung transplant recipients with close to maximal lung function (median FEV1, best after transplantation 100%, interquartile range 98-100%) EBB samples were taken simultaneously with transbronchial biopsy samples and bronchoalveolar lavage (BAL) fluid (median 195 days after transplantation). OCT embedded specimens were snap frozen on an isopentane slurry made with liquid nitrogen and 7 microns sections were stained with monoclonal antibodies using a three stage immunoperoxidase method. RESULTS: Compared with nine non-transplanted control subjects, EBB specimens from the stable transplant group had significantly increased CD8 positivity (median 53 versus 27 cells/mm basement membrane, p = 0.04; 95% CI for the difference 1 to 46)) and increased HLA-DR positivity (median 84 versus 26 cells/mm basement membrane, 95% CI for the difference 6 to 115). There was an increase in CD68 positive cells in the EBB specimens from transplant recipients of borderline significance (median 92 versus 68, p = 0.08, 95% CI for the difference 1 to 84). CD3, CD4, and CD25 counts were similar in the two groups. EBB findings were not influenced by age, sex, indication for transplant, immunosuppression doses or levels, nor the presence of airway commensals in the BAL fluid. CONCLUSIONS: EBB is practicable in a transplant setting and provides information about bronchial inflammatory changes. It is likely that there is ongoing inflammation, possibly rejection mediated, even in healthy lung transplant recipients despite triple immunosuppression.

Adult↗

Scar collagen deposition in the airways of allografts of lung transplant recipients.

Collagen subtype deposition has not been studied in the airways of transplanted lungs. As part of rejection, a series of immunologic insults results in a remodeling of the allograft. In chronic rejection, changes in the airway leading to obliterative bronchiolitis syndrome (OBS) are particularly important. To better understand the mechanism of OBS occurring in chronic lung rejection, we investigated deposition of three fibrillar collagens (type I, III, V) in airway biopsies of lung allografts taken from 10 clinically well lung transplant recipients (wLTR) and eight lung transplant recipients (LTR) with OBS (OBLTR) using an immunoperoxidase method. Collagen III deposition and the ratio of collagen type III to type I were found to be significantly increased in OBLTR compared with wLTR (p < 0.05), and the latter correlated inversely with both FEF(25-75) (r = -0.69; p < 0.05) and FEV1 (r = 0.62; p = 0.05) in OBLTR. This suggests that an increased proportion of collagen III in the airway walls of transplanted lungs might be an early signal of the progression to terminal chronic lung allograft dysfunction. The changes in the ratio of type III to type I collagen in the airways of lung allografts may provide important insights into the process of airway remodeling in chronic lung rejection.

Adult↗

Increased vascularity of the bronchial mucosa in mild asthma.

Airway-wall remodeling leading to thickening of the bronchial wall in asthma has been invoked to account for airflow obstruction and increased bronchial reactivity to provocative stimuli. Bronchial-wall changes characteristic of asthma are thought to include increased vascularity with vasodilatation. The contention that inflammatory mediators cause bronchial vasodilatation and that growth factors may induce increased vascularity is based on little structural evidence. We took bronchoscopic biopsies from the major airways of 12 subjects with mild asthma and 11 control subjects, and evaluated bronchial vessel numbers and size, using computerized image analysis after staining for type IV collagen in vessel walls. The airways of asthmatic subjects were significantly more vascular (17.2 +/- 4.2 versus 10.3 +/- 1.9%, p < 0.001), with more vessels (738 +/- 150 versus 539 +/- 276 vessels/mm2 [mean +/- SD], p < 0.05) than those of the controls. There were significantly more asthmatic bronchial than control vessels with a cross-sectional area greater than 300 microns2 (19.4 versus 12.7%, p < 0.05). These findings provide the first confirmatory evidence that bronchial biopsies from patients with mild asthma are more vascular than those of normal controls, that there are more vessels in asthmatic airways, and that asthmatic bronchial vessels are larger than controls.

Asthma↗

The measurement of reticular basement membrane and submucosal collagen in the asthmatic airway.

BACKGROUND: An increase in types III and V collagen below the bronchial epithelium of the airway is known to be responsible for apparent thickening of the reticular basement membrane (RBM) and is recognized as a characteristic feature of asthma. Wide variations exist in reported ranges of the thickness of the RBM in both asthmatic and control airways. The description of collagen deposition has been confined to the RBM with no previous reports of increased collagen deeper within the bronchial wall (i.e. submucosa), although inflammation is known to extend to deeper levels. OBJECTIVE: The objective of this study was to compare different methods used to measure RBM thickness and to examine collagen deposition in deeper asthmatic bronchial submucosa. METHODS: We examined bronchial mucosal biopsies from 15 asthmatic and 13 normal healthy controls to measure RBM thickness by light and electron microscopic methods on resin sections and to estimate the extent of collagen deposition in the submucosa by immunochemical staining with monoclonal antibodies to collagen subtypes on paraffin sections. RESULTS: Simple staining with toluidine blue on resin sections coupled with light microscopic evaluation was as accurate and less expensive than electron microscopic methods in the measurement of the thickness of RBM (mean +/- SD, light microscopy: asthma vs control, 6.01 +/- 2.09 vs 3.19 +/- 0.55 microns, P < 0.001; electron microscopy: asthma vs control, 6.09 +/- 2.19 vs 2.85 +/- 0.86 microns, P < 0.01). Using monoclonal antibodies to collagen subtypes and image analysis methods, we identified increased collagen in the submucosa in asthma (type III collagen, asthma vs control: 62 +/- 7 vs 51 +/- 9%, P < 0.05, type V collagen, asthma vs control: 60 +/- 6 vs 52 +/- 9%, P < 0.05). CONCLUSIONS: This study has demonstrated that the RBM may be reliably measured by light microscopic methods. This study shows for the first time that the submucosa of the asthmatic airway contains significantly more collagen than normal controls, giving rise to the possibility that airway scar formation may have greater functional implications than has been previously believed from consideration of the RBM alone.

Adolescent↗

Effect of influenza A virus infection on natural and adaptive cellular immunity.

Influenza A virus (FLU) is an important pathogen in humans. Although many features of the antiviral immune response have been elucidated in murine and human models of disease, little is known about the role of NK cells, which provide natural, innate immunity. The effects of experimental intranasal FLU (H1N1) inoculation on NK cells and other immune parameters were studied in 18 healthy, adult volunteers during the acute and convalescent phases of infection. Peripheral blood mononuclear cells (PBMNC) were assayed at baseline and on Postinoculation Days 1, 3, 4, 6, 7, 23, and 44. FLU infection and pathophysiologic upper airway responses were documented in all subjects, and there was no mortality. During both the acute (Days 1-3) and the convalescent (Days 23 and 44) stages of the FLU infection, significant increases in NK activity and decreases in the number of activated NK cells were observed. Reductions in the absolute number of T lymphocytes and in PBMNC proliferation to FLU virus antigen and mitogen were also observed. The current investigation extended those findings to include reductions in the number of CD4+ and CD8+ T lymphocytes and increases in the number of activated T lymphocytes. These results document that FLU infection was accompanied by enhancement of natural immunity and, as expected, suppression of most of the other measured parameters of cellular immunity. The normal response to FLU infection in humans may involve sequential modulation of the different components of the cellular immune system.

Adult↗

Accurate universal parameterization of absorption cross sections.

We present a simple universal parameterization of total reaction cross sections for any system of colliding nuclei valid for the entire energy range from a few A MeV to a few A GeV. The universal picture presented here treats the proton-nucleus collision as a special case of the nucleus-nucleus collision, where the projectile has charge and mass number one. The parameters are associated with the physics of the collision system. In general terms Coulomb interaction modifies cross sections at lower energies and the effects of Pauli blocking are important at higher energies. The agreement between the calculated and experimental data is better than all earlier published results.

Alpha Particles↗

Shielding against galactic cosmic rays.

Ions of galactic origin are modified but not attenuated by the presence of shielding materials. Indeed, the number of particles and the absorbed energy behind most shield materials increases as a function of shield thickness. The modification of the galactic cosmic ray composition upon interaction with shielding is the only effective means of providing astronaut protection. This modification is intimately connected with the shield transport properties and is a strong function of shield composition. The systematic behavior of the shield properties in terms of microscopic energy absorption events will be discussed. The shield effectiveness is examined with respect to conventional protection practice and in terms of a biological endpoint: the efficiency for reduction of the probability of transformation of shielded C3H10T1/2 mouse cells. The relative advantage of developing new shielding technologies is discussed in terms of a shield performance as related to biological effect and the resulting uncertainty in estimating astronaut risk.

Aluminum↗

Light ion components of the galactic cosmic rays: nuclear interactions and transport theory.

Light nuclei are present in the primary galactic cosmic rays (GCR) and are produced in thick targets due to projectile or target fragmentation from both nucleon and heavy ion induced reactions. In the primary GCR, 4He is the most abundant nucleus after 1H. However, there are also a substantial fluxes of 2H and 3He. In this paper we describe theoretical models based on quantum multiple scattering theory for the description of light ion nuclear interactions. The energy dependence of the light ion fragmentation cross section is considered with comparisons of inclusive yields and secondary momentum distributions to experiments described. We also analyze the importance of a fast component of lights ions from proton and neutron induced target fragmentation. These theoretical models have been incorporated into the cosmic ray transport code HZETRN and will be used to analyze the role of shielding materials in modulating the production and the energy spectrum of light ions.

Cosmic Radiation↗

Effects of orbit progression on the radiation exposures from solar proton fluxes in low Earth orbit under geomagnetic storm conditions.

The present study examines the effects of orbit progression on the exposures within a Space Station Freedom module in a 51.6-degree inclined orbit at 450 km. The storm evolution is modeled after the November 1960 event, and the solar proton flux evolution is taken from the August 1972 solar proton event. The effects of a strong magnetic shock, such as was observed during the October 1989 event, is also modeled. The statistics on hourly average storm fields for the last forty years reveal that the largest geomagnetic storms approach a Dst value of -500 nanotesla at the storm peak. Similarly, one of the largest satellite-measured proton flux (> 10 MeV) for space exposures is the event of August 1972. The effects of orbit progression (advance of the line of nodes) is examined for the above conditions to study the variation of exposures under differing times of occurrence of the solar proton peak intensity, attainment of geomagnetic storm maximum, and the location of the line of nodes of the last geomagnetically protected orbit. The impact of the inherent inhomogeneity of the space station module is examined as a limiting factor on exposure with regard to the need of additional parasitic shielding.

Algorithms↗

Measurements of the linear energy transfer spectra on the Mir orbital station and comparison with radiation transport models.

A tissue equivalent proportional counter designed to measure the linear energy transfer spectra (LET) in the range 0.2-1250 keV/micrometer was flown in the Kvant module on the Mir orbital station during September 1994. The spacecraft was in a 51.65 degrees inclination, elliptical (390 x 402 km) orbit. This is nearly the lower limit of its flight altitude. The total absorbed dose rate measured was 411.3 +/- 4.41 microGy/day with an average quality factor of 2.44. The galactic cosmic radiation (GCR) dose rate was 133.6 microGy/day with a quality factor of 3.35. The trapped radiation belt dose rate was 277.7 microGy/day with an average quality factor of 1.94. The peak rate through the South Atlantic Anomaly was approximately 12 microGy/min and nearly constant from one pass to another. A detailed comparison of the measured LET spectra has been made with radiation transport models. The GCR results are in good agreement with model calculations; however, this is not the case for radiation belt particles and again points to the need for improving the AP8 omni-directional trapped proton models.

Brazil↗

Effects of target fragmentation on evaluation of LET spectra from space radiations: implications for space radiation protection studies.

We present calculations of linear energy transfer (LET) spectra in low earth orbit from galactic cosmic rays and trapped protons using the HZETRN/BRYNTRN computer code. The emphasis of our calculations is on the analysis of the effects of secondary nuclei produced through target fragmentation in the spacecraft shield or detectors. Recent improvements in the HZETRN/BRYNTRN radiation transport computer code are described. Calculations show that at large values of LET (> 100 keV/micrometer) the LET spectra seen in free space and low earth orbit (LEO) are dominated by target fragments and not the primary nuclei. Although the evaluation of microdosimetric spectra is not considered here, calculations of LET spectra support that the large lineal energy (y) events are dominated by the target fragments. Finally, we discuss the situation for interplanetary exposures to galactic cosmic rays and show that current radiation transport codes predict that in the region of high LET values the LET spectra at significant shield depths (> 10 g/cm2 of Al) is greatly modified by target fragments. These results suggest that studies of track structure and biological response of space radiation should place emphasis on short tracks of medium charge fragments produced in the human body by high energy protons and neutrons.

Aluminum↗

Effects of track structure and cell inactivation on the calculation of heavy ion mutation rates in mammalian cells.

It has long been suggested that inactivation severely effects the probability of mutation by heavy ions in mammalian cells. Heavy ions have observed cross sections of inactivation that approach and sometimes exceed the geometric size of the cell nucleus in mammalian cells. In the track structure model of Katz the inactivation cross section is found by summing an inactivation probability over all impact parameters from the ion to the sensitive sites within the cell nucleus. The inactivation probability is evaluated using the dose-response of the system to gamma-rays and the radial dose of the ions and may be equal to unity at small impact parameters for some ions. We show how the effects of inactivation may be taken into account in the evaluation of the mutation cross sections from heavy ions in the track structure model through correlation of sites for gene mutation and cell inactivation. The model is fit to available data for HPRT mutations in Chinese hamster cells and good agreement is found. The resulting calculations qualitatively show that mutation cross sections for heavy ions display minima at velocities where inactivation cross sections display maxima. Also, calculations show the high probability of mutation by relativistic heavy ions due to the radial extension of ions track from delta-rays in agreement with the microlesion concept. The effects of inactivation on mutations rates make it very unlikely that a single parameter such as LET or Z*2/beta(2) can be used to specify radiation quality for heavy ion bombardment.

Animals↗

Microscopic optical model calculations of 4He, 12C-nucleus absorption cross sections.

Calculations of absorption cross sections using a microscopic first-order optical potential for heavy-ion scattering are compared with experiments. In-medium nucleon-nucleon (NN) cross sections were used to calculate the two-body scattering amplitude. A medium-modified first-order optical potential was obtained for heavy-ion scattering using the in-medium two-body scattering amplitude. A partial wave expansion of the Lippmann-Schwinger equation in momentum space was used to calculate the absorption cross sections for various systems. The results are presented for the absorption cross sections for 4He-nucleus and 12C-nucleus scattering systems and are compared with the experimental values in the energy range 18-83A MeV. The use of the in-medium NN cross sections is found to result in significant reduction of the free space absorption cross sections in agreement with experiment.

Carbon↗

Dose equivalent near the bone-soft tissue interface from nuclear fragments produced by high-energy protons.

During manned space missions, high-energy nucleons of cosmic and solar origin collide with atomic nuclei of the human body and produce a broad linear energy transfer spectrum of secondary particles, called target fragments. These nuclear fragments are often more biologically harmful than the direct ionization of the incident nucleon. That these secondary particles increase tissue absorbed dose in regions adjacent to the bone-soft tissue interface was demonstrated in a previous publication. To assess radiological risks to tissue near the bone-soft tissue interface, a computer transport model for nuclear fragments produced by high energy nucleons was used in this study to calculate integral linear energy transfer spectra and dose equivalents resulting from nuclear collisions of 1-GeV protons transversing bone and red bone marrow. In terms of dose equivalent averaged over trabecular bone marrow, target fragments emitted from interactions in both tissues are predicted to be at least as important as the direct ionization of the primary protons-twice as important, if recently recommended radiation weighting factors and "worst-case" geometry are used. The use of conventional dosimetry (absorbed dose weighted by aa linear energy transfer-dependent quality factor) as an appropriate framework for predicting risk from low fluences of high-linear energy transfer target fragments is discussed.

Bone Marrow↗