Search PubMed⌕ Search

Biomedical subjects

J W Wilson

Publications and source records attributed to J W Wilson.

At least 127 records · Page 7Linked to original sources
PubMed1996

A Green's function method for high charge and energy ion transport.

A heavy-ion transport code using Green's function methods is developed. The low-order perturbation terms exhibiting the greatest energy variation are used as dominant energy-dependent terms, and the higher order collision terms are evaluated using nonperturbative methods. The recently revised NUCFRG database is used to evaluate the solution for comparison with experimental data for 625A MeV 20Ne and 517A MeV 40Ar ion beams. Improved agreements with the attenuation characteristics for neon ions are found, and reasonable agreement is obtained for the transport of argon ions in water.

Argon↗
PubMed1996

The fragmentation of 510 MeV/nucleon iron-56 in polyethylene. II. Comparisons between data and a model.

The results of a Monte Carlo model for calculating fragment fluences and LET spectra are compared to data taken with 600 MeV/nucleon iron ions incident on an accelerator beamline configured for irradiation of biological samples, with no target and with 2, 5 and 8 cm of polyethylene. The model uses a multi-generation nuclear fragmentation code, coupled with a formulation of ionization energy loss based on the Bethe-Bloch equation. In the region where the data are reliable and the experimental acceptance is well understood, many of the features of the experimental spectra are well replicated by the model. To obtain good agreement with the experimental data, the model must allow for at least two generations of fragment production in the target.

Algorithms↗
PubMed1995

Salbutamol inhibits the proliferation of human airway smooth muscle cells grown in culture: relationship to elevated cAMP levels.

The link between increased usage of beta-adrenoceptor agonists and worsening of asthma symptoms has raised interest in the effects of agents such as salbutamol on airway wall remodelling, and particularly airway smooth muscle proliferation. In the present study we have investigated the role of increases in intracellular cAMP in the inhibitory effect of salbutamol on airway smooth muscle proliferation. The inhibitory effects of a combination of submaximally effective concentrations of salbutamol (10 nM) and the non-selective phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 100 microM) on thrombin (0.3 U/mL)-induced mitogenesis in human cultured airway smooth muscle cells was greater than that for either agent alone. In addition, agents known to increase cAMP-dependent protein kinase activity including forskolin (10 microM), 8-bromoadenosine-3',5'-cyclic monophosphate (100 microM), and prostaglandin E2 (1 microM) have an inhibitory effect on thrombin (0.3 U/mL)-induced induced proliferation. Furthermore, the cAMP antagonist, 8-bromoadenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (300 microM) significantly reduced the inhibitory effect of salbutamol (10 nM) on thrombin (0.3 U/mL)-induced DNA synthesis. In IBMX (100 microM)-pretreated cells, salbutamol (100 nM) increased intracellular cAMP levels via stimulation of a beta 2-adrenoceptor. Salbutamol (10 microM), at concentrations supramaximally effective for inhibition of mitogenesis, had no effect on thrombin (0.3 U/mL)-induced increases in intracellular calcium levels. Therefore, our results suggest that the previously reported inhibition of mitogen-induced proliferation in human cultured airway smooth muscle cells by the beta 2-adrenoceptor agonist, salbutamol (100 nM), is at least partly due to elevation of intracellular cAMP, while there is no effect of salbutamol on initial mitogen-induced increases in intracellular calcium.

Adrenergic beta-Antagonists↗
PubMed1995

MCF-7 human mammary adenocarcinoma cell death in vitro in response to hormone-withdrawal and DNA damage.

Anti-oestrogens exert a tumoristatic effect on estrogen-receptor-positive breast carcinomas in vivo. At a cellular level this may reflect inhibition of cell proliferation and/or cell death counterbalanced by continued proliferation of a cell subpopulation. We evaluated the MCF-7 human mammary adenocarcinoma cell line as an in vitro model to study the effects of the novel oestrogen antagonist ICI 182,720 on cell population dynamics (cell gain vs. cell loss). After oestrogen-withdrawal monolayer cell number declined over 10 days, accompanied by cell detachment. This decrease in viable cell number was elevated 2-fold by ICI 182,780. Detached cells exhibited DNA fragments of 50 and 300 kbp, typical of apoptotic cells. However, internucleosomal cleavage to 180 bp integer fragments was not seen, and these detached cells exhibited a morphology which was not consistent with apoptosis. The remaining attached monolayer cells were morphologically viable (> 99%) with regard to both nuclear morphology and plasma membrane integrity. There was no difference in cell cycle phase distribution between oestrogen-withdrawn and ICI 182,780-treated cells; both induced accumulation in G1 phase. MCF-7 cells were also exposed to a variety of DNA damaging agents known to induce apoptosis in other cell types. We could demonstrate only limited induction of morphologically recognisable apoptosis in MCF-7 cells treated with methyl methanesulphonate. Our results add to the controversy surrounding the ability of the MCF-7 cell line to undergo apoptosis in vitro in response to anti-oestrogen therapies.

Adenocarcinoma↗
PubMed1995

Issues in protection from galactic cosmic rays.

Radiation risks to astronauts depend on the microscopic fluctuations of energy absorption events in specific tissues. These fluctuations depend not only on the space environment but also on the modifications of that environment by the shielding provided by structures surrounding the astronauts and the attenuation characteristics of the astronaut's body. The effects of attenuation within the shield and body depends on the tissue biological response to these microscopic fluctuations. In the absence of an accepted method for estimating astronaut risk, we examined the attenuation characteristics using conventional linear energy transfer (LET)-dependent quality factors (as one means of representing relative biological effectiveness, RBE) and a track-structure repair model to fit cell transformation (and inactivation) data in the C3H10 T1/2 mouse cell system obtained for various ion beams. Although the usual aluminum spacecraft shield is effective in reducing dose equivalent with increasing shield thickness, cell transformation rates are increased for thin aluminum shields. Clearly, the exact nature of the biological response to LET and track width is critical to evaluation of biological protection factors provided by a shield design. A significant fraction of biological injury results from the LET region above 100 keV/mu m. Uncertainty in nuclear cross-sections results in a factor of 2-3 in the transmitted LET spectrum beyond depths of 15 g/cm2, but even greater uncertainty is due to the combined effects of uncertainty in biological response and nuclear parameters. Clearly, these uncertainties must be reduced before the shield design can be finalised.

Animals↗
PubMed1995

Initiation-promotion model of tumor prevalence in mice from space radiation exposures.

Exposures in space consist of low-level background components from galactic cosmic rays (GCR), occasional intense-energetic solar-particle events, periodic passes through geomagnetic-trapped radiation, and exposure from possible onboard nuclear-propulsion engines. Risk models for astronaut exposure from such diverse components and modalities must be developed to assure adequate protection in future NASA missions. The low-level background exposures (GCR), including relativistic heavy ions (HZE), will be the ultimate limiting factor for astronaut career exposure. We consider herein a two-mutation, initiation-promotion, radiation-carcinogenesis model in mice in which the initiation stage is represented by a linear kinetics model of cellular repair/misrepair, including the track-structure model for heavy ion action cross-sections. The model is validated by comparison with the harderian gland tumor experiments of Alpen et al. for various ion beams. We apply the initiation-promotion model to exposures from galactic cosmic rays, using models of the cosmic-ray environment and heavy ion transport, and consider the effects of the age of the mice prior to and after the exposure and of the length of time in space on predictions of relative risk. Our results indicate that biophysical models of age-dependent radiation hazard will provide a better understanding of GCR risk than models that rely strictly on estimates of the initial slopes of these radiations.

Animals↗
PubMed1995

Theoretical nuclear database for high-energy, heavy-ion (HZE) transport.

Theoretical methods for estimating high-energy, heavy-ion (HZE) particle absorption and fragmentation cross-sections are described and compared with available experimental data. Differences between theory and experiment range from several percent for absorption cross-sections up to about 25%-50% for fragmentation cross-sections.

Cosmic Radiation↗
PubMed1995

A Green's function method for heavy ion beam transport.

The use of Green's function has played a fundamental role in transport calculations for high-charge high-energy (HZE) ions. Two recent developments have greatly advanced the practical aspects of implementation of these methods. The first was the formulation of a closed-form solution as a multiple fragmentation perturbation series. The second was the effective summation of the closed-form solution through nonperturbative techniques. The nonperturbative methods have been recently extended to an inhomogeneous, two-layer transport media to simulate the lead scattering foil present in the Lawrence Berkeley Laboratories (LBL) biomedical beam line used for cancer therapy. Such inhomogeneous codes are necessary for astronaut shielding in space. The transport codes utilize the Langley Research Center atomic and nuclear database. Transport code and database evaluation are performed by comparison with experiments performed at the LBL Bevalac facility using 670 A MeV 20Ne and 600 A MeV 56Fe ion beams. The comparison with a time-of-flight and delta E detector measurement for the 20Ne beam and the plastic nuclear track detectors for 56Fe show agreement up to 35%-40% in water and aluminium targets, respectively.

Aluminum↗
PubMed1995

HLA and ethnic associations among systemic sclerosis patients with anticentromere antibodies.

SSc with ACAs is characterized by limited cutaneous involvement and, in most patients, a mild protracted course. We have studied 104 SSc patients, 47 with ACAs and 57 who were negative for both ACAs and anti-topo I antibodies, for HLA-DR and -DQ associations using DNA typing techniques. Normal controls consisted of 181 healthy individuals. A significant association was observed in the ACA-positive patients with DQB1-0501 (p = 0.001, RR 2.6). There was also a significant decrease in the frequency of DQB1-0201 (p = 0.01, RR 0.33). In addition, the ACA-positive SSc patients were significantly different ethnically from both the other SSc patients and the normal controls (p = 0.004). When patients were stratified according to their ethnic origin and the analysis of HLA associations was repeated, the HLA associations persisted. These results strongly suggest that the development of SSc with ACAs is associated with particular DQB1 alleles, and also that ethnic origin plays a role in disease susceptibility.

Adult↗
PubMed1995

Measurements of the secondary particle energy spectra in the Space Shuttle.

Measurements of the energy spectra of secondary particles produced by galactic cosmic rays and trapped protons due to the nuclear interactions of these particles with the Shuttle shielding provide a powerful tool for validating radiation transport codes. A code validated in this way can be used to better estimate the dose and dose equivalent to body organs, measurements that cannot be made directly. The principal cause of single event upsets in electronic devices in the region of the South Atlantic Anomaly is secondary particles, and even in the region of galactic cosmic radiation a significant fraction is produced by secondary particles. In this paper, we describe the first direct measurements of the energy spectra of secondary protons, deuterons, tritons, 3He and 4He produced by galactic cosmic rays inside the Space Shuttle using a charged particle spectrometer. A comparison of these spectra with radiation transport code HZETRN showed reasonably good agreement for secondary protons. However, the code seriously underestimated the flux of all other light ions. The code has been modified to include pick-up and knock-on processes. The modified code leads to good agreement for deuterons and 3He but not for other light ions. This revised code leads to about 10% higher dose equivalent than the original code under moderate shielding, if we assume that higher charge ion fluxes are correctly predicted by the model.

Atlantic Ocean↗
PubMed1995

Evaluation of the combination of vinblastine and quinidine in patients with metastatic renal cell carcinoma. A phase I study.

Quinidine is known to inhibit p-glycoprotein and enhance the activity of vinblastine against cultured renal carcinoma cells. We have combined quinidine and vinblastine in a Phase I trial in patients with metastatic renal cell carcinoma. Twenty-three patients were entered. Prior treatment included nephrectomy (15 patients), radiation (1 patient) and interferons (8 patients). Cohorts of patients were treated at one of three quinidine dose levels (100, 200, and 400 mg); one patient received 300 mg. Quinidine was given orally 4 times daily starting 3 days prior to the first dose of vinblastine of 5 mg/m2 intravenously given once a week. Hematologic parameters, EKG, and quinidine levels were monitored weekly. Mean quinidine levels in each dose tier were 1.58, 2.59, and 4.24 micrograms/ml, respectively. The dose-limiting toxicity was leukopenia, which necessitated dose interruptions in 16 patients. The mean nadir WBC count (x 10(9)/L) was 3.47, 2.3, and 1.73 in each dose tier, respectively. Corresponding values for the mean maximum decrease in WBC count from baseline were 3.85, 5.86, and 6.53, respectively. There was a trend for leukopenia to become more severe with increasing doses of quinidine. Other toxicities included mild nausea and vomiting in all patients, and hypotension and paralytic ileus in one patient each. No cardiac toxicity was observed. One patient had a complete remission and 4 patients had stable disease. We conclude that quinidine and vinblastine may be administered together safely in a clinical setting, with leukopenia being dose-limiting. Further studies are needed to determine any therapeutic advantage over vinblastine alone.

Adult↗
PubMed1995

Issues in space radiation protection: galactic cosmic rays.

When shielding from cosmic heavy ions, one is faced with limited knowledge about the physical properties and biological responses of these radiations. Herein, the current status of space shielding technology and its impact on radiation health is discussed in terms of conventional protection practice and a test biological response model. The impact of biological response on optimum materials selection for cosmic ray shielding is presented in terms of the transmission characteristics of the shield material. Although liquid hydrogen is an optimum shield material, evaluation of the effectiveness of polymeric structural materials must await improvement in our knowledge of both the biological response and the nuclear processes.

Astronauts↗
PubMed1995

Calculation of dose, dose equivalent, and relative biological effectiveness for high charge and energy ion beams.

The Green's function for the transport of ions of high charge and energy is utilized with a nuclear fragmentation database to evaluate dose, dose equivalent, and RBE for C3H10T1/2 cell survival and neoplastic transformation as a function of depth in soft tissue. Such evaluations are useful to estimates of biological risk for high altitude aircraft, space operations, accelerator operations, and biomedical applications.

Aircraft↗
PubMed1995

Variations in astronaut radiation exposure due to anisotropic shield distribution.

The dose incurred in an environment generated by extraterrestrial space radiations within an anisotropic shield distribution depends on the orientation of the astronaut's body relative to the shield geometry. The fluctuations in exposure of specific organ sites due to astronaut re-orientation are found to be a factor of 2 or more in a typical space habitation module and typical space radiations. An approximation function is found that overestimates astronaut exposure in most cases studied and is recommended as a shield design guide for future deep space missions.

Astronauts↗
PubMed1995

Effects of target fragmentation on evaluation of LET spectra from space radiation in low-earth orbit (LEO) environment: impact on SEU predictions.

Recent improvements in the radiation transport code HZETRN/BRYNTRN and galactic cosmic ray environmental model have provided an opportunity to investigate the effects of target fragmentation on estimates of single event upset (SEU) rates for spacecraft memory devices. Since target fragments are mostly of very low energy, an SEU prediction model has been derived in terms of particle energy rather than linear energy transfer (LET) to account for nonlinear relationship between range and energy. Predictions are made for SEU rates observed on two Shuttle flights, each at low and high inclination orbit. Corrections due to track structure effects are made for both high energy ions with track structure larger than device sensitive volume and for low energy ions with dense track where charge recombination is important. Results indicate contributions from target fragments are relatively important at large shield depths (or any thick structure material) and at low inclination orbit. Consequently, a more consistent set of predictions for upset rates observed in these two flights is reached when compared to an earlier analysis with CREME model. It is also observed that the errors produced by assuming linear relationship in range and energy in the earlier analysis have fortuitously canceled out the errors for not considering target fragmentation and track structure effects.

Aluminum↗
PubMed1995

Tumor necrosis factor alpha modulates mitogenic responses of human cultured airway smooth muscle.

Airway wall remodeling, including hyperplasia of airway smooth muscle, is regarded as an important contributor to airway hyperresponsiveness in asthmatic patients. The effects of the proinflammatory cytokine, tumor necrosis factor alpha (TNF alpha) on the mitogenic responses of human cultured airway smooth muscle have been investigated. Lower concentrations of TNF alpha (0.3 to 30 pM) had a small, delayed (48-h incubation), stimulatory effect on DNA synthesis that was blocked by dexamethasone (1 microM), aspirin (100 microM), or primaquine (30 microM) pretreatment, indicating that this effect was secondary to the release of cyclooxygenase products. TNF alpha (300 pM; 24- to 48-h incubation) alone had no effect on cell number or DNA or protein synthesis, but markedly reduced the stimulatory effects of thrombin (0.3 U/ml). TNF alpha (300 pM) also inhibited mitogenic responses to fetal calf serum (10%), epidermal growth factor (300 pM), and the thromboxane A2 mimetic U46619 (100 nM), indicating a nonselective effect. The inhibitory effects of TNF alpha (300 pM) were not blocked by pretreating the cells with the cyclooxygenase inhibitor aspirin (100 microM), the 5-lipoxygenase inhibitor CGS 8515 (3 microM), or the nitric oxide synthase inhibitor nitro-iminoethyl-L-ornithine (100 microM), suggesting that neither arachidonic acid metabolites nor nitric oxide were mediators of the inhibitory effect. The phospholipase A2 inhibitor primaquine (30 microM) had no effect on the inhibitory responses to TNF alpha, whereas the anti-inflammatory steroid dexamethasone (1 microM) prevented TNF alpha inhibition of mitogenic responses. Thus, concentrations of TNF alpha, within the range detected in bronchoalveolar lavage fluid from asthmatics, suppress mitogenic responses by a mechanism that is sensitive to inhibition by anti-inflammatory steroids, but does not appear to involve established targets for modulation by steroids, including arachidonic acid metabolism or induction of nitric oxide synthase.

Aged↗