bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of polyamine catabolism by activated Ki‐ras in human colon cancer cells
Authors: Ignatenko Natalia A. , Babbar Naveen , Mehta Dipti , Casero Robert A. , Gerner Eugene W. 
Published: January 2004

AbstractAn activated Ki‐ras was expressed in the human colon adenocarcinoma cell line Caco‐2 to study the effects of Ki‐ras oncogene on polyamine metabolism during gastrointestinal tumorigenesis. Multiple clones selected for expression of the mutant Ki‐ras transgene displayed a suppression of transcription of a key catabolic enzyme in polyamine catabolism spermidine/spermine N1‐acetyltransferase (SSAT). Gene expression analysis, with cDNA microarrays, showed that Ki‐ras transfected clones had decreased levels of expression, compared to mock transfected cells, of peroxisome proliferator‐activated receptor gamma (PPARγ), a member of the nuclear hormone receptor family and an important regulator of cell proliferation and differentiation. The activated Ki‐ras suppressed SSAT expression by a mechanism involving the PPARγ response element (PPRE) located at +48 bp relative to the transcription start site of the SSAT gene. Transient expression of the PPARγ protein in Ki‐ras expressing Caco‐2 clones, or treatment with the PPARγ ligand ciglitazone, led to an increase in the SSAT promoter activity. A MEK1/2 inhibitor PD98059 induced transcription of both PPARγ and SSAT genes in the activated Ki‐ras clones, suggesting that the mitogen‐activated protein kinases (MAPKs) were involved in the regulation of SSAT expression by PPARγ. We concluded that mutated Ki‐ras suppressed SSAT via a transcriptional mechanism involving the PPARγ signaling pathway. © 2004 Wiley‐Liss, Inc.
Molecular mechanisms for apigenin‐induced cell‐cycle arrest and apoptosis of hormone refractory human prostate carcinoma DU145 cells
Authors: Shukla Sanjeev , Gupta Sanjay 
Published: January 2004

AbstractDevelopment of effective agents for treatment of hormone‐refractory prostate cancer has become a national medical priority. We have reported recently that apigenin (4′,5,7‐trihydroxyflavone), found in many common fruits and vegetables, has shown remarkable effects in inhibiting cell growth and inducing apoptosis in many human prostate carcinoma cells. Here we demonstrate the molecular mechanism of inhibitory action of apigenin on androgen‐refractory human prostate carcinoma DU145 cells that have mutations in the tumor suppressor gene p53 and pRb. Treatment of cells with apigenin resulted in a dose‐ and time‐dependent inhibition of growth, colony formation, and G1 phase arrest of the cell cycle. This effect was associated with a marked decrease in the protein expression of cyclin D1, D2, and E and their activating partner, cyclin‐dependent kinase (cdk)2, 4, and 6, with concomitant upregulation of WAF1/p21, KIP1/p27, INK4a/p16, and INK4c/p18. The induction of WAF1/p21 and its growth inhibitory effects by apigenin appears to be independent of p53 and pRb status of these cells. Apigenin treatment also resulted in alteration in Bax/Bcl2 ratio in favor of apoptosis, which was associated with the release of cytochrome c and induction of apoptotic protease‐activating factor‐1 (Apaf‐1). This effect was found to result in a significant increase in cleaved fragments of caspase‐9, ‐3, and poly(ADP‐ribose) polymerase (PARP). Further, apigenin treatment resulted in downmodulation of the constitutive expression of nuclear factor‐kappaB (NF‐κB)/p65 and NF‐κB/p50 in the nuclear fraction that correlated with an increase in the expression of IkappaB‐alpha (IκBα) in the cytosol. Taken together, we concluded that molecular mechanisms during apigenin‐mediated growth inhibition and induction of apoptosis in DU145 cells was due to (1) modulation in cell‐cycle machinery, (2) disruption of mitochondrial function, and (3) NF‐κB inhibition. © 2004 Wiley‐Liss, Inc.
Kinetics of myc‐max‐mad gene expression during hepatocyte proliferation in vivo: Differential regulation of mad family and stress‐mediated induction of c‐myc
Authors: Mauleon Itsaso , Lombard Marie‐Noëlle , Muñoz‐Alonso Maria J. , Cañelles Matilde , Leon Javier 
Published: January 2004

AbstractMad proteins (Mad1, Mxi1, Mad3, Mad4, Mnt/Rox) are biochemical and biological antagonists of c‐Myc oncoprotein. Mad‐Max dimers repress the transcription of the same target genes activated by Myc‐Max dimers. Despite the critical role of Max and Mad proteins as modulators of c‐Myc functions, there are no comparative data on their regulation in vivo. We carried out a systematic analysis of c‐myc, max, and mad family expression in a model of synchronized cell proliferation in vivo in adult tissues, that is, rat hepatocytes after partial hepatectomy. We confirmed the previously reported early peak of c‐myc expression after hepatectomy but we show that it did not correlate with hepatocyte proliferation as it also occurred in sham‐operated animals as a result of surgical stresses. A second peak of c‐myc expression was observed later, at the time of the wave of DNA synthesis. No such expression was detected in sham‐operated rat quiescent hepatocytes. max expression increased around 4–16 h after hepatectomy, before the peaks of c‐myc and DNA synthesis. mxi1 and mad4 were slightly downregulated during liver regeneration. mnt/rox expression did not change. These expression patterns suggest a role of Myc‐Max for efficient mitogenic response of hepatocytes. We also analyzed the effects of Myc and Max ectopic expression on the clonogenic growth of the rat hepatoma cells. Expression of c‐Myc and Max increased clonogenic growth, whereas the reduction of c‐Myc levels by an antisense vector decreased growth. The results suggest nonredundant roles for mad genes in hepatocyte proliferation and point to c‐Myc as a putative target for anticancer therapy of liver cancer. © 2004 Wiley‐Liss, Inc.
Imbalance of antioxidant enzymes in tumor cells and inhibition of proliferation and malignant features by scavenging hydrogen peroxide
Authors: Policastro Lucía , Molinari Beatriz , Larcher Fernando , Blanco Patricia , Podhajcer Osvaldo L. , Costa Cristina S. , Rojas Paola , Durán Hebe 
Published: January 2004

AbstractThe aim of this study was to evaluate the endogenous alterations of the antioxidant enzymes in tumor cells and to specifically compensate the resulting changes in the levels of reactive oxygen species (ROS) to control the malignant growth. We determined and compared the activities of antioxidant enzymes and the levels of superoxide anion (${\rm O}_{\rm 2}^{ \cdot - }$) and hydrogen peroxide (H2O2) in tumor cell lines with different degrees of malignancy, paired with regard to their origin (PB/CH72T4, PDV/PDVC57, and HBL‐100/MCF‐7). An increase in superoxide dismutase activity and a decrease in the activities of H2O2‐detoxifying enzymes, as a function of malignancy, coupled with a rise in H2O2 and a decrease in ${\rm O}_{\rm 2}^{ \cdot - }$ were demonstrated. Treatment of cells with exogenous catalase showed a dose‐dependent inhibition of proliferation. This inhibition was also demonstrated in several cell lines of different tissue origin and species, suggesting a general role of H2O2 in cell proliferation. Moreover, stable expression of human catalase in MCF‐7 cells inhibited proliferation and also reverted malignant features. We conclude that H2O2 played a crucial and general role in the regulation of proliferation and that an endogenous imbalance in antioxidant enzymes could be a relevant event in the carcinogenesis process. © 2004 Wiley‐Liss, Inc.
Modulation of DNA hypomethylation as a surrogate endpoint biomarker for chemoprevention of colon cancer
Authors: Tao Lianhui , Wang Wei , Kramer Paula M. , Lubet Ronald A. , Steele Vernon E. , Pereira Michael A. 
Published: January 2004

AbstractSurrogate end‐point biomarkers are being developed as indicators of the efficacy of chemopreventive agents. These biomarkers are molecular and biological end‐points that can be modulated by chemopreventive agents in accordance with their efficacy to prevent cancer. DNA hypomethylation is a common alteration found in colon tumors that has the potential of being modulated by chemopreventive agents and thus being useful as a surrogate end‐point biomarker. Agents that were either effective or ineffective in preventing colon cancer were evaluated for the ability to modulate DNA hypomethylation in azoxymethane‐induced colon tumors in male F344 rats. DNA methylation was determined by Dot Blot Analysis using a mouse monoclonal anti‐5‐methylcytosine antibody. Colon tumors had a 70% reduction in DNA methylation relative to normal colonic mucosa. DNA methylation in the tumors was increased by 7 days of treatment with agents that have been shown to prevent colon cancer (calcium chloride, α‐diflouromethylornithine [DFMO], piroxicam, and sulindac), whereas agents shown not to prevent colon cancer in rats (low dose aspirin, 2‐carboxyphenyl retinamide [2‐CPR], quercetin, 9‐cis retinoic acid, and rutin) did not increase DNA methylation. The results suggest that the ability to reverse the DNA hypomethylation in colon tumors could be useful as a surrogate end‐point biomarker for chemoprevention of colon cancer. © 2004 Wiley‐Liss, Inc.
Modelling of an underground waste disposal site by upscaling
Authors: Bourgeat A. , Gipouloux O. , Marušić‐Paloka E. 
Published: January 2004

AbstractIn this paper, we study the global behaviour of an underground waste disposal in order to have an accurate upscaled model suitable for the computations involved in safety assessment processes. We start from a detailed model describing the transport of pollutant leaking from a high number of units. Using the method of homogenization, going to the limit, we obtain first a macroscopic model where the sources are now appearing globally. Then we compute a first‐order matched asymptotic expansion and we give the error estimates for this approximation. Copyright © 2004 John Wiley & Sons, Ltd.
Does fractional anisotropy have better noise immunity characteristics than relative anisotropy in diffusion tensor MRI? An analytical approach
Authors: Hasan Khader M. , Alexander Andrew L. , Narayana Ponnada A. 
Published: January 2004

AbstractFractional anisotropy (FA) and relative anisotropy (RA) are the two most commonly used scalar measures of anisotropy in diffusion tensor (DT) MRI. While a few published studies have shown that FA has superior noise immunity relative to RA, no theoretical basis has been proposed to explain this behavior. In the current study, the diffusion tensor invariants were used to derive a simple analytical expression that directly relates RA and FA. An analysis based on that analytical expression demonstrated that the FA images have a higher signal‐to‐noise ratio (SNR) than RA for any value of tensor anisotropy RA or FA > 0. This theoretical behavior was verified using both Monte Carlo simulations and bootstrap analysis of DT‐MRI data acquired in a spherical water phantom and normal human subjects. Magn Reson Med 51:413–417, 2004. © 2004 Wiley‐Liss, Inc.
Noninvasive monitoring of stem cell transfer for muscle disorders
Authors: Walter Glenn A. , Cahill Kevin S. , Huard Johnny , Feng Huisheng , Douglas T. , Sweeney H. Lee , Bulte Jeff W.M. 
Published: January 2004

AbstractIn this study the ability of magnetodendrimers to efficiently label cultured muscle stem cells and allow for subsequent in vivo cell detection was determined. Magnetodendrimer‐labeled cells exhibited normal growth rates in culture, and retained their capacity to undergo proliferation and form normal myotubes. Labeled stem cells possessed high in vivo proton relaxivities that enhanced MRI contrast properties and enabled us to noninvasively monitor the stem cells' incorporation into dystrophic muscle. Well defined regions of decreased signal intensity were observed in both T2‐ and T1‐weighted image sequences. MRI was used to longitudinally follow stem cell dynamics in dystrophic muscle with in‐plane resolutions on the order of a single muscle fiber (22 × 43 μm2). Regions of decreased signal intensity were well correlated with iron accumulation and other histochemical markers of stem cell incorporation. We concluded that this technique may be useful for continuous noninvasive readouts of stem cell transfer, replacing sequential muscle biopsies and tissue harvesting. Magn Reson Med 51:273–277, 2004. © 2004 Wiley‐Liss, Inc.
Iterative Next‐Neighbor Regridding (INNG): Improved reconstruction from nonuniformly sampled k‐space data using rescaled matrices
Authors: Moriguchi Hisamoto , Duerk Jeffrey L. 
Published: January 2004

AbstractThe reconstruction of MR images from nonrectilinearly sampled data is complicated by the fact that the inverse 2D Fourier transform (FT) cannot be performed directly on the acquired k‐space data set. k‐Space gridding is commonly used because it is an efficient reconstruction method. However, conventional gridding requires optimized density compensation functions (DCFs) to avoid profile distortions. Oftentimes, the calculation of optimized DCFs presents an additional challenge in obtaining an accurately gridded reconstruction. Another type of gridding algorithm, the block uniform resampling (BURS) algorithm, often requires singular value decomposition (SVD) regularization to avoid amplification of data imperfections, and under some conditions it is difficult to adjust the regularization parameters. In this work, new reconstruction algorithms for nonuniformly sampled k‐space data are presented. In the newly proposed algorithms, high‐quality reconstructed images are obtained from an iterative reconstruction that is performed using matrices scaled to sizes greater than that of the target image matrix. A second version partitions the sampled k‐space region into several blocks to avoid limitations that could result from performing multiple 2D‐FFTs on large data matrices. The newly proposed algorithms are a simple alternative approach to previously proposed optimized gridding algorithms. Magn Reson Med 51:343–352, 2004. © 2004 Wiley‐Liss, Inc.
Influence of body temperature on the BOLD effect in murine SCC tumors†
Authors: Reijnders Koen , English Sean J. , Krishna Murali C. , Cook John A. , Sowers Anastasia L. , Mitchell James B. , Zhang Yantian 
Published: January 2004

AbstractChanges in the blood oxygen level dependent (BOLD) enhancements in tumors (squamous cell carcinoma, (SCCVII)) implanted in mice maintained at core temperatures of 30°C or 37°C were measured using MRI and compared to tumor oxygen levels obtained using an oxygen‐sensitive Eppendorf electrode. Tumors were implanted in a hindleg of the mice intramuscularly. Tumor‐bearing mice were imaged by BOLD MRI, while first breathing air and then carbogen (95% O2, 5% CO2) for 15‐min intervals at a core temperature of 30°C. After an equilibration period, the identical regimen was conducted with the same animal maintained at 37°C. This procedure was repeated with additional mice starting at 37°C followed by imaging at 30°C. Likewise, oxygen electrode measurements of the tumor were determined at core temperatures of 30°C and 37°C. The Eppendorf measurements showed that tumors in animals maintained at 30°C were significantly more hypoxic than at 37°C. MRI studies demonstrated stronger BOLD enhancement at 30°C than at 37°C, suggesting significant changes in hypoxia and/or blood flow in tumors at these temperatures. The findings of the study stress the importance of maintaining normal core temperature when assessing tumor oxygen status using functional imaging modalities or oxygen‐sensitive electrodes. Magn Reson Med 51:389–393, 2004. Published 2004 Wiley‐Liss, Inc.
Steady‐state diffusion‐weighted imaging of in vivo knee cartilage
Authors: Miller Karla L. , Hargreaves Brian A. , Gold Garry E. , Pauly John M. 
Published: January 2004

AbstractDiffusion‐weighted imaging (DWI) has strong potential as a diagnostic for early cartilage damage, with clinical impact for diseases such as osteoarthritis. However, in vivo DWI of cartilage has proven difficult with conventional methods due to the short T2. This work presents a 3D steady‐state DWI sequence that is able to image short‐T2 species with high SNR. When combined with 2D navigator correction of motion‐induced phase artifacts, this method enables high resolution in vivo DWI of cartilage. In vivo knee images in healthy subjects are presented with high SNR (SNR = 110) and submillimeter in‐plane resolution (0.5 × 0.7 × 3.0 mm3). A method for fitting the diffusion coefficient is presented which produces fits within 10% of literature values. This method should be applicable to other short‐T2 tissues, such as muscle, which are difficult to image using traditional DWI methods. Magn Reson Med 51:394–398, 2004. © 2004 Wiley‐Liss, Inc.
Active deep brain stimulation during MRI: A feasibility study
Authors: Georgi J.‐C. , Stippich C. , Tronnier V.M. , Heiland S. 
Published: January 2004

AbstractThe goal of this study was to evaluate the feasibility of active deep brain stimulation (DBS) during the application of standard clinical sequences for functional MRI (fMRI) in phantom measurements. During active DBS, we investigated induced voltage, temperature at the electrode tips and lead, forces on the electrode and lead, consequences of defective leads and loose connections, proper operation of the neurostimulator, and image quality. Sequences for diffusion‐ and perfusion‐weighted imaging, fMRI, and morphologic MRI were used. The DBS electrode and lead were placed in a NaCl solution‐filled phantom. The results indicate that there are severe potential hazards for patients. Strong heating, high induced voltage, and even sparking at defects in the connecting cable could be observed. However, it was demonstrated that under certain conditions, safe MR examinations during active DBS are feasible. Certain safety precautions are recommended in this report. Magn Reson Med 51:380–388, 2004. © 2004 Wiley‐Liss, Inc.
Enhancing measured diffusion anisotropy in gray matter by eliminating CSF contamination with FLAIR
Authors: Ma Xiangyang , Kadah Yasser M. , LaConte Stephen M. , Hu Xiaoping 
Published: January 2004

AbstractIn this work, the effect of fluid‐attenuated inversion recovery (FLAIR) on measured diffusion anisotropy was investigated in gray matter. DTI data were obtained with and without FLAIR in six normal volunteers. The application of FLAIR was experimentally demonstrated to lead to a consistent increase in fractional anisotropy (FA) in gray‐matter regions, which was attributed to suppressed partial volume effects from CSF. In addition to these experimental results, Monte Carlo simulations were performed to ascertain the effect of noise on the measured FA under the experimental conditions of this study. The experimentally observed effect of noise was corroborated by the simulation, indicating that the increase in the measured FA was not due to a noise‐related bias but to an actual increase in diffusion anisotropy. This enhanced measurement of diffusion anisotropy can be potentially used to differentiate directionally dependent structure and tracking fibers in gray matter. Magn Reson Med 51:423–427, 2004. © 2004 Wiley‐Liss, Inc.
Electrodiagnostic studies in the management and prognosis of neuromuscular disorders
Authors: Gilchrist James M. , Sachs George M. 
Published: January 2004

AbstractPrognosis remains a neglected aspect of modern medical care and research, behind diagnosis and treatment. The very term “electrodiagnosis” implies as much. Despite this, much has been published regarding the use and benefit of electrodiagnostic techniques in assessing prognosis and assisting in management of patients after the diagnosis has been established. This information is often hidden or otherwise not emphasized. This review summarizes the literature regarding the use of such techniques for prognosis and management of disorders of lower motor neurons, peripheral nerves, neuromuscular transmission, and muscle. Muscle Nerve 29: 165–190, 2004
Adult polyglucosan body disease: Case description of an expanding genetic and clinical syndrome
Authors: Klein Christopher J. , Boes Christopher J. , Chapin John E. , Lynch Christopher D. , Campeau Norbert G. , Dyck P. James B. , Dyck Peter J. 
Published: January 2004

AbstractA non‐Jewish patient is described who had adult polyglucosan body disease (APBD) and glycogen branching enzyme (GBE) deficiency without GBE mutation. A heterozygous polymorphism (Val160Ile) was found, and also discovered in 1 of 50 normal individuals. Magnetic resonance imaging demonstrated increased T2 signal in the midbrain, medullary olives, dentate nuclei, cerebellar peduncles, and internal and external capsules, with vermian atrophy. Both muscle and nerve biopsy revealed perivascular inflammatory infiltrates. These findings expand the clinical and genetic spectrum of APBD. Factors other than mutation of the expressed GBE gene may cause enzyme deficiency and varied expression and development of APBD. Muscle Nerve 29: 323‐328, 2004
Loss‐of‐function phenotype of hereditary neuropathy with liability to pressure palsies
Authors: Li Jun , Krajewski Karen , Lewis Richard A. , Shy Michael E. 
Published: January 2004

AbstractHereditary neuropathy with liability to pressure palsies (HNPP) provides a human model to investigate the role of PMP22 in myelinated peripheral nerve, since the disease is caused by a deletion of one of the two PMP22 alleles. To systematically characterize the phenotype of HNPP, we prospectively evaluated the clinical features and electrophysiological findings in 17 genetically confirmed patients, 7 men and 10 women, ranging in age from 9 to 66 years (mean, 41 ± 13). Fifteen symptomatic patients presented with episodes of transient focal weakness or sensory loss that were usually related to particular activities causing nerve compression, including stretching or minor repetitive focal trauma. No patient sought medical attention for symptoms of a symmetric polyneuropathy. Neurological examinations were either normal or mildly abnormal. Neither focal slowing of nerve conduction studies, nor reduction in compound muscle action potential (CMAP) or sensory nerve action potential (SNAP) amplitudes consistently predicted the site of symptoms. We conclude that the majority of patients with HNPP present with transient, recurrent, focal symptoms of weakness or sensory loss in the distribution of individual nerves or plexus, and that a diffuse symmetric sensorimotor polyneuropathy is an unusual presentation of HNPP. These studies suggest that the function of PMP22, at least in part, is to stabilize myelin so that it will be protected from injuries resulting from repetitive, minor trauma. Muscle Nerve 29: 205–210, 2004