bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of cell morphology and adhesion by the tuberous sclerosis complex (TSC1/2) gene products in human kidney epithelial cells through increased E‐cadherin/β‐catenin activity
Authors: Li Shaowei , Braverman Richard , Li Hongzhen , Vass William C. , Lowy Douglas R. , DeClue Jeffrey E. 
Published: May 2003

AbstractWe investigated the effects of overexpression of the tuberous sclerosis‐1 and ‐2 (TSC1/2) gene products (hamartin and tuberin, respectively) in the human kidney epithelial cell line 293 with an inducible expression system. As we had observed previously in fibroblasts, 293 cells overexpressing hamartin and/or tuberin grew more slowly in vitro. However, here we also observed that the 293 overexpressing cells underwent a dramatic morphological change in which groups of cells formed compact clusters. The overexpressing cells also displayed decreased dissociation and increased reaggregation in vitro. These changes were found to be associated with an increased level of E‐cadherin, which is known to regulate cell‐cell interactions in epithelial cells, and of its binding partner β‐catenin. Consistent with the role of E‐cadherin in these effects, we found that the observed changes in 293 cell morphology, dissociation, and adhesion were calcium‐dependent, and were reproduced by overexpression of E‐cadherin. In contrast, overexpression of TSC1 in rat embryo fibroblasts, which lack E‐cadherin, failed to elicit the same changes as in 293 cells. We conclude that the hamartin/tuberin complex exerted a direct effect on the morphology and adhesive properties of 293 cells through regulation of the level and/or activity of cellular E‐cadherin/β‐catenin. © 2003 Wiley‐Liss, Inc.
Modulation of the angiogenesis response through Ha‐ras control, placenta growth factor, and angiopoietin expression in mouse skin carcinogenesis
Authors: Larcher Fernando , Franco Marcela , Bolontrade Marcela , Rodriguez‐Puebla Marcelo , Casanova Llanos , Navarro Manuel , Yancopoulos George , Jorcano José L , Conti Claudio J. 
Published: May 2003

AbstractTumor angiogenesis is governed by a complex balance of positive and negative angiogenic factors. Development of chemically‐induced mouse skin tumors appears to be highly dependent on an early burst of neovascularization. We have previously shown that Ha‐ras–driven vascular endothelial growth factor (VEGF) expression plays a pivotal role in this process. However, the status of other critical positive and negative angiogenic factors throughout skin tumorigenesis has not been studied to the same extent. In the present study, we show that another VEGF family member, placenta growth factor (PlGF), was highly upregulated at all tumor stages in a ras‐dependent manner. The study of angiopoietin‐1 (Ang‐1) and angiopoietin‐2 (Ang‐2), ligands of receptor tyrosine kinase 2 (Tie‐2), showed that while stroma–derived Ang‐2 was increased, epidermal Ang‐1 expression was completely abolished at early papilloma formation. Studies using epidermal tumor cell lines suggest that the disappearance of Ang‐1 also depends on ras activation, extending the plethora of events controlled by this oncogene in mouse skin carcinogenesis. Our results indicated that tumor development occurred in a strong angiogenesis‐prone scenario in which PlGF and Ang‐2 acted cooperatively with VEGF, whereas the negative or stabilizing effect of Ang‐1 was abrogated. A time‐course sequence of expression of angiogenic factors expressed throughout tumor growth, as well as the identification of key signaling molecules triggering the angiogenic response, may contribute to the development and testing of antiangiogenic therapeutic strategies with this in vivo tumor model. © 2003 Wiley‐Liss, Inc.
Mutation analysis of CDP, TP53, and KRAS in uterine leiomyomas
Authors: Patrikis Maria I. , Bryan Emma J. , Thomas Nicola A. , Rice Greg E. , Quinn Michael A. , Baker Mark S. , Campbell Ian G. 
Published: May 2003

AbstractLeiomyomas are the most common gynecologic tumors in women, but very little is known about their molecular pathology. We used single‐stranded conformational polymorphism/heteroduplex analysis to analyze 42 unselected uterine leiomyomas for somatic mutations in all coding exons of the gene encoding CCAAT displacement protein (CDP), as well as exons 5–8 of TP53 and codons 1–36 and 38–80 of KRAS. No somatic mutations were identified in either TP53 or KRAS, indicating that disregulation of these genes is not required for leiomyomas development. Aberrant band shifts were identified in CDP, but these were all germline nonpathogenic variants that have been reported previously. There is good functional and genetic evidence indicating that CDP is a leiomyoma suppressor, but our data suggested that somatic mutations in this gene were rare in unselected uterine leiomyomas. It is possible that CDP belongs to a class of tumor suppressor in which loss of only one copy of the gene, either by genetic or epigenetic mechanisms, is sufficient to allow tumor growth. © 2003 Wiley‐Liss, Inc.
Formation of an active form of the interleukin‐2/15 receptor β‐chain by insertion of the intracisternal A particle in a radiation‐induced mouse thymic lymphoma and its role in tumorigenesis
Authors: Ukai Hideki , Ishii‐Oba Hiroko , Ukai‐Tadenuma Maki , Ogiu Toshiaki , Tsuji Hideo 
Published: May 2003

AbstractAlthough many reports suggest that aberrant regulation of cytokine signaling pathways via the interleukin‐2 receptor (IL‐2R) induces tumorigenic transformation, constitutively active IL‐2R in tumors has not been reported. We searched for genomic alteration of the IL‐2/15R β‐subunit gene (IL‐2/15Rβ) in cytokine‐independent cell lines established from radiation‐induced mouse thymic lymphomas. In the TL34 cell line and its primary tumor, one of the IL‐2/15Rβ alleles was rearranged by the insertion of an intracisternal A particle (IAP) retrotransposon. The IAP‐IL2/15Rβ chimeric gene expressed chimeric mRNA in which IAP‐coding Gag‐Pol mRNA was fused to IL‐2/15Rβ mRNA and coded for Gag‐Pol‐IL‐2/15Rβ chimeric protein. Forced expression of the Gag‐Pol‐IL‐2/15Rβ chimeric cDNA in a mouse cytotoxic T‐cell line (CTLL‐2) converted IL‐2‐dependent cell growth to IL‐2‐independent growth, suggesting that the chimeric protein activates some of the IL‐2 signaling pathways necessary for cell proliferation. Downregulation of the expression of the Gag‐Pol‐IL‐2/15Rβ chimeric protein in TL34 by antisense RNA inhibited cell growth, and concomitantly reduced the level of c‐myc protein. These results suggest that the Gag‐Pol‐IL‐2/15Rβ is a constitutively active form that transmits proliferative signals by expressing downstream target genes, including c‐myc. Thus, we demonstrated that the chimeric receptor gene produced by the insertion of an IAP functions as an oncogene by providing IL‐2‐independent autonomous growth potential. © 2003 Wiley‐Liss, Inc.
MRI‐guided focused ultrasound surgery in the brain: Tests in a primate model
Authors: McDannold Nathan , Moss Mark , Killiany Ron , Rosene Douglas L. , King Randy L. , Jolesz Ferenc A. , Hynynen Kullervo 
Published: May 2003

AbstractMRI‐guided focused ultrasound was tested in the brains of rhesus monkeys. Locations up to 4.8 cm deep were targeted. Focal heating was observed in all cases with MRI‐derived temperature imaging. Subthreshold heating was observed at the focus when the ultrasound beam was targeted with low power sonications, and in the ultrasound beam path during high‐power exposures. Lethal temperature values and histologically confirmed tissue damage were confined to the focal zone (e.g., not in the ultrasound beam path), except when the focus was close to the bone. In that case, damage to the neighboring brain tissue was observed. Focal lesions were observed on histological examination and, in some cases, in MR images acquired immediately after the ultrasound exposures. The capabilities demonstrated in this study will be of benefit for clinical ultrasound therapies in the brain. Magn Reson Med 49:1188–1191, 2003. © 2003 Wiley‐Liss, Inc.
Increased diffusion sensitivity with hyperechos
Authors: Frank Lawrence R. , Wong Eric C. , Liu Thomas T. , Buxton Richard B. 
Published: May 2003

AbstractIt is shown that the introduction of a 180° refocusing pulse into a standard diffusion weighted stimulated echo sequence is equivalent to the simplest hyperecho sequence with identical diffusion weighting but equal or greater signal‐to‐noise (SNR) and thus equal or greater diffusion contrast. For high b‐value imaging, the hyperecho sequence thus possesses the high diffusion contrast in the presence of small T1/T2 ratios characteristic of stimulated echo sequences but with less than the 50% loss in SNR that is associated with the stimulated echo. For low b‐value imaging, the hyperecho signal converges to that of the standard spin echo. The advantages of the two‐pulse diffusion weighted hyperecho sequence are demonstrated theoretically. Experimental results are shown in the application to high angular resolution diffusion encoding (HARD) in normal human brain. Magn Reson Med 49:1098–1105, 2003. Published 2003 Wiley‐Liss, Inc.
Magnetic resonance imaging of gastric cancer in Tff1 knock‐out mice
Authors: Berr Stuart S. , Roche James K. , El‐Rifai Wa'el , Smith Michael F. , Powell Steven M. 
Published: May 2003

AbstractIn this work, the use of MRI to stage gastric neoplasia in a mouse model of spontaneous gastric cancer is demonstrated. The methodology involves 1) the use of deuterated water (2H2O) to distend the stomach, and to provide negative contrast between the stomach and the lumen without inducing susceptibility‐based field shifts; 2) GlucaGen® to minimize motion artifacts that arise from peristalsis; and 3) Gd‐DTPA to enhance contrast between the dysplasia/tumor and the normal wall. Initial images are presented from a Tff1 −/− homozygous knock‐out model of gastric cancer and a heterozygous C57BL6/J control mouse. There are clear differences between the two types of animals in the MR appearance of the stomach. The distended stomach of the control mouse has a smooth perimeter and a thin wall, and an absence of nodules. The stomach of the Tff1 −/− mouse demonstrates a thickened wall; a jagged, irregular surface; and protruding nodules that are bright after injection of Gd‐DTPA. Magn Reson Med 49:1033–1036, 2003. © 2003 Wiley‐Liss, Inc.
Image‐based tracking of optically detunable parallel resonant circuits
Authors: Eggers Holger , Weiss Steffen , Boernert Peter , Boesiger Peter 
Published: May 2003

AbstractIn this work strategies for the robust localization of parallel resonant circuits are investigated. These strategies are based on the subtraction of two images, which ideally differ in signal intensity at the positions of the devices only. To modulate their signal amplification, and thereby generate the local variations, the parallel resonant circuits are alternately detuned and retuned during the acquisition. The integration of photodiodes into the devices permits their fast optical switching. Radial and spiral imaging sequences are modified to provide the data for the two images in addition to those for a conventional image in the same acquisition time. The strategies were evaluated by phantom experiments with stationary and moving catheter‐borne devices. In particular, rapid detuning and retuning during the sampling of single profiles is shown to lead to a robust localization. Moreover, this strategy eliminates most of the drawbacks usually associated with image‐based tracking, such as low temporal resolution. Image‐based tracking may thus become a competitive (if not superior) alternative to projection‐based tracking of parallel resonant circuits. Magn Reson Med 49:1163–1174, 2003. © 2003 Wiley‐Liss, Inc.
Improved preparation of chick embryonic samples for magnetic resonance microscopy
Authors: Zhang Xiaowei , Yelbuz T. Mesud , Cofer Gary P. , Choma Michael A. , Kirby Margaret L. , Johnson G. Allan 
Published: May 2003

AbstractPrevious work demonstrated the power of three‐dimensional (3D) magnetic resonance microscopy (MRM) to follow complicated morphologic development in the embryonic cardiovascular system. In this study we describe a new dual‐contrast method for specimen preparation that combines perfusion fixation and immersion in fixative with macro‐ and small molecular gadolinium agents to provide enhanced definition of both the heart wall and chamber. MRM was performed at 9.4 T with image resolutions of 25, 31, and 50 μm isotropic voxels for three stages of chick embryos (day 4, day 5.5, and day 9), and compared to histological sections of the same embryos. The results show considerable improvement of image quality over previous efforts, with better signal‐to‐noise ratio (SNR) and contrast between the cardiac chamber and myocardial wall. Excellent correlation was shown between the MRM images and histological sections. Thus, 3D high‐resolution MRM in combination with the dual‐contrast technique is useful for acquiring quantitative 3D morphologic data regarding heart development. Magn Reson Med 49:1192–1195, 2003. © 2003 Wiley‐Liss, Inc.
Measuring the arterial input function with gradient echo sequences
Authors: van Osch Matthias J.P. , Vonken Evert‐jan P.A. , Viergever Max A. , van der Grond Jeroen , Bakker Chris J.G. 
Published: May 2003

AbstractThe measurement of the arterial input function by use of gradient echo sequences was investigated by in vitro and in vivo experiments. First, calibration curves representing the influence of the concentration of Gd‐DTPA on both the phase and the amplitude of the MR signal were measured in human blood by means of a slow‐infusion experiment. The results showed a linear increase in the phase velocity and a quadratic increase in ΔR as a function of the Gd‐DTPA concentration. Next, the resultant calibration curves were incorporated in a partial volume correction algorithm for the arterial input function determination. The algorithm was tested in a phantom experiment and was found to substantially improve the accuracy of the concentration measurement. Finally, the reproducibility of the arterial input function measurement was estimated in 16 patients by considering the input function of the left and the right sides as replicate measurements. This in vivo study showed that the reproducibility of the arterial input function determination using gradient echo sequences is improved by employing a partial volume correction algorithm based on the calibration curve for the contrast agent used. Magn Reson Med 49:1067–1076, 2003. © 2003 Wiley‐Liss, Inc.
Sensitive CEST agents based on nucleic acid imino proton exchange: Detection of poly(rU) and of a dendrimer‐poly(rU) model for nucleic acid delivery and pharmacology
Authors: Snoussi Karim , Bulte Jeff W.M. , Guéron Maurice , van Zijl Peter C.M. 
Published: May 2003

AbstractIt is shown that the exchange properties of the imino and hydroxyl protons of polyuridilic acid (poly(rU)) allow use of this compound as a chemical‐exchange saturation transfer (CEST) contrast agent. A proton/proton sensitivity enhancement factor of over 5000 per imino proton allowed the detection of a few micromolar of polymer (2000 uridine units; 644 kD) with a 50% change in the water signal. The enhancement factor would increase further at even lower concentrations, opening up the submicromolar range. When poly(rU) was complexed to a dendrimer carrying 250 positive charges, the stoichiometry was approximately one RNA for 10 dendrimers. The sensitivity enhancement was reduced but remained large (2300/imino proton), bringing enhanced CEST visibility to the dendrimers. The net charge of the complex was positive, suggesting that the complexed dendrimers would still interact with cell membranes, and that the RNA‐dendrimer complex could provide a model for a gene delivery system with good CEST visibility. Magn Reson Med 49:998–1005, 2003. © 2003 Wiley‐Liss, Inc.
B1AC‐MAMBA:B1array combined with multiple‐acquisition microB0array parallel magnetic resonance imaging
Authors: Paley Martyn N.J. , Lee Kuan J. , Wild James M. , Fichele Stanislao , Whitby Elspeth H. , Wilkinson Iain D. , Van Beek Edwin J. , Griffiths Paul D. 
Published: May 2003

AbstractThe combination of an in‐planeB1sensitivity encoding (SENSE) technique with a simultaneous multiple‐sliceB0field step technique (multiple‐acquisition microB0array (MAMBA)) has produced high scan time reduction factors (R ≤ 8). In this study, two slices were acquired simultaneously in combination with ×2 and ×4 SENSE in‐plane encoding using a MAMBA steppedB0field coil inside a four‐channel phased‐array coil system. Experiments were performed on a 1.5 T Infinion system (Philips Medical Systems, Cleveland, OH). The signal‐to‐noise ratio (SNR) was reduced with higher R factors, as was expected from the reduced number of acquisitions used to create the unaliased images. The combination of SENSE and MAMBA offers great promise for reducing scan times through parallel acquisition while at the same time reducing the number of RF channels required by a factor equal to the number of field steps employed. TheB1array combined with MAMBA (B1AC‐MAMBA) technique is applicable when the length of an object is much greater than its diameter, as in scanning limbs or in whole‐body screening for disease. Magn Reson Med 49:1196–1200, 2003. © 2003 Wiley‐Liss, Inc.
Receptor‐mediated endocytosis of iron‐oxide particles provides efficient labeling of dendritic cells for in vivo MR imaging
Authors: Ahrens E.T. , Feili‐Hariri M. , Xu H. , Genove G. , Morel P.A. 
Published: May 2003

AbstractDendritic cells (DCs) function as antigen presenting cells in vivo and play a fundamental role in numerous diseases. New methods are described for high‐efficiency intracellular labeling of DCs with superparamagnetic iron‐oxide (SPIO) utilizing a receptor‐mediated endocytosis (RME) mechanism. Bone marrow‐derived DCs or a fetal skin‐derived DC line were incubated with SPIO conjugated to anti‐CD11c monoclonal antibody (mAb) under conditions favoring RME. These cells exhibited approximately a 50‐fold increase in uptake relative to DCs incubated with SPIO without the mAb. Flow cytometry studies assaying cell surface markers showed a down‐modulation of CD11c, but no other changes in phenotype. Immunological function of the DCs was unmodified by the labeling, as determined by cytokine secretion assays. The RME mechanism was confirmed using electron microscopy, endocytosis inhibition assays, and incubation experiments with SPIO conjugated to mAbs against accessory molecules that are not expressed on DCs. Labeled DCs were injected into murine quadriceps and monitored in vivo for several days using MR microimaging at 11.7 T. DCs were observed to remain within the muscle for >24 hr. The use of RME is an efficient way to label immune cells for in vivo MRI and can be applied to a wide variety of cell types. Magn Reson Med 49:1006–1013, 2003. © 2003 Wiley‐Liss, Inc.
In vivo assessment of macromolecular content in articular cartilage of the goat knee
Authors: Laurent Didier , Wasvary James , Rudin Markus , O'Byrne Elizabeth , Pellas Theodore 
Published: May 2003

AbstractLoss of proteoglycans (PGs) from the extracellular matrix of cartilage is an early event of osteoarthritis. The capability of Gd(DTPA)2–‐enhanced MRI to quantitatively assess PG content was explored in a goat model of cartilage degeneration. Partial to total PG depletion was induced by an intraarticular injection of papain 1 day prior to the MRI session. A close correlation was found between the extent of the PG loss and the Gd(DTPA)2–‐induced T1 decrease. Papain‐induced PG depletion was confirmed by post‐mortem histological and biochemical assessments. A 2‐hr delay after Gd(DTPA)2– injection was found to be optimal for an accurate quantitation of the cartilage defect. A series of knee flexions were performed post‐Gd(DTPA)2– injection to facilitate penetration of the contrast agent into cartilage. However, ΔT1's observed in cartilage of exercised goat knees were not affected by papain or IL1β pretreatment. Therefore, as long as a preinjection T1 map was obtained, the Gd(DTPA)2–‐enhanced MRI technique provided good sensitivity in detecting partial loss of PG in articular cartilage. This was true only when the animal was maintained in a resting state during diffusion of the Gd(DTPA)2–. This approach is of particular interest for long‐term evaluations of cartilage degeneration and regeneration. Magn Reson Med 49:1037–1046, 2003. © 2003 Wiley‐Liss, Inc.
Optimized spiral imaging for measurement of myocardial T2 relaxation
Authors: Foltz Warren D. , Al‐Kwifi Osama , Sussman Marshall S. , Stainsby Jeff A. , Wright Graham A. 
Published: May 2003

AbstractMicrocirculation oxygen levels and blood volumes should be reflected in measurements of myocardial T2 relaxation. This work describes the optimization of a spiral imaging strategy for robust myocardial T2 measurement to minimize the standard deviation of T2 measurement (σT2). Theoretical and experimental studies of blurring at muscle/blood interfaces enabled the derivation of parameter sets which reduce σ T2 to the level of 5%. T2 relaxation mapping within healthy volunteers provided estimation of residual σT2 within the optimized technique. The standard deviation in T2 measurement across regions of interest (ROIs) in different locations is about 9%. The standard deviation in T2 measurement in an ROI across different time points is about 5%. Magn Reson Med 49:1089–1097, 2003. © 2003 Wiley‐Liss, Inc.
Cluster analysis of BOLD fMRI time series in tumors to study the heterogeneity of hemodynamic response to treatment
Authors: Baudelet Christine , Gallez Bernard 
Published: May 2003

AbstractBOLD‐contrast functional MRI (fMRI) has been used to assess the evolution of tumor oxygenation and blood flow after treatment. The aim of this study was to evaluate K‐means‐based cluster analysis as a exploratory, data‐driven method. The advantage of this approach is that it can be used to extract information without the need for prior knowledge concerning the hemodynamic response function. Two data sets were acquired to illustrate different types of BOLD fMRI response inside tumors: the first set following a respiratory challenge with carbogen, and the second after pharmacological modulation of tumor blood flow using flunarizine. To improve the efficiency of the clustering, a power density spectrum analysis was first used to isolate voxels for which signal changes did not originate from noise or linear drift. The technique presented here can be used to assess hemodynamic response to treatment, and especially to display areas of the tumor with heterogeneous responses. Magn Reson Med 49:985–990, 2003. © 2003 Wiley‐Liss, Inc.
Novel ROC‐type method for testing the efficiency of multivariate statistical methods in fMRI
Authors: Nandy Rajesh R. , Cordes Dietmar 
Published: May 2003

AbstractThe receiver operating characteristic (ROC) method is a useful and popular tool for testing the efficiency of various diagnostic tests applicable to functional MRI (fMRI) data. Typically, the diagnostic tests are applied on simulated and pseudo‐human fMRI data, and the area under the ROC curve is used as a measure of the efficiency of the diagnostic test. The effectiveness of such a method depends on how well the simulated data approximate the real data. For multivariate statistical methods, however, this technique is usually inadequate, as the spatial dependence among voxels is ignored for simulated data. In this work a modified ROC method using real fMRI data with a broader scope is proposed. This method can be applied to most fMRI postprocessing techniques, including multivariate analyses such as canonical correlation analysis (CCA). Also, the relationship of the modified ROC method with the conventional ROC method is discussed in detail. Magn Reson Med 49:1152–1162, 2003. © 2003 Wiley‐Liss, Inc.