bluuebunny/crossref_metadata_2025 huggingface dataset:
Secretion and gene expression of inhibin, oxytocin and steroid hormones during the in vitro differentiation of bovine granulosa cells
Authors: Luck MR , Rodgers RJ , Findlay JK
Published: January 2006

Bovine granulosa cells were cultured under defined conditions to examine (1) their secretion of immunoreactive inhibin, oxytocin, progesterone and oestradiol during differentiation in vitro; (2) their expression, by Northern analysis, of specific mRNAs for inhibin and oxytocin as compared with uncultured cells; (3) possible interrelationships between the four secreted hormones; and (4) the hypothesis that androgens and steroidogenesis influence the secretion of inhibin. The secretion of inhibin and oestradiol fell rapidly over the first few days of culture but remained at detectable levels for at least 7 days. Conversely, the secretion of oxytocin and progesterone rose steadily as culture progressed. These changes occurred spontaneously (i.e. without gonadotrophin treatment) and were not dependent on the addition of serum to the culture medium. Messenger RNAs for the inhibin alpha- and beta A-subunits were present in uncultured cells but barely detectable or undetectable in cells cultured for 4 days. Conversely, the mRNA for oxytocin, which was not detectable in uncultured cells, was present in cultured cells and increased in quantity as culture progressed. Treatment of cells with testosterone (5 nM-5 microM), in the presence or absence of serum (10% FCS), had no effect on the secretion of inhibin but stimulated the declining oestradiol secretion. Treatment with ascorbic acid (0.5 mM) increased the secretion of oxytocin and progesterone, as previously described, but not that of inhibin. Treatment with aminoglutethimide (0.5 mM), an inhibitor of steroidogenesis, substantially inhibited progesterone secretion and the response of oestradiol secretion to testosterone, but had no effect on the secretion of either inhibin or oxytocin. We conclude that bovine granulosa cells differentiate spontaneously in defined culture in a manner that, as defined by the secretion of steroid and peptide hormones, closely resembles their luteinization in vivo. The switch in protein hormone secretion from inhibin to oxytocin is accompanied by a corresponding change in mRNA expression. The changes in steroid and peptide hormone secretions that take place in culture appear to occur independently of one another although their absolute cause remains to be determined. In contrast to previous studies, we could find no evidence for the regulation of inhibin secretion by either androgens or steroidogenesis.
Taxonomic revision of Leptomeria (Santalaceae)
Authors: Lepschi B.J.
Published: January 2006

The endemic Australian genus Leptomeria(Santalaceae) is revised. Seventeen
species are recognised, and two of these,L. ellytesand
L. furtiva, are described as new. A key, descriptions,
notes and distribution maps are provided for all species, as well as
illustrations for selected taxa.
Annotated and illustrated survey of the marine macroalgae from Motupore Island and vicinity (Port Moresby area, Papua New Guinea). III. Rhodophyta
Authors: Millar Alan J. K. , De Clerck Olivier , Coppejans Eric , Liao Lawrence M.
Published: January 2006

The marine benthic red algae of Motupore Island and vicinity (Port Moresby
area, Papua New Guinea [PNG]) are documented and 36 of the 161
species are illustrated. All records are listed with bibliographic,
biogeographic, taxonomic and nomenclatural comments. Apart from several
undescribed taxa, which we are in the process of describing separately, none
is endemic to the island at this stage. The discovery of the east Australian
species Gracilaria rhodymenioides represents a
substantial range extension as does Ceramium lentiforme
from New South Wales. One species of Gibsmithia also
represents a significant range extension from its Lord Howe Island, Norfolk
Island and southern Great Barrier Reef distributions.
Platoma ardreanum is reported from outside its Hawaiian
distribution for the first time, and the Caribbean
Renouxia antillana represents a major range extension
for the Pacific. Forty-four species appear to be newly recorded for the PNG
marine flora and 108 are new records for the Island itself. Because all
collections were taken during the month of July, many seasonal entities may be
missing from this list and the total marine flora is not yet known. Moreover,
because previous records are quite detailed with respect to epiphytic and turf
algae, we have not concentrated on these species. The non-geniculate coralline
algae have only been collected sporadically as part of this survey.
The activity of a human endoplasmic reticulum-associated degradation E3, gp78, requires its Cue domain, RING finger, and an E2-binding site
Authors: Chen Bo , Mariano Jennifer , Tsai Yien Che , Chan Anna H. , Cohen Mickael , Weissman Allan M.
Published: January 2006

Efficient targeting of proteins for degradation from the secretory pathway is essential to homeostasis. This occurs through endoplasmic reticulum (ER)-associated degradation (ERAD). In this study, we establish that a human ubiquitin ligase (E3), gp78, and a specific E2, Ube2g2, are both critically important for ERAD of multiple substrates. gp78 exhibits a complex domain structure that, in addition to the RING finger, includes a ubiquitin-binding Cue domain and a specific binding site for Ube2g2. Disruption of either of these domains abolishes gp78-mediated ubiquitylation and protein degradation, resulting in accumulation of substrates in their fully glycosylated forms in the ER. This suggests that gp78-mediated ubiquitylation is an early step in ERAD that precedes dislocation of substrates from the ER. The
in vivo
requirement for both an E2-binding site distinct from the RING finger and a ubiquitin-binding domain intrinsic to an E3 suggests a previously unappreciated level of complexity in ubiquitin ligase function. These results also provide proof of principle that interrupting a specific E2-E3 interaction can selectively inhibit ERAD.
Phase coexistence and connectivity in the apical membrane of polarized epithelial cells
Authors: Meder Doris , Moreno Maria Joao , Verkade Paul , Vaz Winchil L. C. , Simons Kai
Published: January 2006

Although it is well described in model membranes, little is known about phase separation in biological membranes. Here, we provide evidence for a coexistence of at least two different lipid bilayer phases in the apical plasma membrane of epithelial cells. Phase connectivity was assessed by measuring long-range diffusion of several membrane proteins by fluorescence recovery after photobleaching in two polarized epithelial cell lines and one fibroblast cell line. In contrast to the fibroblast plasma membrane, in which all of the proteins diffused with similar characteristics, in the apical membrane of epithelial cells the proteins could be divided into two groups according to their diffusion characteristics. At room temperature (≈25°C), one group showed fast diffusion and complete recovery. The other diffused three to four times slower and, more importantly, displayed only partial recovery. Only the first group comprises proteins that are believed to be associated with lipid rafts. The partial recovery is not caused by topological constraints (microvilli, etc.), cytoskeletal constraints, or protein-protein interactions, because all proteins show 100% recovery in fluorescence recovery after photobleaching experiments at 37°C. In addition, the raft-associated proteins cannot be coclustered by antibodies on the apical membrane at 12°C. The interpretation that best fits these data is that the apical membrane of epithelial cells is a phase-separated system with a continuous (percolating) raft phase <25°C in which isolated domains of the nonraft phase are dispersed, whereas at 37°C the nonraft phase becomes the continuous phase with isolated domains of the raft phase dispersed in it.
Essential genes of a minimal bacterium
Authors: Glass John I. , Assad-Garcia Nacyra , Alperovich Nina , Yooseph Shibu , Lewis Matthew R. , Maruf Mahir , Hutchison Clyde A. , Smith Hamilton O. , Venter J. Craig
Published: January 2006

Mycoplasma genitalium
has the smallest genome of any organism that can be grown in pure culture. It has a minimal metabolism and little genomic redundancy. Consequently, its genome is expected to be a close approximation to the minimal set of genes needed to sustain bacterial life. Using global transposon mutagenesis, we isolated and characterized gene disruption mutants for 100 different nonessential protein-coding genes. None of the 43 RNA-coding genes were disrupted. Herein, we identify 382 of the 482
M. genitalium
protein-coding genes as essential, plus five sets of disrupted genes that encode proteins with potentially redundant essential functions, such as phosphate transport. Genes encoding proteins of unknown function constitute 28% of the essential protein-coding genes set. Disruption of some genes accelerated
M. genitalium
growth.
Primary steps of the photoactive yellow protein: Isolated chromophore dynamics and protein directed function
Authors: Lee I-Ren , Lee Wonchul , Zewail Ahmed H.
Published: January 2006

The cycle of the photoactive yellow protein (PYP) has been extensively studied, but the dynamics of the isolated chromophore responsible for transduction is unknown. Here, we present real-time observation of the dynamics of the negatively charged chromophore and detection of intermediates along the path of trans-to-cis isomerization using femtosecond mass selection/electron detachment techniques. The results show that the role of the protein environment is not in the first step of double-bond twisting (barrier crossing) but in directing efficient conversion to the cis-structure and in impeding radical formation within the protein.
Targeted Therapeutic Applications of Acoustically Active Microspheres in the Microcirculation
Authors: CHAPPELL JOHN C. , PRICE RICHARD J.
Published: January 2006

The targeted delivery of intravascular drugs and genes across the endothelial barrier with only minimal side effects remains a significant obstacle in establishing effective therapies for many pathological conditions. Recent investigations have shown that contrast agent microbubbles, which are typically used for image enhancement in diagnostic ultrasound, may also be promising tools in emergent, ultrasound–based therapies. Explorations of the bioeffects generated by ultrasound–microbubble interactions indicate that these phenomena may be exploited for clinical utility such as in the targeted revascularization of flow‐deficient tissues. Moreover, development of this treatment modality may also include using ultrasound–microbubble interactions to deliver therapeutic material to tissues, and reporter genes and therapeutic agents have been successfully transferred from the microcirculation to tissue in various animal models of normal and pathological function. This article reviews the recent studies aimed at using interactions between ultrasound and contrast agent microbubbles in the microcirculation for therapeutic purposes. Furthermore, the authors present investigations involving microspheres that are of a different design compared to current microbubble contrast agents, yet are acoustically active and demonstrate potential as tools for targeted delivery. Future directions necessary to address current challenges and advance these techniques to clinical practicality are also discussed.
Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. I. Thyroid and Reproductive Effects
Authors: York Raymond G. , Lewis Elise , Brown W. Ray , Girard Michael F. , Mattie David R. , Funk Kathleen A. , Strawson Joan S.
Published: January 2006

A recent study further investigated the potential effects of maternal thyroid function and morphology on fetal development upon maternal exposure to ammonium perchlorate during gestation and lactation. Female Sprague-Dawley rats (25/group) were given continual access to 0 (carrier), 0.01, 0.1, 1.0, and 30.0 mg/kg-day perchlorate in drinking water beginning 2 weeks prior to cohabitation through lactation day 10. Maternal, fetal, and pup serum thyroid hormone (thyroid-stimulating hormone [TSH], triiodo thyronine [T3], thyroxine [T4]) levels and thyroid histopathology were evaluated on gestation day 21, and lactation days 5, 10, and 22. No effects of exposure were observed on cesarean-sectioning, litter parameters, or fetal alterations. Reproductive parameters, including gestation length, number of implants, litter size, pup viability, and lactation indices, were comparable among all groups. Thyroid weights of dams sacrificed on gestation day 21, and lactation days 10 and 22 were significantly increased at 30.0 mg/kg-day. Increased thyroid weights were observed in male and female pups as early as postpartum days 5 and 10, respectively. Changes in maternal and neonatal thyroid histopathology were detectable at 1.0 mg/kg-day exposure. The maternal no-observable-effect level (NOEL) was 0.1 mg/kg-day (follicular cell hyperplasia was present at 1.0 and 30.0 mg/kg-day). The developmental NOEL was less than 0.01 mg/kg-day; thyroid weights of postpartum day 10 pups were increased at all exposures. Colloid depletion at 1.0 and 30.0 mg/kg-day exposures and changes of hormone levels at all exposures were considered an adaptive effect and appeared reversible in the rodent.
15q Duplication associated with autism in a multiplex family with a familial cryptic translocation t(14;15)(q11.2;q13.3) detected using array‐CGH
Authors: Koochek M , Harvard C , Hildebrand MJ , Van Allen M , Wingert H , Mickelson E , Holden JJA , Rajcan‐Separovic E , Lewis MES
Published: January 2006

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with a strong genetic aetiology. In approximately 1% of cases, duplication of the 15q11‐13 region has been reported. We report the clinical, array‐comparative genomic hybridization (CGH) and cytogenetic evaluation of two individuals from a multiplex family demonstrating autism due to a maternally inherited gain of 15q11‐13. Our findings indicate that unlike most 15q11‐13 gains, which are caused by interstitial duplication of this region or supernumerary marker chromosomes deriving from proximal 15q, the 15q gain in this family is the result of abnormal segregation of a cryptic familial translocation with breakpoints at 14q11.2 and 15q13.3. The affected members of this family were found to have a normal karyotype at >550 band resolution. This translocation was identified using the 1‐Mb resolution whole genome array (Spectral Genomics). The affected individuals have a gain of seven clones from proximal 15q, a loss of two clones from proximal 14q and a gain of two clones from 6q. Fluorescent in situ hybridization (FISH) analysis with clones from chromosomes 14 and 15, combined with DAPI reverse banding, showed an abnormal karyotype with one normal chromosome 15 and the der(15) t(14;15)(q11.2.;q13.3), resulting in the gain of proximal 15q and the loss of proximal 14q in affected individuals. The duplication of two clones from 6q in the affected subjects was also found in unaffected members of the family. Our findings suggest that the gain of 15q in autism may in some cases be due to cryptic translocations with breakpoints in the pericentromic regions of chromosome 15 and a different acrocentric chromosome. Variation in the size of pericentromic regions of any acrocentric chromosome may justify karyotype and FISH studies of autistic probands and their parents using probes from the 15q proximal region to determine recurrence risk for autism in some families.
Health Insurance and Health at Age 65: Implications for Medical Care Spending on New Medicare Beneficiaries
Authors: Hadley Jack , Waidmann Timothy
Published: January 2006

Objectives. To investigate the consequences of endogeneity bias on the estimated effect of having health insurance on health at age 63 or 64, just before most people qualify for Medicare, and to simulate the implications for total and public insurance (Medicare and Medicaid) spending on newly enrolled beneficiaries in their first years of Medicare coverage.

Data. The longitudinal Health and Retirement Survey of people who were 55–61 years old in 1992, followed through biannual surveys to age 63–64 or until 2000 (whichever came first), and those who were 66–70 years olds from the Medicare Current Beneficiary Surveys, 1992–1998.

Study Design. Instrumental variable (IV) estimation of a simultaneous equation model of insurance choice and health at age 63–64 as a function of baseline health and sociodemographic characteristics in 1992 and endogenous insurance coverage over the observation period.

Findings. Continuous insurance coverage is associated with significantly fewer deaths prior to age 65 and, among those who survive, a significant upward shift in the distribution of health states from fair and poor health with disabilities to good to excellent health. Treating insurance coverage as endogenous increases the magnitude of the estimated effect of having insurance on improved health prior to age 65. The medical spending simulations suggest that if the near‐elderly had continuous insurance coverage, average annual medical spending per capita for new Medicare beneficiaries in their first few years of coverage would be slightly lower because of the improvement in health status. In addition, total Medicare and Medicaid spending for new beneficiaries over their first few years of coverage would be about the same or slightly lower, even though more people survive to age 65.

Conclusions. Extending insurance coverage to all Americans between the ages of 55 and 64 would improve health (increase survival and shift people from good–fair–poor health to excellent–very good health) at age 65, and possibly reduce total short‐term spending by Medicare and Medicaid for newly eligible Medicare beneficiaries, even though more people would enter the program because of increased survival.
Patient Turnover and Nursing Staff Adequacy
Authors: Unruh Lynn Y. , Fottler Myron D.
Published: January 2006

Objective. To assess the relative validity of patient turnover adjustments and the difference in nurse staffing using measures that adjust for patient turnover and severity versus those that do not.

Data Sources. Numbers of registered nurses (RNs), adjusted patient days of care (APDC), length of stay, and patient severity information from acute care general hospitals in Pennsylvania 1994–2001, obtained from the Pennsylvania Department of Health, the American Hospital Association, and the Atlas MediQual system.

Study Design. After examining the trends in patient turnover and severity and their relationship to RN staffing, we apply two‐patient turnover indices, with and without patient severity adjustments, to RN staffing measures, and test the difference between the original and adjusted measures using paired sample t‐tests.

Data Extraction Methods. Data sets were match merged by hospital ID, and patient turnover and severity indices were created, using 1994 as the base year. RN staffing measures were developed using unadjusted APDC, and APDC adjusted for patient turnover and both patient turnover and severity.

Principal Findings. Patient turnover increased significantly from 1994 to 2001. The difference between RN staffing measures adjusted for patient turnover and severity and those not adjusted was increasingly significant from 1995 onward. Unadjusted RN staffing showed a 1 percent decline over the 8‐year‐period compared with decreases of from 9 to 26 percent after adjustments.

Conclusions. These results indicate that the assessment of unadjusted RN staffing by RN to patient ratios alone underestimates nursing workload and overstates RN staffing levels. Patient turnover, as well as severity, should be taken into account in staffing assessment and decision making.
Validation of GATE Monte Carlo simulations of the GE Advance/Discovery LS PET scanners
Authors: Schmidtlein C. Ross , Kirov Assen S. , Nehmeh Sadek A. , Erdi Yusuf E. , Humm John L. , Amols Howard I. , Bidaut Luc M. , Ganin Alex , Stearns Charles W. , McDaniel David L. , Hamacher Klaus A.
Published: January 2006

The recently developed GATE (GEANT4 application for tomographic emission) Monte Carlo package, designed to simulate positron emission tomography (PET) and single photon emission computed tomography (SPECT) scanners, provides the ability to model and account for the effects of photon noncollinearity, off‐axis detector penetration, detector size and response, positron range, photon scatter, and patient motion on the resolution and quality of PET images. The objective of this study is to validate a model within GATE of the General Electric (GE) Advance/Discovery Light Speed (LS) PET scanner. Our three‐dimensional PET simulation model of the scanner consists of 12 096 detectors grouped into blocks, which are grouped into modules as per the vendor's specifications. The GATE results are compared to experimental data obtained in accordance with the National Electrical Manufactures Association/Society of Nuclear Medicine (NEMA/SNM), NEMA NU 2‐1994, and NEMA NU 2‐2001 protocols. The respective phantoms are also accurately modeled thus allowing us to simulate the sensitivity, scatter fraction, count rate performance, and spatial resolution. In‐house software was developed to produce and analyze sinograms from the simulated data. With our model of the GE Advance/Discovery LS PET scanner, the ratio of the sensitivities with sources radially offset 0 and from the scanner's main axis are reproduced to within 1% of measurements. Similarly, the simulated scatter fraction for the NEMA NU 2‐2001 phantom agrees to within less than 3% of measured values (the measured scatter fractions are 44.8% and and the simulated scatter fraction is ). The simulated count rate curves were made to match the experimental curves by using deadtimes as fit parameters. This resulted in deadtime values of 625 and at the Block and Coincidence levels, respectively. The experimental peak true count rate of and the peak activity concentration of were matched by the simulated results to within 0.5% and 0.1% respectively. The simulated count rate curves also resulted in a peak NECR of at compared to at from averaged experimental values. The spatial resolution of the simulated scanner matched the experimental results to within .
Image‐fusion of MR spectroscopic images for treatment planning of gliomas
Authors: Chang Jenghwa , Thakur Sunitha , Perera Gerard , Kowalski Alex , Huang Wei , Karimi Sasan , Hunt Margie , Koutcher Jason , Fuks Zvi , Amols Howard , Narayana Ashwatha
Published: January 2006

magnetic resonance spectroscopic imaging (MRSI) can improve the accuracy of target delineation for gliomas, but it lacks the anatomic resolution needed for image fusion. This paper presents a simple protocol for fusing simulation computer tomography (CT) and MRSI images for glioma intensity‐modulated radiotherapy (IMRT), including a retrospective study of 12 patients. Each patient first underwent whole‐brain axial fluid‐attenuated‐inversion‐recovery (FLAIR) MRI (3 mm slice thickness, no spacing), followed by three‐dimensional (3D) MRSI measurements (TE/TR: ) of a user‐specified volume encompassing the extent of the tumor. The nominal voxel size of MRSI ranged from to . A system was developed to grade the tumor using the choline‐to‐creatine (Cho/Cr) ratios from each MRSI voxel. The merged MRSI images were then generated by replacing the Cho/Cr value of each MRSI voxel with intensities according to the Cho/Cr grades, and resampling the poorer‐resolution Cho/Cr map into the higher‐resolution FLAIR image space. The FUNCTOOL processing software was also used to create the screen‐dumped MRSI images in which these data were overlaid with each FLAIR MRI image. The screen‐dumped MRSI images were manually translated and fused with the FLAIR MRI images. Since the merged MRSI images were intrinsically fused with the FLAIR MRI images, they were also registered with the screen‐dumped MRSI images. The position of the MRSI volume on the merged MRSI images was compared with that of the screen‐dumped MRSI images and was shifted until agreement was within a predetermined tolerance. Three clinical target volumes (CTVs) were then contoured on the FLAIR MRI images corresponding to the Cho/Cr grades. Finally, the FLAIR MRI images were fused with the simulation CT images using a mutual‐information algorithm, yielding an IMRT plan that simultaneously delivers three different dose levels to the three CTVs. The image‐fusion protocol was tested on 12 (six high‐grade and six low‐grade) glioma patients. The average agreement of the MRSI volume position on the screen‐dumped MRSI images and the merged MRSI images was 0.29 mm with a standard deviation of 0.07 mm. Of all the voxels with Cho/Cr grade one or above, the distribution of Cho/Cr grade was found to correlate with the glioma grade from pathologic finding and is consistent with literature results indicating Cho/Cr elevation as a marker for malignancy. In conclusion, an image‐fusion protocol was developed that successfully incorporates MRSI information into the IMRT treatment plan for glioma.
Effects on MRI due to altered rf polarization near conductive implants or instruments
Authors: Graf Hansjörg , Steidle Günter , Martirosian Petros , Lauer Ulrike A. , Schick Fritz
Published: January 2006

In magnetic resonance imaging near metal parts variations in radio frequency (rf)‐amplitude and of receive sensitivity must be considered. For loop structures, e.g., vascular stents, produces rf eddy currents in accordance to Faraday's law; the ‐related electrical rf field injects directly to elongated structures (e.g., wires). Locally, the rf magnetic field (induced ) is superimposed onto the rf field from the transmitter coil, which near the metal can dominate spin excitation. Geometry and arrangement of the parts determine the polarization of . Components parallel to are of special interest. A copper sheet (, thick) and a long copper wire were examined in a water phantom using the spin‐echo (SE) technique. In addition to rf‐amplitude amplification, rf‐phase shift due to components of could be detected near the metallic objects. Periodic rf‐amplitude instabilities had an amplified effect for phase‐shifted regions. Phase‐encoding artifacts occurred as distinct ghosts or band‐like smearing from affected spin ensembles. SE phase imaging can potentially be used in interventional magnetic resonance imaging for background‐free localization of metallic markers.
Iterative three‐dimensional expectation maximization restoration of single photon emission computed tomography images: Application in striatal imaging
Authors: Gantet Pierre , Payoux Pierre , Celler Anna , Majorel Cynthia , Gourion Daniel , Noll Dominikus , Esquerré Jean‐Paul
Published: January 2006

Single photon emission computed tomography imaging suffers from poor spatial resolution and high statistical noise. Consequently, the contrast of small structures is reduced, the visual detection of defects is limited and precise quantification is difficult. To improve the contrast, it is possible to include the spatially variant point spread function of the detection system into the iterative reconstruction algorithm. This kind of method is well known to be effective, but time consuming. We have developed a faster method to account for the spatial resolution loss in three dimensions, based on a postreconstruction restoration method. The method uses two steps. First, a noncorrected iterative ordered subsets expectation maximization (OSEM) reconstruction is performed and, in the second step, a three‐dimensional (3D) iterative maximum likelihood expectation maximization (ML‐EM) a posteriori spatial restoration of the reconstructed volume is done. In this paper, we compare to the standard OSEM‐3D method, in three studies (two in simulation and one from experimental data). In the two first studies, contrast, noise, and visual detection of defects are studied. In the third study, a quantitative analysis is performed from data obtained with an anthropomorphic striatal phantom filled with 123‐I. From the simulations, we demonstrate that contrast as a function of noise and lesion detectability are very similar for both OSEM‐3D and OSEM‐R methods. In the experimental study, we obtained very similar values of activity‐quantification ratios for different regions in the brain. The advantage of OSEM‐R compared to OSEM‐3D is a substantial gain of processing time. This gain depends on several factors. In a typical situation, for a acquisition of 120 projections, OSEM‐R is 13 or 25 times faster than OSEM‐3D, depending on the calculation method used in the iterative restoration. In this paper, the OSEM‐R method is tested with the approximation of depth independent resolution. For the striatum this approximation is appropriate, but for other clinical situations we will need to include a spatially varying response. Such a response is already included in OSEM‐3D.
Toward objective and quantitative evaluation of imaging systems using images of phantoms
Authors: Gagne Robert M. , Gallas Brandon D. , Myers Kyle J.
Published: January 2006

The use of imaging phantoms is a common method of evaluating image quality in the clinical setting. These evaluations rely on a subjective decision by a human observer with respect to the faintest detectable signal(s) in the image. Because of the variable and subjective nature of the human‐observer scores, the evaluations manifest a lack of precision and a potential for bias. The advent of digital imaging systems with their inherent digital data provides the opportunity to use techniques that do not rely on human‐observer decisions and thresholds. Using the digital data, signal‐detection theory (SDT) provides the basis for more objective and quantitative evaluations which are independent of a human‐observer decision threshold. In a SDT framework, the evaluation of imaging phantoms represents a “signal‐known‐exactly/background‐known‐exactly” (“SKE/BKE”) detection task. In this study, we compute the performance of prewhitening and nonprewhitening model observers in terms of the observer signal‐to‐noise ratio (SNR) for these “SKE/BKE” tasks. We apply the evaluation methods to a number of imaging systems. For example, we use data from a laboratory implementation of digital radiography and from a full‐field digital mammography system in a clinical setting. In addition, we make a comparison of our methods to human‐observer scoring of a set of digital images of the CDMAM phantom available from the internet (EUREF—European Reference Organization). In the latter case, we show a significant increase in the precision of the quantitative methods versus the variability in the scores from human observers on the same set of images. As regards bias, the performance of a model observer estimated from a finite data set is known to be biased. In this study, we minimize the bias and estimate the variance of the observer SNR using statistical resampling techniques, namely, “bootstrapping” and “shuffling” of the data sets. Our methods provide objective and quantitative evaluation of imaging systems with increased precision and reduced bias.
Study of scattered photons from the collimator system of Leksell Gamma Knife using the EGS4 Monte Carlo Code
Authors: Cheung Joel Y. C. , Yu K. N.
Published: January 2006

In the algorithm of Leksell GAMMAPLAN (the treatment planning software of Leksell Gamma Knife), scattered photons from the collimator system are presumed to have negligible effects on the Gamma Knife dosimetry. In this study, we used the EGS4 Monte Carlo (MC) technique to study the scattered photons coming out of the single beam channel of Leksell Gamma Knife. The PRESTA (Parameter Reduced Electron‐Step Transport Algorithm) version of the EGS4 (Electron Gamma Shower version 4) MC computer code was employed. We simulated the single beam channel of Leksell Gamma Knife with the full geometry. Primary photons were sampled from within the source and radiated isotropically in a solid angle of . The percentages of scattered photons within all photons reaching the phantom space using different collimators were calculated with an average value of 15%. However, this significant amount of scattered photons contributes negligible effects to single beam dose profiles for different collimators. Output spectra were calculated for the four different collimators. To increase the efficiency of simulation by decreasing the semiaperture angle of the beam channel or the solid angle of the initial directions of primary photons will underestimate the scattered component of the photon fluence. The generated backscattered photons from within the source and the beam channel also contribute to the output spectra.
A method to improve visual similarity of breast masses for an interactive computer‐aided diagnosis environment
Authors: Zheng Bin , Lu Amy , Hardesty Lara A. , Sumkin Jules H. , Hakim Christiane M. , Ganott Marie A. , Gur David
Published: January 2006

The purpose of this study was to develop and test a method for selecting “visually similar” regions of interest depicting breast masses from a reference library to be used in an interactive computer‐aided diagnosis (CAD) environment. A reference library including 1000 malignant mass regions and 2000 benign and CAD‐generated false‐positive regions was established. When a suspicious mass region is identified, the scheme segments the region and searches for similar regions from the reference library using a multifeature based ‐nearest neighbor (KNN) algorithm. To improve selection of reference images, we added an interactive step. All actual masses in the reference library were subjectively rated on a scale from 1 to 9 as to their “visual margins speculations.” When an observer identifies a suspected mass region during a case interpretation he/she first rates the margins and the computerized search is then limited only to regions rated as having similar levels of spiculation (within scale difference). In an observer preference study including 85 test regions, two sets of the six “similar” reference regions selected by the KNN with and without the interactive step were displayed side by side with each test region. Four radiologists and five nonclinician observers selected the more appropriate (“similar”) reference set in a two alternative forced choice preference experiment. All four radiologists and five nonclinician observers preferred the sets of regions selected by the interactive method with an average frequency of 76.8% and 74.6%, respectively. The overall preference for the interactive method was highly significant . The study demonstrated that a simple interactive approach that includes subjectively perceived ratings of one feature alone namely, a rating of margin “spiculation,” could substantially improve the selection of “visually similar” reference images.
Monte Carlo characterization of an ytterbium‐169 high dose rate brachytherapy source with analysis of statistical uncertainty
Authors: Medich David C. , Tries Mark A. , Munro John J.
Published: January 2006

An ytterbium‐169 high dose rate brachytherapy source, distinguished by an intensity‐weighted average photon energy of and a half‐life, is characterized in terms of the updated AAPM Task Group Report No. 43 specifications using the MCNP5 Monte Carlo computer code. In accordance with these specifications, the investigation included Monte Carlo simulations both in water and air with the in‐air photon spectrum filtered to remove low‐energy photons below . TG‐43 dosimetric data including , , , , , , and were calculated and statistical uncertainties in these parameters were derived and calculated in the appendix.
Benign mesothelioma of the appendix: an incidental finding in a case of sigmoid diverticular disease
Authors: Bansal A , Zakhour H D
Published: January 2006

Benign multicystic mesothelioma is a well recognised but rare entity. The aim of this report is to describe a case of a small mesothelial proliferation of the peritoneum. A 58 year old postmenopausal woman presented with left sided abdominal pain and altered bowel habit. Radiological investigations (barium enema and computed tomography scan of the abdomen and pelvis) were undertaken. An operation was performed for symptomatic sigmoid diverticular disease. Unusually, the appendix was adherent to the sigmoid colon. Microscopy revealed a benign mesothelioma. The patient remains symptom free to date.
Clinical relevance of Fas expression in oesophageal squamous cell carcinoma
Authors: Chan K W , Lee P Y , Lam A K Y , Law S , Wong J , Srivastava G
Published: January 2006

Aims:To determine the extent of Fas expression in oesophageal squamous cell carcinomas (ESCCs) from Chinese patients and to correlate Fas expression with clinicopathological prognostic parameters.

Methods:Clinicopathological data were collected from 58 patients with ESCC who underwent oesophagectomy and had no prior radiotherapy or chemotherapy. Immunostaining was performed on the primary tumours. Expression of Fas was correlated with patients’ demographics, tumour characteristics and stage, R category of surgery, and patients’ survival.

Results:The actuarial survival rates of all patients at two and five years after surgery were 48% and 14%, respectively. Fas expression was detected in 89.7% of ESCCs. Higher Fas expression recorded on a four point scale correlated with better tumour differentiation (p < 0.01), but not with other patient or tumour variables. Importantly, higher Fas expression was associated with better survival (p  =  0.0317).

Conclusions:These findings suggest that Fas activated apoptosis is important in the pathogenesis of ESCC. This molecular pathway may be a potential therapeutic target for ESCC.
Altered metabolism and mitochondrial genome in prostate cancer
Authors: Dakubo G D , Parr R L , Costello L C , Franklin R B , Thayer R E
Published: January 2006

Mutations in mitochondrial DNA are frequent in cancer and the accompanying mitochondrial dysfunction and altered intermediary metabolism might contribute to, or signal, tumour pathogenesis. The metabolism of human prostate peripheral zone glandular epithelial cells is unique. Compared with many other soft tissues, these glandular epithelial cells accumulate high concentrations of zinc, which inhibits the activity of m-aconitase, an enzyme involved in citrate metabolism through Krebs cycle. This causes Krebs cycle truncation and accumulation of high concentrations of citrate to be secreted in prostatic fluid. The accumulation of zinc also inhibits terminal oxidation. Therefore, these cells exhibit inefficient energy production. In contrast, malignant transformation of the prostate is associated with an early metabolic switch, leading to decreased zinc accumulation and increased citrate oxidation. The efficient energy production in these transformed cells implies increased electron transport chain activity, increased oxygen consumption, and perhaps, excess reactive oxygen species (ROS) production compared with normal prostate epithelial cells. Because ROS have deleterious effects on DNA, proteins, and lipids, the altered intermediary metabolism may be linked with ROS production and accelerated mitochondrial DNA mutations in prostate cancer.
FOREST DIAGRAMS FOR ELEMENTS OF THOMPSON'S GROUP F
Authors: BELK JAMES M. , BROWN KENNETH S.
Published: January 2006

We introduce forest diagrams to represent elements of Thompson's group F. These diagrams relate to a certain action of F on the real line in the same way that tree diagrams relate to the standard action of F on the unit interval. Using forest diagrams, we give a conceptually simple length formula for elements of F with respect to the {x0,x1} generating set, and we discuss the construction of minimum-length words for positive elements. Finally, we use forest diagrams and the length formula to examine the structure of the Cayley graph of F.
Stimulatory effect of PYY-(3–36) on gonadotropin secretion is potentiated in fasted rats
Authors: Pinilla L. , Fernández-Fernández R. , Vigo E. , Navarro V. M. , Roa J. , Castellano J. M. , Pineda R. , Tena-Sempere M. , Aguilar E.
Published: January 2006

Development and normal function of the reproductive axis requires a precise degree of body energy stores. Polypeptide YY-(3–36) [PYY-(3–36)] is a gastrointestinal secreted molecule recently shown to be involved in the control of food intake with agonistic activity on neuropeptide Y (NPY) receptor subtypes Y2and Y5. Notably, PYY-(3–36) has been recently demonstrated as putative regulator of gonadotropin secretion in the rat. However, the “reproductive” facet of this factor remains to be fully elucidated. In this context, we report herein our analyses of the influence of the nutritional status on the effects of PYY-(3–36) upon GnRH and gonadotropin secretion. The major findings of our study are 1) the stimulatory effect of central administration of PYY-(3–36) on LH secretion was significantly enhanced after fasting and blocked by a GnRH antagonist; 2) besides central effects, PYY-(3–36) elicited LH and FSH secretion directly at the pituitary level, a response that is also augmented by fasting; 3) PYY-(3–36) inhibited GnRH secretion by hypothalamic fragments from male rats fed ad libitum, whereas a significant stimulatory effect was observed after fasting; and 4) the increase in the gonadotropin responsiveness to PYY-(3–36) in fasting was not associated with changes in the expression of Y2and Y5receptor genes at hypothalamus and/or pituitary. In conclusion, our study extends our previous observations suggesting a relevant, mostly stimulatory, role of PYY-(3–36) in the control of gonadotropin secretion. Strikingly, such an effect was significantly enhanced by fasting. Considering the proposed decrease in PYY-(3–36) levels after fasting, the possibility that reduced PYY-(3–36) secretion might contribute to defective function of the gonadotropic axis after food deprivation merits further investigation.
Transcriptional profiling of reporter genes used for molecular imaging of embryonic stem cell transplantation
Authors: Wu Joseph C. , Spin Joshua M. , Cao Feng , Lin Shuan , Xie Xiaoyan , Gheysens Olivier , Chen Ian Y. , Sheikh Ahmad Y. , Robbins Robert C. , Tsalenko Anya , Gambhir Sanjiv S. , Quertermous Tom
Published: January 2006

Stem cell therapy offers exciting promise for treatment of ischemic heart disease. Recent advances in molecular imaging techniques now allow investigators to monitor cell fate noninvasively and repetitively. Here we examine the effects of a triple-fusion reporter gene on embryonic stem (ES) cell transcriptional profiles. Murine ES cells were stably transfected with a self-inactivating lentiviral vector carrying a triple-fusion (TF) construct consisting of fluorescence, bioluminescence, and positron emission tomography (PET) reporter genes. Fluorescence-activated cell sorting (FACS) analysis allowed isolation of stably transfected populations. Microarray studies comparing gene expression in nontransduced control ES cells vs. stably transduced ES cells expressing triple fusion (ES-TF) revealed some increases in transcriptional variability. Annotation analysis showed that ES-TF cells downregulated cell cycling, cell death, and protein and nucleic acid metabolism genes while upregulating homeostatic and anti-apoptosis genes. Despite these transcriptional changes, expression of the TF reporter gene had no significant effects on ES cell viability, proliferation, and differentiation capability. Importantly, transplantation studies in murine myocardium demonstrated the feasibility of tracking ES-TF cells in living subjects using bioluminescence and PET imaging. Taken together, this is the first study to analyze in detail the effects of reporter genes on molecular imaging of ES cells.
Clonidine for the Treatment of Supine Hypertension and Pressure Natriuresis in Autonomic Failure
Authors: Shibao Cyndya , Gamboa Alfredo , Abraham Robert , Raj Satish R. , Diedrich Andre , Black Bonnie , Robertson David , Biaggioni Italo
Published: January 2006

Patients with autonomic failure are disabled by orthostatic hypotension, which can be worsened by the nighttime pressure natriuresis induced by associated supine hypertension. Several pharmacological agents are available that effectively reduce nighttime hypertension, but none of them prevent pressure natriuresis. Because hypertension of autonomic failure can be driven by residual sympathetic tone, we hypothesized that clonidine would be effective in reducing blood pressure (BP) and nocturnal natriuresis. Therefore, we determined the effect of placebo, 0.1 mg clonidine, and 0.1-mg/h nitroglycerin transdermal patch on supine BP, orthostatic hypotension, and pressure natriuresis in 23 patients with primary autonomic failure and supine hypertension. Medications were given at 8:00
pm
, and BP was recorded every 2 hours for 12 hours. The maximal decrease in BP was seen 6 to 8 hours after drug administration and was similar to clonidine and nitroglycerin (−29±9 and −30±10 mm Hg, respectively), as was the average fall in BP throughout the night. However, only clonidine effectively reduced nocturnal natriuresis (−0.09 mmol/mg Cr; 95% CI, −0.13 to −0.04;
P
=0.004), but this was not associated with improvement in morning orthostatic hypotension because of a residual hypotensive effect. The decrease in BP induced by clonidine was modestly but significantly correlated with the magnitude of residual sympathetic tone determined in 10 subjects by the fall in BP induced by ganglionic blockade (
r
=0.66;
P
=0.043). These results are consistent with residual sympathetic tone contributing to supine hypertension in autonomic failure, which can be targeted with clonidine to decrease BP and nocturnal natriuresis.
RNA Silencing In Vivo Reveals Role of p22

phox

in Rat Angiotensin Slow Pressor Response
Authors: Modlinger Paul , Chabrashvili Tinatin , Gill Pritomhinder S. , Mendonca Margarida , Harrison David G. , Griendling Kathy K. , Li Min , Raggio Julie , Wellstein Anton , Chen Yifan , Welch William J. , Wilcox Christopher S.
Published: January 2006

The angiotensin II (Ang II) slow-pressor response entails an increase in mean arterial pressure and reactive oxygen species. We used double-stranded interfering RNAs (siRNAs) in Sprague Dawley rats in vivo to test the hypothesis that an increase in the p22

phox

component of NADPH oxidase is required for this response. Reactive oxygen species were assessed from excretion of 8-isoprostane prostaglandin F
2α
and blood pressure by telemetry. Two siRNA sequences to p22

phox

(sip22

phox

) reduced mRNA >85% in cultured vascular smooth muscle cells. Rats received rapid (10 second) IV injections (50 to 100 μg) of 1 of 2 different sip22

phox

, control siRNA, or vehicle (TransIt in saline) during 14 day SC infusions of Ang II (200 ng · kg
−1
· min
−1
) or sham infusions. In both groups, sip22

phox

, relative to control siRNA, led to significant (
P
<0.001; ≈50%) reductions in expression of p22

phox

mRNA and protein and of NADPH oxidase activity in the kidney cortex. In Ang II–infused rats, sip22

phox

decreased protein expression for Nox-1, -2, and -4 but increased p47

phox

. Three days after sip22

phox

, conscious rats infused with Ang II had a reduced excretion of 8-isoprostane (10±1 versus 19±2 pg · 24 h
−1
;
P
<0.01) and a reduced mean arterial pressure (142±5 versus 168±4 mm Hg;
P
<0.005). An increase in p22

phox

is required for increased renal NADPH oxidase activity, expression of Nox proteins and oxidative stress, and contributes ≤50% to hypertension during an Ang II slow-pressor response.