bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of electron contamination in megavoltage photon beams
Authors: Medina Antonio Lopez , Teijeiro Antonio , Garcia Juan , Esperon Jorge , Terron J. Antonio , Ruiz Diego P. , Carrion Maria C.
Published: May 2005

The purpose of the present study is to characterize electron contamination in photon beams in different clinical situations. Variations with field size, beam modifier (tray, shaping block) and source–surface distance (SSD) were studied. Percentage depth dose measurements with and without a purging magnet and replacing the air by helium were performed to identify the two electron sources that are clearly differentiated: air and treatment head. Previous analytical methods were used to fit the measured data, exploring the validity of these models. Electrons generated in the treatment head are more energetic and more important for larger field sizes, shorter SSD, and greater depths. This difference is much more noticeable for the beam than for the beam. If a tray is used as beam modifier, electron contamination increases, but the energy of these electrons is similar to that of electrons coming from the treatment head. Electron contamination could be fitted to a modified exponential curve. For machine modeling in a treatment planning system, setting SSD at for input data could reduce errors for most isocentric treatments, because they will be delivered for SSD ranging from . For very small field sizes, air‐generated electrons must be considered independently, because of their different energetic spectrum and dosimetric influence.
Time delay measurement for linac based treatment delivery in synchronized respiratory gating radiotherapy
Authors: Jin Jian‐Yue , Yin Fang‐Fang
Published: May 2005

A time delay in a respiratory gating system could cause an unexpected phase mismatch for synchronized gating radiotherapy. This study presents a method of identifying and measuring the time delay in a gating system. Various port films were taken for a motion phantom at different gating window levels with a very narrow window size. The time delay for the gating system was determined by comparing the motion curve (the position of a moving object versus the gating time) measured in the port films to the motion curve determined by the video cameras. The measured time delay for a linac‐based gating system was . This time delay could induce target missing if it was not properly taken into account for the synchronized gating radiotherapy. Measurement/verification of the time delay should be considered as an important part of the accepting/commissioning test before the clinical use of the gating system.
The helical tomotherapy thread effect
Authors: Kissick M. W. , Fenwick J. , James J. A. , Jeraj R. , Kapatoes J. M. , Keller H. , Mackie T. R. , Olivera G. , Soisson E. T.
Published: May 2005

Inherent to helical tomotherapy is a dose variation pattern that manifests as a “ripple” (peak‐to‐trough relative to the average). This ripple is the result of helical beam junctioning, completely unique to helical tomotherapy. Pitch is defined as in helical CT, the couch travel distance for a complete gantry rotation relative to the axial beam width at the axis of rotation. Without scattering or beam divergence, an analytical posing of the problem as a simple integral predicts minima near a pitch of where is an integer. A convolution‐superposition dose calculator (TomoTherapy, Inc.) included all the physics needed to explore the ripple magnitude versus pitch and beam width. The results of the dose calculator and some benchmark measurements demonstrate that the ripple has sharp minima near . The 0.86 factor is empirical and caused by a beam junctioning of the off‐axis dose profiles which differ from the axial profiles as well as a long scatter tail of the profiles at depth. For very strong intensity modulation, the 0.86 factor may vary. The authors propose choosing particular minima pitches or using a second delivery that starts 180 deg off‐phase from the first to reduce these ripples: “Double threading.” For current typical pitches and beam widths, however, this effect is small and not clinically important for most situations. Certain extremely large field or high pitch cases, however, may benefit from mitigation of this effect.
Optimized source selection for intracavitary low dose rate brachytherapy
Authors: Nurushev T. , Kim Jinkoo
Published: May 2005

A procedure has been developed for automating optimal selection of sources from an available inventory for the low dose rate brachytherapy, as a replacement for the conventional trial‐and‐error approach. The method of optimized constrained ratios was applied for clinical source selection for intracavitary Cs‐137 implants using Varian BRACHYVISION software as initial interface. However, this method can be easily extended to another system with isodose scaling and shaping capabilities. Our procedure provides optimal source selection results independent of the user experience and in a short amount of time. This method also generates statistics on frequently requested ideal source strengths aiding in ordering of clinically relevant sources
Radiological properties of a wax–gypsum compensator material
Authors: du Plessis F. C. P. , Willemse C. A.
Published: May 2005

In this paper the radiological properties of a compensator material consisting of wax and gypsum is presented. Effective attenuation coefficients (EACs) have been determined from transmission measurements with an ion chamber in a Perspex phantom. Measurements were made at 80 and 100 cm source‐to‐skin distance (SSD) for beam energies of 6, 8, and 15 MV, for field sizes ranging from narrow beam geometries up to , and at measurement depths of maximum dose build‐up, 5 and 10 cm. A parametrization equation could be constructed to predict the EAC values within 4% uncertainty as a function of field size and depth of measurement. The EAC dependence on off‐axis position was also quantified at each beam energy and SSD. It was found that the compensator material reduced the required thickness for compensation by 26% at 8 MV when compared to pure paraffin wax for a field. Relative surface ionization (RSI) measurements have been made to quantify the effect of scattered electrons from the wax–gypsum compensator. Results indicated that for 80 cm SSD the RSI would exceed 50% for fields larger than . At 100 cm SSD the RSI values were below 50% for all field sizes used.
Presampling, algorithm factors, and noise: Considerations for CT in particular and for medical imaging in general
Authors: Kachelrieß Marc , Kalender Willi A.
Published: May 2005

CT scanners acquire noisy data at discrete sample positions. Typically, a convention of how to continue these data from discrete integer positions to the continuous domain must be applied during processing. We study the properties of three typical one‐dimensional spatial domain interpolation algorithms in terms of a cost or quality factor . This figure of merit is a function of spatial resolution, data noise, and dose and is used to optimize detector design. Spatial resolution is defined as either mean square width or as the full width at half maximum of the point spread function (PSF). Our results show that a trapezoidal interpolation algorithm is optimal for the high resolution domain (relative to the detector aperture size ) and should be replaced by a triangular or Gaussian interpolation function for spatial resolutions of about or larger; these result in bell‐shaped PSFs. Assuming such a hybrid algorithm we find a 1.5‐fold increase of —this is equivalent to 50% improved dose usage—when smoothing the data to a spatial resolution of or more compared to a highest resolution reconstruction. Therefore it is advisable to use detectors of one‐third of the size of the desired spatial resolution and to compensate for the 1.5‐fold increase in by reducing dose by 33%. Under the presence of moderately sized septa (e.g., 10% of the spatial resolution element size) the benefit of optimizing still lies in the order of 30% improved dose usage; in that case the detector size should be on the order of and a dose reduction of 23% can be achieved. Again, bell‐shaped PSFs show a better tradeoff between noise and resolution for a given dose than rectangular‐shaped PSFs. The general interpretation of our results is that the degree of freedom of choosing the weighting or interpolation function for a given resolution is large for small detectors and small for large detectors. Thus systems with small have a higher potential of optimization compared to systems with large . Similarly, detector binning, which corresponds to replacing by , should be avoided. Note that the figures reported correspond to a one‐dimensional interpolation. Two‐dimensional detectors typically separate and resulting quality factors can be easily obtained by multiplication. Then, is expected to improve by a factor of without septa and by a factor of with septa. This indicates that dose can be reduced by about 56% and about 41%, respectively. Our findings are general and not restricted to CT. They can be readily applied to medical or nonmedical imaging devices and digital detectors and they may also turn out to be useful in other fields.
A Monte Carlo derived TG‐51 equivalent calibration for helical tomotherapy
Authors: Thomas S. D. , Mackenzie M. , Rogers D. W. O. , Fallone B. G.
Published: May 2005

Helical tomotherapy (HT) requires a method of accurately determining the absorbed dose under reference conditions. In the AAPM's TG‐51 external beam dosimetry protocol, the quality conversion factor, , is presented as a function of the photon component of the percentage depth‐dose at 10 cm depth, , measured under the reference conditions of a field size and a source‐to‐surface distance (SSD) of 100 cm. The value of from HT cannot be used for the determination of because the design of the HT does not meet the following TG‐51 reference conditions: (i) the field size and the practical SSD required by TG‐51 are not obtainable and (ii) the absence of the flattening filter changes the beam quality thus affecting some components of . The stopping power ratio is not affected because of its direct relationship to . We derive a relationship for the Exradin A1SL ion chamber converting the measured under HT “reference conditions” of and a field‐size , to the dosimetric equivalent value under for TG‐51 reference conditions for HT. This allows the determination of under the HT reference conditions. The conversion results in changes of 0.1% in the value of for our particular unit. The conversion relationship should also apply to other ion chambers with possible errors on the order of 0.1%.
Dose sculpting with generalized equivalent uniform dose
Authors: Wu Qiuwen , Djajaputra David , Liu Helen H. , Dong Lei , Mohan Radhe , Wu Yan
Published: May 2005

With intensity‐modulated radiotherapy (IMRT), a variety of user‐defined dose distribution can be produced using inverse planning. The generalized equivalent uniform dose (gEUD) has been used in IMRT optimization as an alternative objective function to the conventional dose‐volume‐based criteria. The purpose of this study was to investigate the effectiveness of gEUD optimization to fine tune the dose distributions of IMRT plans. We analyzed the effect of gEUD‐based optimization parameters on plan quality. The objective was to determine whether dose distribution to selected structures could be improved using gEUD optimization without adversely altering the doses delivered to other structures, as in sculpting. We hypothesized that by carefully defining gEUD parameters ( and ) based on the current dose distributions, the optimization system could be instructed to search for alternative solutions in the neighborhood, and we could maintain the dose distributions for structures already satisfactory and improve dose for structures that need enhancement. We started with an already acceptable IMRT plan optimized with any objective function. The dose distribution was analyzed first. For structures that dose should not be changed, a higher value of was used and was set slightly higher/lower than the EUD value at the current dose distribution for critical structures/targets. For structures that needed improvement in dose, a higher to medium value of was used, and was set to the EUD value or slightly lower/higher for the critical structure/target at the current dose distribution. We evaluated this method in one clinical case each of head and neck, lung and prostate cancer. Dose volume histograms, isodose distributions, and relevant tolerance doses for critical structures were used for the assessment. We found that by adjusting gEUD optimization parameters, the dose distribution could be improved with only a few iterations. A larger value of could lead to faster convergence and a medium value of could result in a search in a broader area. Such improvement could also be achieved by optimization based on other criteria, but the gEUD‐based method has the advantage of efficiency and flexibility. Therefore, gEUD‐based optimization can be used as a tool to improve IMRT plans by adjusting the planning parameters, thereby making dose sculpting feasible.
Monte Carlo calculations of the absorbed dose and energy dependence of plastic scintillators
Authors: Beddar A. Sam , Briere Tina Marie , Mourtada Firas A. , Vassiliev Oleg N. , Liu H. Helen , Mohan Radhe
Published: May 2005

Detector systems using plastic scintillators can provide instantaneous measurements with high spatial resolution in many applications including small field and high dose gradient field applications. Energy independence and water equivalence are important dosimetric properties that determine whether a detector will be useful in a clinical setting. Using Monte Carlo simulations, we calculated the energy dependence of plastic scintillators when exposed to photon beams in the radiotherapeutic range. These calculations were performed for a detector comprised of a BC‐400 plastic scintillator surrounded by a polystyrene wall. Our results showed the plastic scintillation detector to be nearly energy independent over a range of energies from . The ratio of the dose absorbed by the scintillator to that absorbed by water was nearly a constant, approximately equal to 0.98 over the entire energy range of interest. These results confirm the water equivalence of the plastic scintillation detector and are in very good agreement with earlier results obtained using Burlin cavity theory.
Accounting for beta‐particle energy loss to cortical bone via paired‐image radiation transport (PIRT)
Authors: Shah Amish P. , Rajon Didier A. , Patton Phillip W. , Jokisch Derek W. , Bolch Wesley E.
Published: May 2005

Current methods of skeletal dose assessment in both medical physics (radionuclide therapy) and health physics (dose reconstruction and risk assessment) rely heavily on a single set of bone and marrow cavity chord‐length distributions in which particle energy deposition is tracked within an infinite extent of trabecular spongiosa, with no allowance for particle escape to cortical bone. In the present study, we introduce a paired‐image radiation transport (PIRT) model which provides a more realistic three‐dimensional (3D) geometry for particle transport in the skeletal site at both microscopic and macroscopic levels of its histology. Ex vivo CT scans were acquired of the pelvis, cranial cap, and individual ribs excised from a male cadaver (BMI of ). For the three skeletal sites, regions of trabecular spongiosa and cortical bone were identified and segmented. Physical sections of interior spongiosa were taken and subjected to microCT imaging. Voxels within the resulting microCT images were then segmented and labeled as regions of bone trabeculae, endosteum, active marrow, and inactive marrow through application of image processing algorithms. The PIRT methodology was then implemented within the EGSNRC radiation transport code whereby electrons of various initial energies are simultaneously tracked within both the ex vivo CT macroimage and the CT microimage of the skeletal site. At initial electron energies greater than , a divergence in absorbed fractions to active marrow are noted between PIRT model simulations and those estimated under existing techniques of infinite spongiosa transport. Calculations of radionuclide values under both methodologies imply that current chord‐based models may overestimate the absorbed dose to active bone marrow in these skeletal sites by 0% to 27% for low‐energy beta emitters (, , and ), by to 49% for intermediate‐energy beta emitters (, , and ), and by to 76% for high‐energy beta emitters (, , and ). The PIRT methodology allows for detailed modeling of the 3D macrostructure of individual marrow‐containing bones within the skeleton thus permitting improved estimates of absorbed fractions and radionuclide values for intermediate‐to‐high energy beta emitters.
Generalized DQE analysis of radiographic and dual‐energy imaging using flat‐panel detectors
Authors: Richard S. , Siewerdsen J. H. , Jaffray D. A. , Moseley D. J. , Bakhtiar B.
Published: May 2005

Analysis of detective quantum efficiency (DQE) is an important component of the investigation of imaging performance for flat‐panel detectors (FPDs). Conventional descriptions of DQE are limited, however, in that they take no account of anatomical noise (i.e., image fluctuations caused by overlying anatomy), even though such noise can be the most significant limitation to detectability, often outweighing quantum or electronic noise. We incorporate anatomical noise in experimental and theoretical descriptions of the “generalized DQE” by including a spatial‐frequency‐dependent noise‐power term,, corresponding to background anatomical fluctuations. Cascaded systems analysis (CSA) of the generalized DQE reveals tradeoffs between anatomical noise and the factors that govern quantum noise. We extend such analysis to dual‐energy (DE) imaging, in which the overlying anatomical structure is selectively removed in image reconstructions by combining projections acquired at low and high kVp. The effectiveness of DE imaging in removing anatomical noise is quantified by measurement ofin an anthropomorphic phantom. Combining the generalized DQE with an idealized task function to yield the detectability index, we show that anatomical noise dramatically influences task‐based performance, system design, and optimization. For the case of radiography, the analysis resolves a fundamental and illustrative quandary: The effect of kVp on imaging performance, which is poorly described by conventional DQE analysis but is clarified by consideration of the generalized DQE. For the case of DE imaging, extension of a generalized CSA methodology reveals a potentially powerful guide to system optimization through the optimal selection of the tissue cancellation parameter. Generalized task‐based analysis for DE imaging shows an improvement in the detectability index by more than a factor of 2 compared to conventional radiography for idealized detection tasks.
Impact of multileaf collimator leaf positioning accuracy on intensity modulation radiation therapy quality assurance ion chamber measurements
Authors: Woo M. K. , Nico A.
Published: May 2005

Quality assurance (QA) procedures for intensity modulation radiation therapy (IMRT) usually involve an ion chamber measurement in a phantom using the beam configuration of the actual treatment plan. In our QA procedures it was observed that the degree of agreement between the measurement and the calculation could vary from plan to plan, from linac to linac, as well as over time, with a discrepancy up to 8%. In this paper we examine one aspect of the process which can contribute to such poor reproducibility, namely, the leaf end position accuracy. A series of measurements was designed to irradiate an ion chamber using small beam segments where one multileaf collimator (MLC) edge covers half of the chamber. It was shown that the reproducibility varied up to 13%, which provides a possible explanation for the observed discrepancies above. A useful tool was also developed to measure ionization signals from individual segments of an IMRT sequence. In addition, an understanding of the leaf end position variations offers some insight into the overall quality of an IMRT dose distribution.
From Dimming to Brightening: Decadal Changes in Solar Radiation at Earth's Surface
Authors: Wild Martin , Gilgen Hans , Roesch Andreas , Ohmura Atsumu , Long Charles N. , Dutton Ellsworth G. , Forgan Bruce , Kallis Ain , Russak Viivi , Tsvetkov Anatoly
Published: May 2005

Variations in solar radiation incident at Earth's surface profoundly affect the human and terrestrial environment. A decline in solar radiation at land surfaces has become apparent in many observational records up to 1990, a phenomenon known as global dimming. Newly available surface observations from 1990 to the present, primarily from the Northern Hemisphere, show that the dimming did not persist into the 1990s. Instead, a widespread brightening has been observed since the late 1980s. This reversal is reconcilable with changes in cloudiness and atmospheric transmission and may substantially affect surface climate, the hydrological cycle, glaciers, and ecosystems.
Changes in Earth's Albedo Measured by Satellite
Authors: Wielicki Bruce A. , Wong Takmeng , Loeb Norman , Minnis Patrick , Priestley Kory , Kandel Robert
Published: May 2005

NASA global satellite data provide observations of Earth's albedo, i.e., the fraction of incident solar radiation that is reflected back to space. The satellite data show that the last four years are within natural variability and fail to confirm the 6% relative increase in albedo inferred from observations of earthshine from the moon. Longer global satellite records will be required to discern climate trends in Earth's albedo.
Computational Thermostabilization of an Enzyme
Authors: Korkegian Aaron , Black Margaret E. , Baker David , Stoddard Barry L.
Published: May 2005

Thermostabilizing an enzyme while maintaining its activity for industrial or biomedical applications can be difficult with traditional selection methods. We describe a rapid computational approach that identified three mutations within a model enzyme that produced a 10°C increase in apparent melting temperature
T
m
and a 30-fold increase in half-life at 50°C, with no reduction in catalytic efficiency. The effects of the mutations were synergistic, giving an increase in excess of the sum of their individual effects. The redesigned enzyme induced an increased, temperature-dependent bacterial growth rate under conditions that required its activity, thereby coupling molecular and metabolic engineering.
The Optical Resonances in Carbon Nanotubes Arise from Excitons
Authors: Wang Feng , Dukovic Gordana , Brus Louis E. , Heinz Tony F.
Published: May 2005

Optical transitions in carbon nanotubes are of central importance for nanotube characterization. They also provide insight into the nature of excited states in these one-dimensional systems. Recent work suggests that light absorption produces strongly correlated electron-hole states in the form of excitons. However, it has been difficult to rule out a simpler model in which resonances arise from the van Hove singularities associated with the one-dimensional bond structure of the nanotubes. Here, two-photon excitation spectroscopy bolsters the exciton picture. We found binding energies of ∼400 millielectron volts for semiconducting single-walled nanotubes with 0.8-nanometer diameters. The results demonstrate the dominant role of many-body interactions in the excited-state properties of one-dimensional systems.
Fun with Atoms and Molecules
Authors: Yeston Jake
Published: May 2005

The Cartoon Guide to Chemistry
.
By Larry Gonick and Craig Criddle
. HarperResource (HarperCollins), New York, 2005. 255 pp. $16.95, C$23.95. ISBN 0-06-093677-0.

The latest addition to Gornick's comic series provides an informative, graphic, and humorous introduction to the ideas, techniques, and history of chemistry.
Analysis of Human Serum Immunoglobulin G againstO-Acetyl-Positive andO-Acetyl-Negative Serogroup W135 Meningococcal Capsular Polysaccharide
Authors: Giardina Peter C. , Longworth Emma , Evans-Johnson Renee E. , Bessette Michaelene L. , Zhang Hong , Borrow Ray , Madore Dace , Fernsten Philip
Published: May 2005

The capsular polysaccharide ofNeisseria meningitidisserogroup W135 is expressed in bothO-acetyl-positive (OA+) andO-acetyl-negative (OA−) forms. This study investigates the impact of OA status (OA+versus OA−) on serological measurements of anti-W135 immunoglobulin G (IgG) antibodies in immunized adults. W135-specific serum antibody assignments were made for 28 postimmunization sera from adults by enzyme-linked immunosorbent assay using the meningococcal standard reference serum CDC1992. The established IgG concentration in micrograms per milliliter ([IgG]μg/ml) for CDC1992 against OA+antigen (16.2 μg/ml) was used as a reference to assign a concentration of 10.13 μg/ml IgG against OA−antigen by cross-standardization. Overall, the IgG assignments for these sera were higher against OA+antigen (geometric mean concentration [GMC] = 7.16 μg/ml) than against OA−antigen (GMC = 2.84 μg/ml). However, seven sera showed higher specific [IgG]μg/ml values against the OA+antigen than against the OA−antigen. These sera were also distinguished by the inability of fluid-phase OA−antigen to compete for antibody binding to OA+solid-phase antigen. Although there was no overall difference in functional activity measured by complement-mediated serum bactericidal assay (SBA) against OA+and OA−target bacteria (geometric mean titers of 9,642 and 9,045, respectively), three serum specimens showed a large difference in SBA antibody titers against OA+versus OA−W135 target bacteria, which may reflect different epitope specificities for these sera. Our data indicate that, for some sera, the agreement in anti-OA+versus anti-OA−W135 IgG assignments is serum specific and does not reflect the functional (killing) activity in vitro.
Comparison of a New Immunochromatographic Test to Enzyme-Linked Immunosorbent Assay for Rapid Detection of Immunoglobulin M Antibodies to Hepatitis E Virus in Human Sera
Authors: Chen Hsiao Ying , Lu Yang , Howard Teresa , Anderson David , Fong Priscilla Yiquan , Hu Wei-Ping , Chia Chee Poh , Guan Ming
Published: May 2005

An immunochromatographic test for rapid detection of IgM antibodies in patients with acute hepatitis E infection was developed utilizing the well-characterized recombinant protein EP2.1 and monoclonal antibody 4B2. The new rapid test based on a novel reverse-flow technology was able to generate a positive result within 2 to 3 min. Our study showed that this test was able to detect anti-HEV IgM antibodies in 96.7% of the patient samples tested (
n
= 151) while maintaining an excellent specificity of 98.6% with samples from various patient or healthy control groups (total
n
= 208). Furthermore, this rapid test gave a good specificity of 90.9% when tested with rheumatoid factor (RF)-positive sera (RF value of ≤850 IU/ml;
n
= 11) although a higher concentration of RF in samples might cause cross-reactivity. The new test has a good agreement of 97.2% with a kappa value of 0.943 when compared with a reference enzyme-linked immunosorbent assay. The positive predictive value and the negative predictive value for the rapid test thus reached 98.0 and 97.6%, respectively. This is the first rapid, point-of-care test for hepatitis E and will be especially useful for the diagnosis of acute hepatitis E virus infection in field and emergency settings and in resource-poor countries.
Combined Administration of Meningococcal Serogroup B Outer Membrane Vesicle Vaccine and Conjugated Serogroup C Vaccine Indicated for Prevention of Meningococcal Disease Is Safe and Immunogenic
Authors: Aaberge Ingeborg S. , Oster Philipp , Helland Oddveig S. , Kristoffersen Anne-Cathrine , Ypma Ellen , Høiby E. Arne , Feiring Berit , Nøkleby Hanne
Published: May 2005

MenBvac and Menjugate are safe and efficacious vaccines. The purpose of this study was to evaluate safety and immunogenicity of the combination (MenB/C) of the lyophilized active components of the conjugated group C vaccine Menjugate when reconstituted with the full liquid group B outer membrane vesicle vaccine MenBvac compared to MenBvac and Menjugate given separately. At 6-week intervals, healthy adults were given one dose of MenB/C followed by two doses of MenBvac (MenB/C group), three doses of MenBvac (MenB group), or one dose of Menjugate and two doses of placebo (MenC group). Injection site reactions were frequent in all groups. However, most reactions were short lasting and mild or moderate in intensity, and the vaccines were found to be well tolerated, with no vaccine-related serious adverse events. MenB/C was immunogenic with regard to both serogroup B and C meningococci. Both the serum bactericidal assay and the enzyme-linked immunosorbent assay analyses showed that the immune responses of the combination vaccine were similar to the immune responses of its separate components MenBvac and Menjugate for both serogroup B and C. In conclusion, the combined MenB/C vaccine is safe and immunogenic. The two vaccines do not interact negatively with each other and can easily be administered in the same syringe. The induced immune responses suggest that the combined vaccine is likely to confer protection against systemic group B disease caused by the vaccine strain as well as against group C meningococcal disease.
Deoxycytidyl-Deoxyguanosine Oligonucleotide Classes A, B, and C Induce Distinct Cytokine Gene Expression Patterns in Rhesus Monkey Peripheral Blood Mononuclear Cells and Distinct Alpha Interferon Responses in TLR9-Expressing Rhesus Monkey Plasmacytoid Dendritic Cells
Authors: Abel Kristina , Wang Yichuan , Fritts Linda , Sanchez Eleonora , Chung Eugene , Fitzgerald-Bocarsly Patricia , Krieg Arthur M. , Miller Christopher J.
Published: May 2005

To determine if deoxycytidyl-deoxyguanosine oligonucleotides (CpG ODN) can be used effectively as nonspecific inducers of innate immune defenses for preventative or therapeutic interventions in infectious disease models for nonhuman primates, the present study evaluated the response of rhesus monkey peripheral blood mononuclear cells to three different synthetic CpG ODN classes by defining the cytokine gene expression patterns and by characterizing IFN-α/β responses. Depending on the type and dose of CpG ODN used for stimulation, distinct gene expression patterns were induced. CpG ODN class A (CpG-A ODN) and CpG-C ODN, but not CpG-B ODN, were potent inducers of alpha interferon (IFN-α), and this response was due to IFN-α production by TLR9-positive plasmacytoid dendritic cells. Importantly, there was a dose-dependent increase in IFN-α responses to CpG-A ODN but a dose-dependent decrease in IFN-α responses by CpG-B ODN. The most sustained IFN-α response was induced by CpG-A ODN and was associated with a stronger induction of interferon regulatory factor 7 and the induction of several interferon-stimulated genes. In contrast, and independent of the dose, CpG-B ODN were the weakest inducers of IFN-α but the most potent inducers of proinflammatory cytokines. CpG-C ODN induced cytokine gene expression patterns that were intermediate between those of CpG-A and CpG-B ODN. Thus, the different types of CpG ODN induce different post-TLR9 signaling pathways that result in distinct cytokine gene expression patterns. Based on these findings, A and C class CpG ODN, but not B class CpG ODN, may be particularly suited for use as therapeutic or prophylactic antiviral interventions.
Association of Selected Phenotypic Markers of Lymphocyte Activation and Differentiation with Perinatal Human Immunodeficiency Virus Transmission and Infant Infection
Authors: Lambert John S. , Moye Jack , Plaeger Susan F. , Stiehm E. Richard , Bethel James , Mofenson Lynne M. , Mathieson Bonnie , Kagan Jonathan , Rosenblatt Howard , Paxton Helene , Suter Hildie , Landay Alan
Published: May 2005

This study of a subset of women and infants participating in National Institutes of Health Pediatric AIDS Clinical Trials Group protocol 185 evaluated lymphocyte phenotypic markers of immune activation and differentiation to determine their association with the likelihood of human immunodeficiency virus (HIV) transmission from the women to their infants and the potential for early identification and/or prognosis of infection in the infants. Lymphocytes from 215 human immunodeficiency virus type 1 (HIV)-infected women and 192 of their infants were analyzed by flow cytometry with an extended three-color panel of monoclonal antibodies. Women who did not transmit to their infants tended to have higher CD4
+
T cells. Most notably, levels of total CD8
+
T cells and CD8
+
CD38
+
cells made significant independent contributions to predicting the risk of mother-to-child transmission. Adjusting for HIV-1 RNA level at entry, a one percentage-point increase in these marker combinations was associated with a nine percent increase in the likelihood of maternal transmission. Total as well as naïve CD4
+
T cells were significantly higher in uninfected than infected infants. Total CD8
+
cells, as well as CD8
+
cells positive for HLA-DR
+
, CD45 RA
+
HLA-DR
+
, and CD28
+
HLA-DR
+
were elevated in infected infants. Detailed immunophenotyping may be helpful in predicting which pregnant HIV-infected women are at increased risk of transmitting HIV to their infants. Increasing differences in lymphocyte subsets between infected and uninfected infants became apparent as early as six weeks of age. Detailed immunophenotyping may be useful in supporting the diagnosis of HIV infection in infants with perinatal HIV exposure.
Association of Uterine and Salpingeal Fibrosis with Chlamydial Hsp60 and Hsp10 Antigen-Specific Antibodies inChlamydia-Infected Koalas
Authors: Higgins Damien P. , Hemsley Susan , Canfield Paul J.
Published: May 2005

Infection byChlamydia pneumoniaeorChlamydia pecorumcommonly causes chronic, fibrotic disease of the urogenital tracts of female koalas. Studies of humans have associated titers of serum immunoglobulin G (IgG) against chlamydial hsp60 and hsp10 antigens with chronic infection, salpingeal fibrosis, and tubal infertility. To determine whether a similar relationship exists inChlamydia-infected koalas, samples were collected opportunistically from 34 wild female koalas and examined by gross pathology and histopathology, PCR, and immunohistochemistry forChlamydiaspp. and enzyme-linked immunosorbent assay for serological responses to chlamydial hsp10 and hsp60 antigens. Greater anti-hsp titers occurred inChlamydia-infected koalas with fibrous occlusion of the uterus or uterine tube than in otherChlamydia-infected koalas (for hsp10 IgG,P= 0.005; for hsp60 IgG,P= 0.001; for hsp10 IgA,P= 0.04; for hsp60 IgA,P= 0.09). However, as in humans, some koalas with tubal occlusion had low titers. AmongChlamydia-infected koalas with tubal occlusion, those with low titers were more likely to have an active component to their ongoing uterine or salpingeal inflammation (P= 0.007), such that the assay predicted, with 79% sensitivity and 92% specificity, tubal occlusion where an active component of inflammation was absent. Findings of this study permit advancement of clinical and epidemiological studies of host-pathogen-environment interactions and pose intriguing questions regarding the significance of the Th1/Th2 paradigm and antigen-presenting and inflammation-regulating capabilities of uterine epithelial cells and the roles of latency and reactivation of chlamydial infections in pathogenesis of upper reproductive tract disease of koalas.
Reliability of CD4 Quantitation in Human Immunodeficiency Virus-Positive Children: Implications for Definition of Immunologic Response to Highly Active Antiretroviral Therapy
Authors: Carey Vincent J. , Pahwa Savita , Weinberg Adriana
Published: May 2005

Our objective was to develop data-based algorithms for definition of immunologic response to AIDS therapies in pediatric patients, taking account of T-cell subset measurement errors. The study design involved cross-protocol analysis of 2,148 enrollees in six completed Pediatric AIDS Clinical Trials Group trials. We used standard quantitation of T-cell subsets; linear modeling with mean-dependent measurement error variance was used to develop 95% tolerance limits for change in CD4%. For individuals with a CD4% of approximately 25%, the measurement error-based 95% tolerance interval ranges from 15% to 35%, whereas for individuals with a CD4% of approximately 5%, the tolerance interval ranges from 3% to 7%. When pairs of CD4% measures taken within a time interval of less than 30 days are averaged to estimate steady-state CD4%, tolerance interval width decreases by approximately 30%. A simple graphical tool that provides a data-based criterion for immunologic response over and above variation ascribable to T-cell measurement error is provided. Variability in CD4% due to measurement error is substantial, increases with level of CD4%, and complicates assessment of immunologic response to therapy. Replicates of CD4% measures could be used to improve precision of interpretation of CD4% measures.
Cytokine Gene Expression in Response to SnSAG1 in Horses with Equine Protozoal Myeloencephalitis
Authors: Spencer Jennifer A. , Deinnocentes Patricia , Moyana Edith M. , Guarino Anthony J. , Ellison Siobhan E. , Bird R. Curtis , Blagburn Byron L.
Published: May 2005

Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome seen in horses from the Americas and is mainly caused bySarcocystis neurona. Recently, a 29-kDa surface antigen fromS. neuronamerozoites was identified as being highly immunodominant on a Western blot. This antigen has been sequenced and cloned, and the expressed protein has been named SnSAG1. In a previous study, cell-mediated immune responses to SnSAG1 were shown to be statistically significantly reduced in horses with EPM in comparison to EPM-negative control horses. It therefore appears as though the parasite is able to induce immunosuppression towards parasite-derived antigens as parasite-specific responses are decreased. Isolated peripheral blood lymphocytes from 21 EPM (cerebrospinal fluid [CSF] Western blot)-negative horses with no clinical signs and 21 horses with clinical signs of EPM (CSF Western blot positive) were cocultured with SnSAG1 for 48 and 72 h, and the effect on cytokine production was investigated by means of reverse transcriptase PCR. Cytokines assayed include gamma interferon (IFN-γ), tumor necrosis factor alpha, interleukin (IL)-2, IL-4, and IL-6. β-Actin was used as the housekeeping gene. A Wilcoxon signed-rank test of the findings indicated that there was a statistically significant decrease in IFN-γ production after 48 h in culture for samples from horses with clinical disease. There was also a statistically significant increase in IL-4 production after 72 h in culture for samples from horses with EPM. These results further support the notion that this parasite is able to subvert the immune system in horses with clinical disease.
Prevalence and Persistence of
Chlamydia pneumoniae
Antibodies in Healthy Laboratory Personnel in Finland
Authors: Paldanius Mika , Bloigu Aini , Alho Marianne , Leinonen Maija , Saikku Pekka
Published: May 2005

The rates of
Chlamydia pneumoniae
seroconversions suggesting acute primary infections or reinfections and the prevalences of antibodies were followed up among healthy laboratory workers. Annual serum samples were collected from 47 persons in Helsinki from 1958 to 1990 and from 40 persons in Oulu from 1994 to 1999.
C. pneumoniae
species-specific immunoglobulin G (IgG), IgA, and IgM antibodies were measured by microimmunofluorescence (MIF) in 407 sera from Helsinki. The 185 sera collected in Oulu were tested both by MIF and by commercial enzyme immunoassay (EIA). During the follow-up periods of 31 years in Helsinki and 6 years in Oulu, seroconversions were demonstrated by MIF in 45% and 15% of the study groups, respectively. In Helsinki 9% of the persons seroconverted twice during the follow-up period. By MIF, the total incidence rate per 100 person-years at risk was 6.9 in Helsinki and 4.9 in Oulu, and annual incidence rates varied from 0 to 15.4. By EIA, annual incidence rates in Oulu varied from 0 to 10.8. The seroconversions by MIF were usually not confirmed by EIA and vice versa. Prevalence and persistence rates, respectively, of IgA antibodies were higher in EIA (62% and 26%) than in MIF (26% and 17%), whereas the figures for IgG were quite similar. The prevalence of IgG and IgA antibodies was higher in older persons than in younger ones. The presence of antibodies did not offer protection from reinfection.
Enzyme-Linked Immunosorbent Assay for Pharmacological Studies Targeting Hypoxia-Inducible Factor 1α
Authors: Formento J. L. , Berra E. , Ferrua B. , Magné N. , Simos G. , Brahimi-Horn C. , Pouysségur J. , Milano G.
Published: May 2005

Hypoxia-inducible factor 1 (HIF-1) activates the transcription of a wide range of genes related to oxygen delivery and metabolic adaptation under hypoxic (low-oxygen) conditions. HIF-1 is, in fact, a heterodimer of two subunits, HIF-1α and HIF-1β. The only analytical methods available for measuring HIF-1α levels in tumors are immunohistochemistry and Western blotting. Immunohistochemistry has the advantage of allowing the identification and direct examination of HIF-1α-expressing cells, but has the intrinsic limitation, as for Western blotting, of being nonquantitative. We developed and validated an enzyme-linked immunosorbent assay (ELISA) approach to measure HIF-1α levels in cultured tumor cell lines in vitro. HIF-1α was expressed in thirteen tumor cell lines grown under hypoxic conditions; however, the levels differed strongly between cell lines. These data point to intrinsic differences between cell lines for the induction of HIF-1α under hypoxic conditions. The ELISA developed in the present study is thus an interesting alternative to other analytical methods used to measure HIF-1α protein levels and should be useful in preclinical pharmacological studies targeting HIF-1α.
Persistence of Antibodies to West Nile Virus in Naturally Infected Rock Pigeons (
Columba livia
)
Authors: Gibbs Samantha E. J. , Hoffman Douglas M. , Stark Lillian M. , Marlenee Nicole L. , Blitvich Bradley J. , Beaty Barry J. , Stallknecht David E.
Published: May 2005

Wild caught rock pigeons (
Columba livia
) with antibodies to West Nile virus were monitored for 15 months to determine antibody persistence and compare results of three serologic techniques. Antibodies persisted for the entire study as detected by epitope-blocking enzyme-linked immunosorbent assay and plaque reduction neutralization test. Maternal antibodies in squabs derived from seropositive birds persisted for an average of 27 days.
Evaluation of Commercial Assay Detecting Specific Immunoglobulin G in Oral Fluid for Determining Measles Immunity in Vaccinees
Authors: Kremer Jacques R. , Muller Claude P.
Published: May 2005

A commercial assay for detection of measles immunoglobulin G (IgG) in oral fluid was evaluated in a highly vaccinated cohort using serum IgG as gold standard. In contrast to previous studies from cohorts protected by natural immunity, antibody prevalence was significantly underestimated (−7.4%; confidence interval: −1.5 to −13.2%;
P
= 0.01) due to a reduced sensitivity when antibody levels were low.
Multiple Autoantigen Mimotopes of Infectious Agents Induce Autoimmune Arthritis and Uveitis in Lewis Rats
Authors: Wildner Gerhild , Diedrichs-Moehring Maria
Published: May 2005

We found multimolecular antigenic mimicry of arthritogenic autoantigens and peptides from several other “self” or foreign antigens sharing amino acid sequence homologies. Many of these new mimotopes induced arthritis and/or uveitis upon immunization in Lewis rats, indicating a role for multiple antigens in the initiation of a certain autoimmune disease.
Construction and Expression of Recombinant Streptolysin-O and Preevaluation of Its Use in Immunoassays
Authors: Velázquez Blanca , Massaldi Hugo , Battistoni Julio , Chabalgoity José A.
Published: May 2005

Commercially available immunoassays for assessment of anti-streptolysin-O antibodies use native streptolysin-O obtained by a complex process. We prepared a biologically active recombinant streptolysin-O with higher yield and a simpler purification process. An enzyme-linked immunosorbent assay developed with this recombinant showed good correlation with a commercial test, suggesting that it could be suitable for immunoassays.
Management of chronic heart failure: perceived needs of general practitioners in light of the new general medical services contract
Authors: Leslie S J , McKee S P , Imray E A , Denvir M A
Published: May 2005

Background

Despite the existence of several chronic heart failure (CHF) guidelines the treatment of patients with CHF is suboptimal. The new general medical services (GMS) contract in primary care has only three specific performance indicators for patients with left ventricular dysfunction. The aim of this current questionnaire survey was to assess the views of general practitioners (GPs) on CHF treatments and services in light of the new GMS contract.

Methods and Results

All local GPs (717) were sent a questionnaire. Fifty three per cent were returned. Forty five per cent of GPs had access to a community CHF nurse. Having read a national guideline (SIGN) and having the support of a CHF nurse did not seem to affect the knowledge of GPs in terms of perceived benefits of drug treatments. GPs with access to a specialist CHF nurse service attached more importance to it than those with no specialist nurse (p = 0.003).

Conclusions

Most GPs were aware of the existence of a national guideline but many had not read it. There was little or no difference in the knowledge level for various evidence based treatments between GPs who had or had not read the guideline suggesting that reading guidelines may not be a key factor in determining knowledge. Support for a specialist CHF nurse was higher among GPs who already had this service, suggesting that this service is valued. The new GMS contract may improve identification and diagnosis of patients with CHF but there is a danger that it may fall short of ensuring optimal treatment for patients with CHF.
What caused the Black Death?
Authors: Duncan C J , Scott S
Published: May 2005

For the whole of the 20th century it was believed that the Black Death and all the plagues of Europe (1347–1670) were epidemics of bubonic plague. This review presents evidence that this view is incorrect and that the disease was a viral haemorrhagic fever, characterised by a long incubation period of 32 days, which allowed it to be spread widely even with the limited transport of the Middle Ages. It is suggested that haemorrhagic plague emerged from its animal host in Ethiopia and struck repeatedly at European/Asian civilisations, before appearing as the Black Death. The CCR5-Δ32 mutation confers protection against HIV-1 in an average of 10% of the people of European origin today. It is suggested that all the Δccr5 alleles originated from a single mutation event that occurred before 1000 bc and the subsequent epidemics of haemorrhagic plague gently forced up its frequency to 5×10−5 at the time of the Black Death. Epidemics of haemorrhagic plague over the next three centuries then steadily raised the frequency in Europe (but not elsewhere) to present day values.