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Biomedical subjects

D W Pearson

Publications and source records attributed to D W Pearson.

At least 19 recordsLinked to original sources
PubMed2002

The effect of spectra on calibration and measurement with mammographic ionization chambers.

Mammographic imaging uses x-ray tubes with molybdenum, rhodium, or tungsten anodes with the produced bremsstrahlung filtered by thin sheets of molybdenum, rhodium, or aluminum. The National Institute of Standards and Technology, the Accredited Dosimetry Calibration Laboratories, and several manufacturers offer calibrations of mammography ionization chambers with reference x-ray beams with different radiation qualities in the range 23-40 kVp. The energy response of ten commercially available chambers was determined for these reference radiation qualities using the Attix variable-length free-air chamber. The evaluated chambers are designed with thin entrance windows of varying thickness and composition. The chambers show variation in their air kerma response as a function of beam radiation quality. This response with beam radiation quality may affect the measurement of clinical beam half value layer (HVL) and the determination of the mean glandular dose. The combined effect of the chamber's energy dependence and HVL measurement affects the mean glandular dose calculation resulting in differences ranging from -1.8% to +2.5%.

Calibration↗
PubMed2001

Measurements and Monte Carlo calculations to determine the absolute detector response of radiochromic film for brachytherapy dosimetry.

GafChromic (MD-55-2) radiochromic film has become increasingly popular for medical applications and has proven to be useful for brachytherapy dosimetry. To measure the absolute dose near a brachytherapy source, the response of the proposed detector in the measurement conditions relative to the response of the detector in calibration conditions must be known. MD-55-2 radiochromic film has been exposed in four different photon beams, a 30 and 40 kVp tungsten anode x-ray beam, a 75 kVp orthovoltage therapy beam, and a 60Co teletherapy beam to measure the relative detector response. These measurements were combined with coupled photon/electron Monte Carlo transport calculations to determine the absolute detector response. The Los Alamos National Laboratory Monte Carlo transport code MCNP4B2 was used. The measured relative response of this batch of MD-55-2 film varies from 8.79 mOD/Gy, measured for the 60Co beam, by as much as 42% for the low-energy x-ray beams. However, the absolute detector response varies from 4.32 mOD/Gy for the 60Co beam by, at most, only 6.3%. In this work we demonstrate that the absolute detector response of MD-55-2 radiochromic film is a constant and independent of beam quality. Further, this work shows that MCNP4B2 accurately simulates the energy response and geometry artifacts of the radiochromic film.

Biophysical Phenomena↗
PubMed1999

Registration using tomographic projection files.

An algorithm has been developed and experimentally verified for tomographic registration--a patient positioning method using internal anatomy and standard external fiducial marks. This algorithm improves patient set-up and verification to an accuracy sufficient for tomotherapy. By implementation of this technique, the time-consuming reconstruction process is avoided. Instead, offsets in the x, y and z directions are determined directly from sinogram data by an algorithm that utilizes cross-correlations and Fourier transforms. To verify the efficiency and stability of the algorithm, data were collected on the University of Wisconsin's dedicated tomotherapy research workbench. The experiment indicates offset statistical errors of less than +/-0.8 mm for offsets up to 30 mm. With standard clinical techniques, initial patient offsets are expected to be less than 5 mm, so the 30 mm limitation is of no consequence. The angular resolution for the direction of patient translation is within the +/-2 degrees needed for tomotherapy.

Algorithms↗
PubMed1999

Dependence of scatter on atomic number for x rays from tungsten and molybdenum anodes in the mammographic energy range.

A study was done to determine the relative amounts of scatter for the following materials with atomic numbers ranging from Z=6 to Z=82: C, Al, Ti, Fe, Cu, Zn, Zr, Y, Mo, Ta, and Pb. Measurements were performed for each material on two constant potential x-ray units--one fitted with a molybdenum (Mo) anode-Mo filter and the other with a tungsten (W) anode-aluminum (Al) filter (medium filtration) at 30 kVp. Theoretical calculations were also performed for each anode to explain the scatter behavior and to aid in predicting the behavior for materials where measurements were not made. There was good agreement between the theoretical calculations and the experimental data.

Biophysics↗
PubMed1998

A double mirror W/C multilayer monochromator for radiation biology applications.

A double-mirror multilayer monochromator was developed for the purpose of irradiating live cell cultures at the Synchrotron Radiation Center, University of Wisconsin-Madison. The monochromator is designed for the soft x-ray region with photon energies between 270 and 2400 eV. Multilayer mirrors with 55 bilayers of W/C and a bilayer spacing of d = 3.0 nm are sputter deposited on Si substrates. By proper masking of the sputtering sources, variation in the bilayer spacing over the area of the mirror is minimized. The uniformity of the bilayer spacing was measured to be delta d/d < 1%, over the 75 mm x 25 mm area of the mirrors. The reflectivity was measured as a function of energy to determine the integrated reflectivity and evaluate the contribution of the specular reflection and higher orders to the monochromatic beam. The use of suitable filters with a Si(Li) detector allows determination of the spectral output of the monochromator. The output power of the monochromator between 270 and 2400 eV is measured. The resolution of the monochromator is delta lambda/lambda = 0.04. Applications of the monochromator to radiation biology are discussed.

Cells, Cultured↗
PubMed1998

Synchroton-produced ultrasoft X rays: equivalent cell survival at the isoattenuating energies 273 eV and 860 eV.

In this paper we report on survival of Chinese hamster V79 and mouse C3H 10T1/2 cells after irradiation with synchrotron-produced 273 eV and 860 eV ultrasoft X rays. These two energies, which are available by multilayer monochromatization of the synchrotron output spectrum, exhibit equal attenuation within living cells. Such an isoattenuating energy pair allows the direct examination of how biological effectiveness varies with the energy of the ultrasoft X rays. In comparing survival results, we find similar biological effectiveness of these two energies for both the C3H 10T1/2 and the V79 cells. These results are not consistent with previous findings of increasing RBE with decreasing ultrasoft X-ray energies. In addition, after correcting for mean nuclear dose based on measurements of cell thickness obtained with confocal microscopy, we find no significant differences in survival between the two ultrasoft X-ray energies and 250 kVp X rays. These results suggest that RBE does not increase with decreasing energy of ultrasoft X rays between 860 eV and 273 eV. The possible impact of our results on past results for ultrasoft X rays is discussed.

Animals↗
PubMed1997

Calreticulin biosynthesis and processing in human myeloid cells: demonstration of signal peptide cleavage and N-glycosylation.

Calreticulin is a soluble endoplasmic reticulum protein comprising the major storage reservoir for inositol trisphosphate-releasable calcium. Although its highly conserved primary structure and a wide range of functions have been well described, less attention has been paid to its biosynthesis, particularly in human tissues. We report analyses of synthesis, proteolytic processing and glycosylation of human calreticulin. In both HL-60 and PLB-985 myeloid cell lines calreticulin was immunoprecipitated as a single 60-kD species without evidence of precursor forms. However, in vitro cell-free synthesis produced a 62-kD primary translation product, which in the presence of microsomal membranes, was processed by cotranslational signal peptide cleavage to a 60-kD species that comigrated with mature calreticulin produced in myeloid cells. Neither tunicamycin treatment of the cells nor endoglycosidase digestion of calreticulin resulted in any forms other than the 60-kD protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, suggesting that the potential site for N-glycosylation at asparagine-327 was unmodified. However, oxidative derivatization of carbohydrate components with digoxigenin showed that human calreticulin produced in either HL-60 cells or Sf9 insect cells is glycosylated, indicating that glycosylated and nonglycosylated human calreticulin have indistinguishable electrophoretic mobilities. Direct measurement by phenol-H2SO4 confirmed the presence of carbohydrate on recombinant human calreticulin. These data show that human myeloid calreticulin undergoes cotranslational signal peptide cleavage and posttranslational N-linked glycosylation. Although glycosylation of calreticulin has been shown in rat liver and bovine liver and brain, it has been reported to be lacking in other tissues including human lymphocytes.

Animals↗
PubMed1997

Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration.

Diabetic retinal neovascularisation is considered to be a consequence of retinal ischaemia caused by capillary occlusion. Capillary occlusion is the result of microvascular thrombi in which erythrocytes, platelets and leucocytes each may play a role. We investigated the role of leucocytes in this process and the subsequent angiogenic response. We studied the serum levels of the soluble leucocyte adhesion molecules soluble E-Selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in the serum of 93 patients with insulin-dependent diabetes (IDDM) and varying degrees of retinopathy and 47 healthy age and sex matched control subjects. We also measured the ability of serum to stimulate retinal capillary endothelial cell migration using an assay of angiogenesis in vitro. Soluble E-Selectin and sVCAM-1 levels were raised in all patients with IDDM (p < 0.001; p < 0.001) particularly those with retinopathy (p < 0.001; p < 0.001). Soluble E-Selectin levels were highest in the patients with severe non-proliferative diabetic retinopathy (p < 0.001) and sVCAM-1 levels were highest in patients with proliferative diabetic retinopathy (p < 0.01). In contrast soluble ICAM-1 levels were the same in patients and control subjects (p > 0.05). Soluble E-Selectin levels in diabetic patients were correlated with the level of glycated haemoglobin (p < 0.05). Retinal endothelial cell migration-inducing (ECMI) activity was increased in patients with IDDM (p < 0.01) in particular in those with retinopathy (p < 0.01). Furthermore, in vitro ECMI activity could be blocked by antibodies to sVCAM-1 and sE-Selectin. These data point to a functional role for leucocyte adhesion in the microvasculopathy of diabetic retinopathy and may have implications for the induction of retinal angiogenesis.

Adult↗
PubMed1997

Comparison of exposure standards in the mammography x-ray region.

Direct comparisons of the National Institute of Standards and Technology's (NIST) Ritz 20 kV to 100 kV standard free-air ionization chamber and a portable variable-length free-air ionization chamber designed by the University of Wisconsin-Madison Accredited Dosimetry Calibration Laboratory (UW-ADCL) were made on NISTs low-energy tungsten x-ray range. As a result of this direct comparison, NIST has established a UW-ADCL designed chamber, the Attix chamber, as the national standard chamber for the mammography energy x-ray range. The Ritz standard chamber and the Attix standard chamber have been extensively compared using the new molybdenum and rhodium beam qualities. The results indicate that exposure measurements in the mammography energy x-ray region with the two free-air chambers can be made with a discrepancy of less than 0.35%.

Evaluation Studies as Topic↗
PubMed1994

Human inositol 1,4,5-trisphosphate type-1 receptor, InsP3R1: structure, function, regulation of expression and chromosomal localization.

We have isolated cDNA clones encoding an inositol 1,4,5-trisphosphate receptor type 1 (InsP3R1) from human uteri and a leukaemic cell line, HL-60. Northern-blot analysis showed that approx. 10 kb of InsP3R1 mRNA is expressed in human uteri, oviducts and HL-60 cells. The predicted amino acid sequence of human InsP3R1 (2695 amino acids) has 99% identity with that of the mouse SI-/SII- splicing counterpart. Western-blot analysis with anti-(mouse InsP3R1) antibodies showed that InsP3R1 protein of human uteri and oviducts of approx 220 kDa is immunostained. Northern-blot analysis of HL-60 cell differentiation along the neutrophilic lineage induced by retinoic acid or dimethylsulphoxide showed an accompanying enhanced expression of InsP3R1 mRNA. Immunohistochemical analysis of the cerebella of spinocerebellar degeneration patients showed a variable loss of Purkinje cells with an altered pattern of immunostaining. The InsP3R1 gene (Insp3r1) was localized to the 3P25-26 region of human chromosome 3. The data presented here clearly show that InsP3R1 exists widely in human tissues and may play critical roles in various kinds of cellular functions.

Adult↗
PubMed1994

Evidence for a readily dissociable complex of p47phox and p67phox in cytosol of unstimulated human neutrophils.

We explored the association between two cytosolic components of the phagocyte respiratory burst oxidase, p47phox and p67phox. Both of these proteins bound to immobilized GTP or 2',5'-ADP, but not to GDP or ATP. Similarly, triazine dye-ligand chromatography demonstrated coisolation of p47phox and p67phox. Binding of p67phox to GTP was less avid than that of p47phox. Each of the proteins in whole neutrophil cytosol bound separately to GTP in the absence of the other, whereas studies with recombinant proteins showed binding of p47phox but not p67phox. These data suggest that p47phox and p67phox exist as a complex that very likely involves at least one additional cytosolic protein. Sequential precipitation in graded concentrations of ammonium sulfate demonstrated similar profiles for p47phox and p67phox. Charge-based separations using either an anion or cation exchange resin resulted in coelution of the two cytosolic oxidase components, in spite of their widely differing charges as shown by separate analysis of the recombinant proteins. Moreover, preparative isoelectric focusing showed that a portion of the p47phox and p67phox in cytosol coisolated at a pI (7.3-8.3) midway between those of the separate proteins. Despite this, each protein sedimented independently in sucrose density gradients. The data indicate that the complex of p47phox and p67phox was dissociated by increased temperature, high osmolarity, or prolonged incubation. We suggest that under the physiologic conditions in the cytosol of intact phagocytes p47phox, p67phox and probably other proteins exist as a macromolecular complex, the function of which may be to permit en bloc translocation of oxidase components to the plasma membrane.

Ammonium Sulfate↗
PubMed1994

Maternal glucose response to a standardized test meal throughout pregnancy and postnatally.

OBJECTIVE: Our purpose was to determine the maternal blood glucose response to food throughout pregnancy. STUDY DESIGN: Forty-five normal, healthy primiparous women with singleton pregnancies were studied longitudinally throughout pregnancy. Blood glucose levels were determined at each stage of pregnancy after a standardized test meal. RESULTS: Fasting plasma glucose decreased throughout gestation and rose again significantly post partum. Glucose values at 30, 60, 90, and 120 minutes after a standardized test meal were similar at all gestational ages studied. CONCLUSIONS: Plasma glucose levels after a physiologic challenge with food do not alter with advancing gestation. This has implications both for the management of insulin-dependent diabetes during pregnancy and for the diagnosis of gestational diabetes.

Adult↗
PubMed1994

Response of thermoluminescent lithium fluoride (TLD-100) to photon beams of 275, 400, 500, 600, 730, 900, 1200, 1500, and 2500 eV.

LiF:Mg,Ti (TLD-100) extruded ribbons and cleaved crystals were exposed to monoenergetic photons of 275-2550 eV energy to determine their potential usefulness as radiation dosimeters for radiobiology experiments at these energies. The radiation source was synchrotron radiation from the 1 GeV electron storage ring, Aladdin. The authors report TLD response and glow curves for He- and air-annealed dosimeters. The undesirable effects of air annealing increase with decreasing photon penetration in the dosimeter. Under certain experimental conditions, UV radiation produced anomalous bleaching of high-temperature traps. The crystals and the chips presented a supralinear response, Supralinearity factors were determined to be of the order of 1.5 for crystals, and 1.7 for the chips. The authors' results indicate that TLDs are a reliable means to monitor the total energy deposited in irradiated cells and are now used routinely for radiobiology cell irradiations.

Biophysical Phenomena↗
PubMed1992

The ranges of insulin response and glucose tolerance in lean, normal, and obese women during pregnancy.

OBJECTIVE: We characterized insulin secretion and glucose disposal in a large unselected group of women, encompassing the full spectrum of glucose tolerance in pregnancy, and related the findings to maternal obesity. STUDY DESIGN: Intravenous glucose tolerance and first-phase insulin response were measured at about 32 weeks' gestation in 690 unselected pregnancies. The women were designated as "lean," "normal," or "obese" on weight-for-height criteria. RESULTS: The distribution of insulin response was bimodal, but there was no corresponding dichotomy in maternal glucose disposal rate. Insulin response was greatest and glucose disposal rate slowest in obese women. In general, "poor" glucose tolerance was associated with relatively low insulin output. It was not possible to identify any cluster of women, obese or otherwise, in whom poor glucose tolerance was specifically associated with an unusually high insulin response. CONCLUSION: The data indicate that the distribution of glucose tolerance in pregnancy is a continuum. Glucose intolerance represents one end of that spectrum and is attributable to insufficient insulin secretion. This relative insufficiency is most frequent with maternal obesity.

Blood Glucose↗
PubMed1991

Synchrotron-produced ultrasoft X-rays: a tool for testing biophysical models of radiation action.

Ultrasoft X-rays are useful for mechanistic studies of ionizing radiation damage in living cells due to the localized nature of their energy depositions. To date radiobiology experiments in this energy region have relied on characteristic X-rays (mainly Alk and Ck) from X-ray tubes. However, limitations in the photon intensity and the available energies from X-ray tube sources prevent a definitive characterization of the relationship between photon energy and biological damage. Synchrotron radiation has the potential to avoid these limitations, since it produces X-rays with high intensity over a continuous spectrum. We have established a synchrotron-based system for radiation biology studies using the ES-0 exposure station of the Center for X-ray Lithography at the University of Wisconsin Synchrotron Radiation Center storage ring, Aladdin. A characterization of the system including spectral and intensity properties of the photon beam is presented. The first mammalian cell survival curve for synchrotron-produced ultrasoft X-rays was generated and is presented. Cell survival curves of C3H/10T 1/2 cells using synchrotron radiation of 1.48 keV agree with previous data using Alk X-rays (1.49 keV). An RBE of 1.47 +/- 0.30 at the 10% survival level was measured with reference to 250 kVp X-rays.

Animals↗
PubMed1991

Neutrophil nicotinamide adenine dinucleotide phosphate oxidase assembly. Translocation of p47-phox and p67-phox requires interaction between p47-phox and cytochrome b558.

Two of the cytosolic NADPH oxidase components, p47-phox and p67-phox, translocate to the plasma membrane in normal neutrophils stimulated with phorbol myristate acetate (PMA). We have now studied the translocation process in neutrophils of patients with chronic granulomatous disease (CGD), an inherited syndrome in which the oxidase system fails to produce superoxide due to lesions affecting any one of its four known components: the gp91-phox and p22-phox subunits of cytochrome b558 (the membrane-bound terminal electron transporter of the oxidase), p47-phox, and p67-phox. In contrast to normal cells, neither p47-phox nor p67-phox translocated to the membrane in PMA-stimulated CGD neutrophils which lack cytochrome b558. In one patient with a rare X-linked form of CGD caused by a Pro----His substitution in gp91-phox, but whose neutrophils have normal levels of this mutant cytochrome b558, translocation was normal. In two patients with p47-phox deficiency, p67-phox failed to translocate, whereas p47-phox was detected in the particulate fraction of PMA-stimulated neutrophils from two patients deficient in p67-phox. Our data suggest that cytochrome b558 or a closely linked factor provides an essential membrane docking site for the cytosolic oxidase components and that it is p47-phox that mediates the assembly of these components on the membrane.

Biological Transport↗