bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tnfa and Il‐10 deficiencies have contrasting effects on lung tumor susceptibility: Gender‐dependent modulation of IL‐10 haploinsufficiency
Authors: Bernert Heike , Sekikawa Kenji , Radcliffe Richard A. , Iraqi Fuad , You Ming , Malkinson Alvin M. 
Published: October 2003

AbstractEpidemiologic evidence suggests that pulmonary diseases with a prominent chronic inflammatory component elevate lung cancer risk. Genetic manipulations of mouse models of lung inflammation and tumorigenesis can be used to investigate this association. The genes encoding pro‐inflammatory tumor necrosis factor‐α (TNFα) and antiinflammatory IL‐10 cytokines map within quantitative trait loci that regulate susceptibility to lung tumor development in mice; sensitive A/J and resistant C57BL/6J (B6) mice have different Tnfa and Il‐10 alleles. Genetic ablation studies were performed to examine whether these genes would qualify as candidate tumor modifiers. Tnfa null (−/−) mice on a B6 background and B6.129 Il‐10−/− mice were intercrossed with A/J mice and subjected to urethane carcinogenesis; lung tumor multiplicity was determined 20 weeks later. In the absence of one copy of Tnfa, tumor number. Male Il‐10+/+ mice developed more tumors than did female mice (P < 0.001), absence of one copy of Il‐10 raised tumor number in female mice to that observed in +/+ males, but no change in multiplicity occurred in Il‐10 hemizygous males. Thus, a deficit of pro‐inflammatory TNFα decreased the number of tumors, whereas diminished gene copy number of anti‐inflammatory IL‐10 increased tumorigenesis; manifestation of an effect of Il‐10 haploinsufficiency is gender dependent. These studies support a role for inflammation in lung cancer susceptibility. © 2003 Wiley‐Liss, Inc.
Changes in gene expression during chemical‐induced nephrocarcinogenicity in the Eker rat
Authors: Patel Sonal K. , Ma Ning , Monks Terrence J. , Lau Serrine S. 
Published: October 2003

AbstractHydroquinone (HQ) is a rodent carcinogen and a potential human carcinogen. Glutathione conjugation of HQ enhances its biological reactivity, and 2,3,5‐tris‐(glutathion‐S‐yl)hydroquinone (TGHQ) is a potent nephrotoxicant and nephrocarcinogen in the Eker rat. Moreover, a single exposure of primary epithelial cells derived from Eker rat kidneys to TGHQ transforms these cells into an immortalized phenotype (quinol‐thioether transformed rat renal epithelial (QT‐RRE) cells). The Eker rat bears a mutation in one allele of the tuberous sclerosis‐2 (Tsc‐2) tumor suppressor gene, which predisposes the animals to the development of spontaneous and chemical‐induced renal cell carcinoma. Thus, the Eker rat provides a unique model for elucidating the mechanisms of renal tubular epithelial carcinogeneisis. cDNA microarray analysis of QT‐RRE3 cells and of tumor tissue derived from the kidneys of Eker rats treated with TGHQ revealed alterations (by threefold or greater) in the expression of a total of 80 genes. Fifteen percent of these genes exhibited similar expression patterns in both QT‐RRE cells and tumor tissue. The differentially expressed genes primarily participate in three major areas: (1) signal transduction or in the regulation of signal transduction (extracellular signal regulated kinase 2 (ERK2); protein kinase CK2; protein kinase B; c‐jun; NF‐κB; ras‐related GTPases; annexins), (2) stress response, tissue remodeling, and DNA repair (glutathione‐S‐transferases; procollagen c proteinase enhancer; plasminogen activator; tissue inhibitor of metalloprotease 3; apurinic/apyrimidic endonuclease), and (3) electron transport and energy homeostasis (cytochrome c oxidase subunits). The changes in the expression of many of these genes was confirmed by reverse transcription (RT)‐polymerase chain reactions (PCR) using primers specific for the differentially expressed genes. As an example, the annexin I and II genes, implicated in signal transduction, were highly induced in tumor tissue and also in dysplastic lesions isolated from the kidneys of rats treated chronically with TGHQ. The annexin I and II proteins were also upregulated in tumor tissue, which probably play an important role in TGHQ‐induced nephrocarcinogenesis. Moreover, in the present study, a tumorigenicity assay using athymic nude mice revealed that QT‐RRE cell lines formed tumors when injected in the subcutis of nude mice, providing evidence that the cells are malignantly transformed. Histopathological analysis further indicated that the tumors were composed of neoplastic cells, resembling renal carcinoma cells with varying degrees of atypia, with the presence of apoptotic and mitotic figures. © 2003 Wiley‐Liss, Inc.
Elevated levels of prostate‐specific antigen (PSA) in prostate cancer cells expressing mutant p53 is associated with tumor metastasis
Authors: Downing Sean , Bumak Clare , Nixdorf Sheri , Ow Kim , Russell Pamela , Jackson Paul 
Published: October 2003

AbstractThe underlying basis for rising levels of prostate‐specific antigen (PSA) in prostate cancer is not fully understood, but attention has turned to the possibility that loss of normal p53 function might be directly involved. We have investigated the relationship between p53 function and PSA expression using in vitro and in vivo approaches. Three prostate cancer–derived p53 mutants (F134L, M237L, R273H) were introduced into LNCaP prostate cancer cells and stable transfectants established. Expression of mutant p53 was demonstrated by Western blot analysis, inactivation of wtp53 function, and a loss of p53‐dependent responses to DNA damage induced by UV‐irradiation and cisplatin. Levels of PSA mRNA and secreted protein were determined by RT‐PCR and Western blotting, respectively. Serine protease activity was assessed using an esterase assay. In vivo effects of mutant p53 expression were examined after orthotopic implantation into prostates of nude mice. Expression of all p53 mutants was associated with elevated PSA mRNA and secreted PSA protein. In a representative line, mutant p53 was also associated with increased PSA protease‐like activity compared with a control line expressing wildtype p53. Overall PSA levels, and PSA levels in serum from mice bearing tumors derived from cells expressing mutant p53, were increased compared with levels in mice bearing tumors derived from control cells. In addition, the tumors derived from cells with mutant p53 had increased vascularization and induced lymph node metastases. These data provide in vitro and in vivo support for the notion that p53 mutations directly contribute to increased levels of serum PSA, and are associated with more aggressive tumors. © 2003 Wiley‐Liss, Inc.
Generalized diffusion tensor imaging and analytical relationships between diffusion tensor imaging and high angular resolution diffusion imaging
Authors: Özarslan Evren , Mareci Thomas H. 
Published: October 2003

AbstractA new method for mapping diffusivity profiles in tissue is presented. The Bloch‐Torrey equation is modified to include a diffusion term with an arbitrary rank Cartesian tensor. This equation is solved to give the expression for the generalized Stejskal‐Tanner formula quantifying diffusive attenuation in complicated geometries. This makes it possible to calculate the components of higher‐rank tensors without using the computationally‐difficult spherical harmonic transform. General theoretical relations between the diffusion tensor (DT) components measured by traditional (rank‐2) DT imaging (DTI) and 3D distribution of diffusivities, as measured by high angular resolution diffusion imaging (HARDI) methods, are derived. Also, the spherical tensor components from HARDI are related to the rank‐2 DT. The relationships between higher‐ and lower‐rank Cartesian DTs are also presented. The inadequacy of the traditional rank‐2 tensor model is demonstrated with simulations, and the method is applied to excised rat brain data collected in a spin‐echo HARDI experiment. Magn Reson Med 50:955–965, 2003. © 2003 Wiley‐Liss, Inc.
Value of a blood pool contrast agent in MR venography of the lower extremities and pelvis: Preliminary results in 12 patients
Authors: Aschauer Manuela , Deutschmann Hannes A. , Stollberger Rudolf , Hausegger Klaus A. , Obernosterer Andrea , Schöllnast Helmut , Ebner Franz 
Published: October 2003

AbstractThe purpose of this study was to determine the value of a blood‐pool contrast media (NC100150, Nycomed Imaging (now Amersham Health) Oslo, Norway) for evaluation of venous thrombosis of the deep veins of the pelvis and lower extremities. Twelve patients were prospectively evaluated with conventional X‐ray venography (XRV) and MR venography (MRV) after injection of NC100150 (2 ml/kg body weight). The source images and 3D maximum intensity projection (MIP) were viewed on an independent workstation. Diagnosis was made in consensus from two radiologists. Diagnostic image quality was achieved in 87 veins with XRV and MRV. As determined by XRV, thrombus was present in 30 out of 87 veins (34.5%). There was agreement concerning absence or presence of thrombi in 83 out of 87 veins (95.4%; κ = 0.9 ± 0.05). Compared to XRV, overall sensitivity and specificity of blood‐pool MRV were 93.3% and 96.5%, respectively. Two venous thromboses of the popliteal and posterior tibial vein were diagnosed in MRV, but not in XRV. Conversely, two venous thromboses below the knee had been missed by MRV. NC100150 allows prolonged and improved visualization of the peripheral vasculature and may overcome some limitations of gadolinium contrast media. A more complete examination of the proximal venous tree may be possible than with conventional XRV. Arterial and venous enhancement and motion artifacts can limit image interpretation. Magn Reson Med 50:993–1002, 2003. © 2003 Wiley‐Liss, Inc.
Triggered, navigated, multi‐baseline method for proton resonance frequency temperature mapping with respiratory motion
Authors: Vigen Karl K. , Daniel Bruce L. , Pauly John M. , Butts Kim 
Published: October 2003

AbstractA technique is presented for the acquisition of temperature maps in the presence of variable respiratory motion using the proton resonance frequency (PRF) shift. The technique uses respiratory triggering, diaphragm position determination with a navigator echo, and the collection of multiple baseline images to generate temperature maps. Laser ablations were performed in an ex vivo liver phantom undergoing variable simulated respiratory motion and in vivo in four porcine livers, demonstrating a reduction of artifacts in the computed temperature maps compared with conventional single baseline techniques, both uncorrected and corrected for motion. Magn Reson Med 50:1003–1010, 2003. © 2003 Wiley‐Liss, Inc.
Parsing local signal evolution directly from a single‐shot MRI signal: A new approach for fMRI
Authors: Twieg Donald B. 
Published: October 2003

AbstractIn this work a new single‐shot MRI method, single‐shot parameter assessment by retrieval from signal encoding (SS‐PARSE), is introduced. This method abandons a fundamental simplifying assumption that is used in conventional MRI methods. Established MRI methods implicitly assume that the local intrinsic signal does not change its amplitude or phase during signal acquisition, even though these changes may be substantial, especially during the relatively long signals used in single‐shot image acquisitions. SS‐PARSE, on the other hand, acknowledges local decay and phase evolution, and models each signal datum as a sample from (k,t)‐space rather than k‐space. Because of this more accurate signal model, SS‐PARSE promises improved performance in terms of accuracy and robustness, but requires more intensive reconstruction computations. The theoretical properties of the method are discussed, and simulation results are presented that demonstrate more robust and accurate measurements of relaxation rate changes associated with brain activation in functional MRI (fMRI), freedom from geometric errors due to off‐resonance frequencies, and better tolerance of the large susceptibility gradients that occur naturally in parts of the brain. In addition, this technique has the potential to assess nonexponential relaxation behavior during a single‐shot signal. Magn Reson Med 50:1043–1052, 2003. © 2003 Wiley‐Liss, Inc.
Breast tissue differentiation using arterial spin tagging
Authors: Zhu David C. , Buonocore Michael H. 
Published: October 2003

AbstractAn arterial spin tagging (AST) pulse sequence has been developed to measure T1 and relative blood perfusion. This full sequence is composed of three sequences: selective tagging, nonselective tagging, and nontagging. Perfusion quantification error resulting from imperfect inversion and acquisition slice profiles has been addressed in the literature. In this work, the error is reduced through the application of optimized Shinnar‐Le Roux (SLR) RF pulses and a semi‐log linear regression data‐processing technique. A threshold approach based on the breast tissue T1 and relative blood perfusion is introduced to show that these two parameters can be applied to breast tissue differentiation and potentially to cancer detection. Magn Reson Med 50:966–975, 2003. © 2003 Wiley‐Liss, Inc.
High‐resolution diffusion and relaxation‐edited magic angle spinning 1H NMR spectroscopy of intact liver tissue
Authors: Rooney O.M. , Troke J. , Nicholson J.K. , Griffin J.L. 
Published: October 2003

AbstractHigh‐resolution magic angle spinning (HRMAS) 1H NMR spectroscopy is ideal for monitoring the metabolic environment within tissues, particularly when spectra are weighted by physical properties such as T1 and T2 relaxation times and apparent diffusion coefficients (ADCs). In this study, spectral‐editing using T1 and T2 relaxation times and ADCs at variable diffusion times was used in conjunction with HRMAS 1H NMR spectroscopy at 14.1 T in liver tissue. To enhance the sensitivity of ADC measurements to low molecular weight metabolites a T2 spin echo was included in a standard stimulated gradient spin‐echo sequence. Fatty liver induced in rats by chronic orotic acid feeding was investigated using this modified sequence. An increase in the combined ADC for the co‐resonant peaks glucose, betaine, and TMAO during fatty liver disease was detected (ADCs = 0.60 ± 0.11 and 0.35 ± 0.1 * 10−9 m2s−1 (n = 3) for rats fed with and without orotic acid), indicative of a reduction in glucose and betaine and an increase in TMAO. Magn Reson Med 50:925–930, 2003. © 2003 Wiley‐Liss, Inc.
Helical MR: Continuously moving table axial imaging with radial acquisitions
Authors: Shankaranarayanan Ajit , Herfkens Robert , Hargreaves Brian M. , Polzin Jason A. , Santos Juan M. , Brittain Jean H. 
Published: October 2003

AbstractA technique for extended field of view MRI is presented. Similar to helical computed tomography, the method utilizes a continuously moving patient table, a 2D axial slice that remains fixed relative to the MRI magnet, and a radial k‐space trajectory. A fully refocused SSFP acquisition enables spatial resolution comparable to current clinical protocols in scan times that are sufficiently short to allow a reasonable breathhold duration. RF transmission and signal reception are performed using the RF body coil and the images are reconstructed in real time. Experimental results are presented that illustrate the technique's ability to resolve small structures in the table‐motion direction. Simulation experiments to study the steady‐state response of the fully refocused SSFP acquisition during continuous table motion are also presented. Finally, whole body images of healthy volunteers demonstrate the high image quality achieved using the helical MRI approach. Magn Reson Med 50:1053–1060, 2003. © 2003 Wiley‐Liss, Inc.
Variable‐density spiral 3D tailored RF pulses
Authors: Stenger V. Andrew , Boada Fernando E. , Noll Douglas C. 
Published: October 2003

AbstractA variable‐density spiral method is presented for reducing three‐dimensional tailored radiofrequency pulse duration. Pulse length reductions of 21–32% are possible, with only a small error in the desired excitation profile. The method is demonstrated using simulations, phantom experiments, and T2*‐weighted images of brain regions with susceptibility‐induced intravoxel dephasing. Four 19.7‐ms shots were needed to excite a 5‐mm‐thick slice with reduced susceptibility artifacts in the sinus region at 3T. Magn Reson Med 50:1100–1106, 2003. © 2003 Wiley‐Liss, Inc.
Utilization of an intra‐oral diamagnetic passive shim in functional MRI of the inferior frontal cortex
Authors: Wilson James L. , Jezzard Peter 
Published: October 2003

AbstractDue to the presence of gross magnetic susceptibility artifacts, functional MRI (fMRI) has proved problematic in studies of the human inferior frontal cortex (IFC). There is a strong desire, therefore, to employ techniques that mitigate susceptibility artifacts in the IFC while preserving the imaging parameters of an fMRI study. It has been shown that the use of a single, strongly diamagnetic, intra‐oral passive shim significantly improves the homogeneity of the static magnetic field (B0) and, as a result, alleviates the susceptibility artifacts within the IFC. In this study, practical issues regarding the use of an intra‐oral passive shim are examined. We investigated B0 instabilities within the IFC resulting from subject head motion in order to calculate the effects of an intra‐oral passive shim on the temporal variance of an EPI time series. These studies show that the addition of an intra‐oral passive shim improves both B0 homogeneity and signal stability, and increases sensitivity to functional activation. Magn Reson Med 50:1089–1094, 2003. © 2003 Wiley‐Liss, Inc.
Accuracy and reproducibility in phase contrast imaging using SENSE
Authors: Thunberg Per , Karlsson Matts , Wigström Lars 
Published: October 2003

AbstractThe purpose of this study was to evaluate the accuracy and reproducibility of phase contrast imaging using the sensitivity encoding (SENSE) method at different reduction factors. Analytical expressions were derived that state how reproducibility is influenced for velocity and flow measurements. Computer simulations, and in vitro and in vivo studies were performed in order to validate these expressions and to assess how accuracy is affected when different reduction factors are applied. It was shown that reproducibility depends on the reduction and geometry factors. Since the geometry factor varies spatially, so does the reproducibility for phase contrast imaging. In areas with high geometry factors, the standard deviation (SD) may become so large that aliasing occurs. The accuracy of phase contrast imaging is not influenced directly when SENSE is used, but may be indirectly influenced due to high SDs of the measured phase that may subsequently cause aliasing. The current results show that it is possible to achieve accurate flow measurements even at high reduction factors. By taking the geometry factor into account, it may be possible to find areas where phase contrast imaging is accurate even at high reduction factors. Magn Reson Med 50:1061–1068, 2003. © 2003 Wiley‐Liss, Inc.
Modulation of the pharmacokinetics of macromolecular contrast material by avidin chase: MRI, optical, and inductively coupled plasma mass spectrometry tracking of triply labeled albumin
Authors: Dafni Hagit , Gilead Assaf , Nevo Nava , Eilam Raya , Harmelin Alon , Neeman Michal 
Published: October 2003

AbstractThe goal of this work was to develop an MRI method for mapping the clearance of interstitial macromolecular plasma proteins after their extravasation from permeable blood vessels. To that end, a well‐defined window of exposure to elevated blood levels was generated by inducing rapid clearance of macromolecular contrast material from the blood. Experimental removal of the intravascular component allowed subsequent tracking of clearance from the interstitial compartment in the absence of further contrast extravasation. The contrast material was based on albumin triply labeled with biotin, fluorescent tag, and GdDTPA, allowing optical, inductively coupled plasma mass spectrometry (ICP‐MS) and MRI detection. The biotin tag was used here for in vivo chasing of the contrast material from the blood by intravenous administration of avidin. Upon administration of avidin the contrast material disappeared from the blood vessels and was cleared by the liver and spleen as detected by MRI, fluorescence of blood samples and histological sections, and by ICP‐MS. Nonbiotinylated fluorescent albumin was not affected by administration of avidin. Contrast material that extravasated from leaky blood vessels in a VEGF overexpressing tumor, prior to administration of avidin, was not cleared by the addition of avidin and showed continued interstitial convection. Thus, avidin‐chase provides an effective tool for in vivo manipulation of the arterial input function by providing experimental control over the rate of clearance of the contrast material from the circulation. Magn Reson Med 50:904–914, 2003. © 2003 Wiley‐Liss, Inc.
A Cbl:clathrin complex involved in NGF signaling for neurite outgrowth
Authors: Howe Charles L. 
Published: October 2003

AbstractCbl regulates receptor tyrosine kinase activity by promoting the endocytosis of receptors from the plasma membrane. The mechanism of this effect is unclear, but recent evidence suggests that Cbl mediates ubiquitin‐dependent sorting of receptors following recruitment to phosphotyrosine motifs in the activated receptor. Moreover, recent findings support a role for Cbl in the clathrin‐mediated endocytosis of receptor tyrosine kinases. We provide evidence that Cbl is found in complex with clathrin and is localized to clathrin‐coated vesicles following NGF stimulation of TrkA. We also show that overexpression of Cbl enhances clathrin‐mediated endocytosis of 125I‐NFG, and that this increased internalization is correlated with a substantial acceleration of neurite outgrowth in response to NGF. Our data suggest that Cbl may participate in the formation of a multi‐protein complex involved in the clathrin‐mediated endocytosis of receptor tyrosine kinases, and that Cbl may function as a positive regulator of such kinases in specific cellular contexts.
Time dependence of the effect of ethanol on serotonin synthesis and tryptophan hydroxylase expression in the dorsal and median raphe of young rats
Authors: Jang Mi‐Hyeon , Shin Min‐Chul , Kim Hong , Kim Ee‐Hwa , Kim Chang‐Ju 
Published: October 2003

AbstractSerotonin (5‐hydroxytryptamine, 5‐HT) has been implicated in the pathophysiology of many neuropsychiatric disorders, and alcohol is reported to influence serotonergic neuronal activity in the dorsal raphe. In the present study, the effects of ethanol on the synthesis of 5‐HT and the expression of tryptophan hydroxylase (TPH), the rate‐limiting enzyme of 5‐HT synthesis, in the dorsal and median raphe of rats were investigated, using immunohistochemial methods. Results showed that the density of 5‐HT‐positive and TPH‐positive cells was reduced by ethanol treatment in a time‐dependent manner. Based on these results, it is suggested that the pathogenesis of ethanol‐induced neuropsychological disorders involves ethanol‐induced suppression of 5‐HT synthesis and TPH expression in the raphe region.