bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of transgene expression on drug metabolism following systemic adenoviral vector administration
Authors: Callahan Shellie M. , Boquet Michael P. , Ming Xin , Brunner Lane J. , Croyle Maria A. 
Published: February 2006

AbstractBackgroundSystemic administration of a first‐generation adenovirus expressing E. coli beta‐galactosidase (AdlacZ) alters expression and function of two hepatic drug‐metabolizing enzymes, cytochrome P450 (CYP) 3A2 and 2C11, for 14 days. The objective of these studies was to determine how the transgene cassette influences CYP expression and function.MethodsSprague‐Dawley rats were given 5.7 × 1012 viral particles (vp)/kg of either: AdlacZ, Ad expressing murine erythropoietin (Epo), Ad without a transgene (Null), or phosphate‐buffered saline (Vehicle). Hepatic CYP protein expression, activity, mRNA and alanine aminotransferase (ALT) levels were analyzed 0.25, 1, 4, and 14 days following a single intravenous injection.ResultsAdministration of Epo did not alter CYP3A2 activity, but induced RNA levels by a factor of 2 at 4 and 14 days (P⩽0.01). This vector suppressed CYP2C11 activity levels by 45% at 1 day (P⩽0.05) and RNA levels throughout the study period (P⩽0.05). The Null vector suppressed CYP3A2 activity by 36, 63, 34, and 45% at 0.25, 1, 4 and 14 days, respectively (P⩽0.05). CYP2C11 activity was suppressed 1 day after administration (41%) and RNA levels were suppressed at 6 h (53%) and 1 day (36%, P⩽0.05). In contrast, AdlacZ suppressed both CYP3A2 and 2C11 at all time points.ConclusionsThe immunogenic and biological nature of the transgene cassette can influence changes in CYP3A2, but not the 2C11 isoform. The shift in transcription and translation of protein for maintenance of physiologic homeostasis to production of viral proteins and transgene product and their associated toxicity during viral infection may explain our observations. Copyright © 2006 John Wiley & Sons, Ltd.
α‐Melanocyte‐stimulating hormone gene therapy reverses carbon tetrachloride induced liver fibrosis in mice
Authors: Lee Tsung‐Hsing , Jawan Bruno , Chou Wen‐Ying , Lu Cheng‐Nan , Wu Chia‐Ling , Kuo Hsiao‐Mei , Concejero Allan M. , Wang Cheng‐Haung 
Published: February 2006

AbstractBackgroundHepatic fibrosis represents a process of healing and scarring in response to chronic liver injury. Effective therapies are lacking. We have previously demonstrated that α‐melanocyte‐stimulating hormone (α‐MSH) gene therapy protects against thioacetamide‐induced acute liver failure in mice. Recent reports showed that collagen metabolism is a novel target of α‐MSH. Therefore, the aim of this study is to investigate whether α‐MSH gene therapy possesses anti‐hepatic fibrogenic effect in mice.MethodsLiver fibrosis was induced in mice by administering carbon tetrachloride (CCl4) continuously for 10 weeks. α‐MSH expression plasmid was delivered via electroporation after liver fibrosis had been established. Histopathology, reverse‐transcription polymerase chain reaction (RT‐PCR), immunoblotting, and gelatin zymography were used to investigate its possible mechanisms of action.Resultsα‐MSH gene therapy reversed established liver fibrosis in CCl4‐treated mice. RT‐PCR revealed that α‐MSH gene therapy attenuated the liver TGF‐β1, collagen α1, and cell adhesion molecule mRNA upregulation. Following gene transfer, both the activation of α‐smooth muscle actin (α‐SMA) and cyclooxygenase‐2 (COX‐2) was significantly attenuated. Further, α‐MSH significantly increased matrix metalloproteinase (MMP) activity with tissue inhibitors of matrix metalloproteinase (TIMP) inactivation.ConclusionsWe have demonstrated that α‐MSH gene therapy reversed established liver fibrosis in mice. It also prevented the upregulated fibrogenic and proinflammatory gene response after CCl4administration. Its collagenolytic effect may be attributed to MMP and TIMP modulation. In summary, α‐MSH gene therapy may be an effective therapeutic modality against liver fibrosis with potential clinical use. Copyright © 2006 John Wiley & Sons, Ltd.
Synthesis of fluorine‐18‐labelled 5‐ and 6‐fluoro‐2‐pyridinamine
Authors: Abrahim Aiman , Angelberger Peter , Kletter Kurt , Müller Markus , Joukhadar Christian , Erker Thomas , Langer Oliver 
Published: March 2006

AbstractA one‐pot radiosynthesis method to prepare the new fluorine‐18‐labelled fluoropyridine derivatives 5‐[18F]fluoro‐2‐pyridinamine and 6‐[18F]fluoro‐2‐pyridinamine in two to three reaction steps was developed. The first step consisted of no‐carrier‐added nucleophilic aromatic substitution of commercially available halogen‐substituted 2‐pyridinecarboxamide or 2‐pyridinecarbonitrile derivatives with K[18F]F‐K222 in DMSO at 150–180°C. The [18F]fluoride incorporation yields ranged from 67 to 98% for all studied precursor molecules. It is remarkable that 5‐bromo‐2‐pyridinecarbonitrile gave almost quantitative [18F]fluoride incorporation at the meta‐position (5‐position) of the pyridine ring after only 5 min of heating at 150°C. After base‐catalysed hydrolysis of the [18F]fluorinated pyridinecarbonitriles into their corresponding carboxamides, the latter were transformed in a Hofmann‐type rearrangement reaction into the respective amines by treatment of crude reaction mixtures with bromine and aqueous base (20–30% conversion yield). Reaction mixtures were purified by reversed‐phase semipreparative HPLC followed by strong cation exchange solid‐phase extraction to afford 5‐[18F]fluoro‐2‐pyridinamine and 6‐[18F]fluoro‐2‐pyridinamine in non‐decay‐corrected radiochemical yields of 6–10% in a total synthesis time of 83–112 min. The preparation of 5‐[18F]fluoro‐2‐pyridinamine is one of very few examples demonstrating the feasibility of nucleophilic meta‐[18F]fluorination of a pyridine derivative. Both 5‐[18F]fluoro‐2‐pyridinamine and 6‐[18F]fluoro‐2‐pyridinamine are new potentially useful radiolabelled synthons for radiopharmaceutical chemistry. Copyright © 2006 John Wiley & Sons, Ltd.
Local staging of rectal cancer using combined pelvic phased‐array and endorectal coil MRI
Authors: Tatli Servet , Mortele Koenraad J. , Breen Elizabeth L. , Bleday Ronald , Silverman Stuart G. 
Published: March 2006

AbstractPurposeTo assess the accuracy of MRI, using a pelvic phased‐array coil and an endorectal coil, for preoperative local staging of rectal cancer.Materials and MethodsFifty‐one patients (26 males and 25 females) with adenocarcinoma of the rectum underwent preoperative MRI and surgical resection of their tumors. Surgical pathology staging was compared to MRI staging (using the TNM classification) obtained both retrospectively by a reader blinded to surgical findings and prospectively (radiological reports). In addition, patients were stratified according to surgical treatment groups (stage I = T1‐2/N0, stage II = T3/N0, stage III = Tx/N1‐2).ResultsAt pathology, 36 of 51 (68%) tumors were classified as T0‐T2, and 15 (32%) were classified as T3. Overall, the sensitivity and specificity of MRI readings for T3 staging were 93% and 86%, respectively (positive predictive value (PPV) = 74%, negative predictive value (NPV) = 97%, accuracy = 88%). MRI correctly predicted lymph node metastases in 11 of 13 patients with a sensitivity of 85% and specificity of 69% (PPV = 58%, NPV = 90%, accuracy = 74%). MRI correctly predicted surgical treatment groups in 33 of 39 (85%) patients. Interobserver agreement between the retrospective and prospective readings was excellent (κ = 0.85) for prediction of T3 tumor and good (κ = 0.80) for prediction of nodal involvement.ConclusionCombined endorectal and pelvic phased‐array coil MRI can be used reliably to select which patients should receive preoperative chemoradiotherapy. It is highly predictive in terms of excluding T3 tumors, but still has limitations in predicting lymph node metastasis. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
T1ρ relaxation mapping in human osteoarthritis (OA) cartilage: Comparison of T1ρ with T2
Authors: Regatte Ravinder R. , Akella Sarma V.S. , Lonner J.H. , Kneeland J.B. , Reddy Ravinder 
Published: March 2006

AbstractPurposeTo quantify the spin‐lattice relaxation time in the rotating frame (T1ρ) in various clinical grades of human osteoarthritis (OA) cartilage specimens obtained from total knee replacement surgery, and to correlate the T1ρ with OA disease progression and compare it with the transverse relaxation time (T2).Materials and MethodsHuman cartilage specimens were obtained from consenting patients (N = 8) who underwent total replacement of the knee joint at the Pennsylvania Hospital, Philadelphia, PA, USA. T2‐ and T1ρ‐weighted images were obtained on a 4.0 Tesla whole‐body GE Signa scanner (GEMS, Milwaukee, WI, USA). A 7‐cm diameter transmit/receive quadrature birdcage coil tuned to 170 MHz was employed.ResultsAll of the surgical knee replacement OA cartilage specimens showed elevated relaxation times (T2 and T1ρ) compared to healthy cartilage tissue. In various grades of OA specimens, the T1ρ relaxation times varied from 62 ± 5 msec to 100 ± 8 msec (mean ± SEM) depending on the degree of cartilage degeneration. However, T2 relaxation times varied only from 32 ± 2 msec to 45 ± 4 msec (mean ± SEM) on the same cartilage specimens. The increase in T2 and T1ρ in various clinical grades of OA specimens were ∼5–50% and 30–120%, respectively, compared to healthy specimens. The degenerative status of the cartilage specimens was also confirmed by histological evaluation.ConclusionPreliminary results from a limited number of knee specimens (N = 8) suggest that T1ρ relaxation mapping is a sensitive noninvasive marker for quantitatively predicting and monitoring the status of macromolecules in early OA. Furthermore, T1ρ has a higher dynamic range (>100%) for detecting early pathology compared to T2. This higher dynamic range can be exploited to measure even small macromolecular changes with greater accuracy compared to T2. Because of these advantages, T1ρ relaxation mapping may be useful for evaluating early OA therapy. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Interactive magnetic resonance cholangiography (MRC) with adaptive averaging
Authors: Graves Martin J. , Kershaw Lucy E. , Black Richard T. , Sala Evis , Skinner Jane , Lomas David J. 
Published: March 2006

AbstractPurposeTo implement and evaluate a technique for adaptively averaging 2D magnetic resonance cholangiography (MRC) images obtained using an interactive imaging system with a view to improving image quality at reduced fields of view (FOVs).Materials and MethodsImages were obtained using an interactive implementation of a single‐shot half‐Fourier rapid acquisition with relaxation enhancement (RARE) technique. Software was developed for adaptively averaging images, and an evaluation was performed in a phantom and a cohort of 10 patients referred for standard MRC. Adaptively averaged and standard single‐shot MRC images were evaluated with respect to their ability to demonstrate the common bile duct and main left and right intrahepatic duct branches.ResultsIn all patient studies there was no difference in the ability of either the adaptive technique or the standard single‐shot method to demonstrate the common bile duct and the main left and right intrahepatic duct branches. However, in seven of the 10 patient studies the adaptive technique provided better visualization of the peripheral bile duct system (P = 0.035; sign test). There was no difference in the diagnostic confidence of the two techniques (P = 0.32, Wilcoxon signed‐rank test).ConclusionAdaptive averaging of MRC images obtained using an interactive imaging paradigm significantly improves visualization of peripheral intrahepatic ducts. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Hemodynamic characterization of focal hepatic lesions: Role of ferucarbotran‐enhanced dynamic MR imaging using T2‐weighted multishot spin‐echo echo‐planar sequence
Authors: Hori Masatoshi , Murakami Takamichi , Kim Tonsok , Iannaccone Riccardo , Abe Hisashi , Onishi Hiromitsu , Tomoda Kaname , Catalano Carlo , Passariello Roberto , Nakamura Hironobu 
Published: March 2006

AbstractPurposeTo investigate the role of ferucarbotran‐enhanced dynamic MR imaging using multishot spin‐echo echo‐planar sequence in the evaluation of hemodynamics of focal hepatic lesions.Materials and MethodsSixty‐three focal hepatic lesions (24 benign and 39 malignant) from 53 consecutive patients who underwent both ferucarbotran‐enhanced MR imaging and dynamic computed tomography (CT) were included in this study. MR imaging was performed with a 1.5‐T scanner with a phased‐array coil. T2‐weighted multishot spin‐echo echo‐planar sequences (TR/TE = 1714–2813/80 msec) were obtained during a single breathhold before and 15, 60, 120, 180, and 600 seconds after intravenous injection of ferucarbotran. The enhancement patterns of lesions were classified into three categories by a study coordinator on the basis of dynamic CT images as hypervascular, hypovascular, and hemangioma type. The study coordinator created mean contrast‐to‐noise ratio of lesions vs. time curves for each enhancement pattern for quantitative analyses. Moreover, three radiologists separately and blindly reviewed MR images, and then assigned three confidence scores for the three enhancement patterns to each lesion. Sensitivity, specificity, and receiver operating characteristic analyses were performed.ResultsQuantitative analyses showed characteristic enhancement curves for each enhancement pattern. Mean sensitivities/specificities were 0.816/0.882, 0.897/0.863, and 0.800/0.989 for hypervascular, hypovascular, and hemangioma types, respectively. Mean areas under the receiver operating characteristic curve were 0.886 for hypervascular type and 0.913 for hypovascular type.ConclusionFerucarbotran‐enhanced dynamic MR imaging can be used to successfully characterize the hemodynamics of focal hepatic lesions. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Magnetic resonance imaging of tissue and vascular layers in the cat retina
Authors: Shen Qiang , Cheng Haiying , Pardue Machelle T. , Chang Thomas F. , Nair Govind , Vo Van Toi , Shonat Ross D. , Duong Timothy Q. 
Published: March 2006

AbstractPurposeTo report the visual resolution of multiple cell and vascular “layers” in the cat retina using MRI.Materials and MethodsT2‐ and diffusion‐weighted MRI at 4.7 Tesla was performed. Layer‐specific thickness, T2, spin density, apparent diffusion coefficient perpendicular (ADC⟂) and parallel (ADC∥) to the retinal surface were tabulated. T1‐weighted MRI was acquired before and after intravenous administration of Gd‐DTPA and subtraction images were obtained. Histology was performed for validation.ResultsThree distinct “layers” were observed. The inner strip nearest to the vitreous (exhibiting large T2, ADC, spin density with Gd‐DTPA enhancement) overlapped the ganglion cell layer, bipolar cell layer, and the embedded retinal vascular layer. The middle strip (exhibiting small T2, ADC, spin density without Gd‐DTPA enhancement) overlapped the photoreceptor cell layer and the inner and outer segments. The outer strip (exhibiting large T2, ADC, spin density with Gd‐DTPA enhancement) overlapped the tapetum and choroidal vascular layer. T2, spin density, ADC⟂ and ADC∥ of different “layers” were tabulated. The inner strip was slightly thicker than the other two strips. The total thickness, including neural and nonneural retina, was 358 ± 13μm (N = 6) by MRI and 319 ± 77 μm (N = 5) by histology.ConclusionMRI provides a noninvasive tool to study the retina with laminar specificity without depth limitation. J. Magn. Reson. Imaging 2006. Published 2006 Wiley‐Liss, Inc.
Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice
Authors: Denny Christine A. , Kasperzyk Julie L. , Gorham Kristen N. , Bronson Roderick T. , Seyfried Thomas N. 
Published: March 2006

AbstractCaloric restriction (CR), which improves health and increases longevity, was studied as a therapy in a hexosaminidase β knockout mouse model of Sandhoff disease (SD), an incurable neurodegenerative disease involving accumulation of brain ganglioside GM2 and asialo‐GM2 (GA2). Adult mice were fed a rodent chow diet either ad libitum (AL) or restricted to reduce body weight by 15–18% (CR). Although GM2 and GA2 were elevated, no significant differences were seen between the Hexb−/− and the Hexb+/− mice for most brain phospholipids and cholesterol. Cerebrosides and sulfatides were reduced in the Hexb−/− mice. In addition, rotorod performance was significantly worse in the Hexb−/− mice than in the Hexb+/− mice. CR, which decreased circulating glucose and elevated ketone bodies, significantly improved rotorod performance and extended longevity in the Hexb−/− mice but had no significant effect on brain lipid composition or on cytoplasmic neuronal vacuoles. The expression of CD68 and F4/80 was significantly less in the CR‐fed than in the AL‐fed Hexb−/− mice. We suggest that the CR delays disease progression in SD and possibly in other ganglioside storage diseases through anti‐inflammatory mechanisms. © 2006 Wiley‐Liss, Inc.
Interferon‐γ is up‐regulated in the hippocampus in response to intermittent fasting and protects hippocampal neurons against excitotoxicity
Authors: Lee Jaewon , Kim So Jung , Son Tae Gen , Chan Sic L. , Mattson Mark P. 
Published: March 2006

AbstractDietary restriction (DR) increases the life span of many different organisms, and recent findings have demonstrated neuroprotective effects of DR in rodent and nonhuman primate models of neurodegenerative disorders. The neuroprotective mechanism of action of DR is unknown, but it may result from a mild cellular stress response involving increased production of neurotrophic factors. Because several different cytokines are known to be up‐regulated in brain cells in response to stress, we determined whether DR affected cytokine expression in the rat brain. Levels of expression of interferon‐γ (IFN‐γ) and its receptor were significantly increased in the hippocampus of rats that had been maintained on an intermittent fasting DR regimen compared with rats on the ad libitum control diet. Pretreatment of embryonic rat hippocampal cell cultures with IFN‐γ protected neurons against glutamate‐induced death. IFN‐γ‐mediated neuroprotection was associated with an enhanced recovery of intracellular Ca2+ concentrations following exposure to glutamate. Our data show that intermittent fasting DR stimulates IFN‐γ‐mediated neuroprotective signaling in the hippocampus, suggesting a role for this cytokine in the previously reported ability of DR to protect neurons in animal models of severe epileptic seizures, stroke, and neurodegenerative disorders. © 2006 Wiley‐Liss, Inc.
Rac/Rho pathway regulates actin depolymerization induced by aminoglycoside antibiotics
Authors: Jiang Hongyan , Sha Su‐Hua , Schacht Jochen 
Published: March 2006

AbstractStress stimuli can lead to remodeling of the actin cytoskeleton and subsequent alteration of cell adhesion and permeation as well as cell functions and cell fate. We investigated redox‐dependent Rho GTPase‐linked pathways controlling the actin cytoskeleton in the inner ear of the CBA mouse, by using aminoglycoside antibiotics as a noxious stimulus that causes loss of sensory cells via the formation of reactive oxygen species. Kanamycin treatment in vivo interfered with the formation of F‐actin, disturbed the arrangement of β‐actin in the stereocilia of outer hair cells, and altered the intermittent adherens junction/tight junction complexes between outer hair cells and supporting cells. The drug treatment also activated Rac1 and promoted the formation of the complex of Rac1 and p67phox while decreasing the activity of RhoA and reducing the formation of the RhoA/p140mDia complex. In inner‐ear‐derived cell lines, expression of mutated Rac1 changed the structural arrangement of F‐actin and diminished the immunoreactivity of p140mDia. These findings suggest that actin depolymerization induced by kanamycin is mediated by Rac1 activation, followed by the formation of superoxide by NADPH oxidase. These changes will ultimately contribute to aminoglycoside‐induced loss of hair cells. © 2006 Wiley‐Liss, Inc.
The Early Pleistocene Praetiglian and Ludhamian pollen stages in the North Sea Basin and their relationship to the marine isotope record
Authors: Meijer T. , Cleveringa P. , Munsterman D. K. , Verreussel R. M. C. H. 
Published: February 2006

AbstractIn this paper, the currently accepted correlation of the Early Pleistocene Ludhamian stage of England with the Tiglian‐A sub‐stage of the Netherlands is challenged. Recent investigations of Early Pleistocene marine North Sea deposits from a borehole near Noordwijk (the Netherlands) yielded evidence from molluscs, dinoflagellate cysts and sporomorphs for an alternation of warm‐temperate and arctic intervals within the Praetiglian and Tiglian stages. Marine equivalents of the terrestrial‐based pollen sub‐stages Tiglian A and B have been recognised in the upper part of the sequence. A Praetiglian age can be assigned to the lower part of the sequence on the basis of mollusc analysis. Within the Praetiglian, an alternation of warm and cold phases has been recognised from both the dinoflagellate cyst and molluscan records. Three cold phases within the Praetiglian are tentatively correlated with marine isotope stages (MIS) 96–100. The molluscan assemblages provide evidence for climate forcing of the sea level: highest sea levels are reached in the warm‐temperate intervals. Within the Praetiglian, an interval with an acme zone of the dinoflagellate cyst Impagidinium multiplexum, is correlated with the Ludhamian and tentatively linked to MIS 97 and/or MIS 96. The cold molluscan assemblages from the Noordwijk borehole include an acme zone of Megayoldia thraciaeformis, the first and only occurrence of this North Pacific bivalve in the North Sea Basin. Copyright © 2006 John Wiley & Sons, Ltd.
Late Quaternary upwelling off tropical NW Africa: new micropalaeontological evidence from ODP Hole 658C
Authors: Haslett Simon K. , Smart Christopher W. 
Published: February 2006

AbstractPlanktonic foraminifera and radiolaria have been analysed in a Late Quaternary (40–0 ka) sediment sequence from Ocean Drilling Program (ODP) Hole 658C located under a coastal upwelling system near Cap Blanc, offshore northwest Africa, in order to document the palaeoceanographic history of the area. Temporal variations in species abundance and faunal assemblage analysis reveal a tripartite phased sequence of palaeoceanographic change through the Late Quaternary. Phase 1 spans 40–14.5 ka and is characterised by moderate upwelling, but Heinrich event 2 is distinguished as a brief episode of strengthened upwelling. Phase 2 begins with a change in a number of variables at ca. 14.5 ka and extends to ca. 5.5 ka. This phase is characterised by a general strengthening of upwelling, but may be subdivided into three minor phases including (a) the recognition of the Younger Dryas, marked by a temporary reduction in upwelling strength, followed by (b) an intensification of upwelling, and (c) upwelling and high productivity between 8 and 5.5 ka. This phase of upwelling corresponds with maximum Holocene cooling, possibly triggered by the collapse of the Laurentide ice sheet. Phase 3 extends from 5.5 to 0 ka and is characterised by weak upwelling and significant calcite dissolution. These phases are related to climatic events, particularly the African Humid Period (AHP), which is coincident with Phase 2. The AHP is characterised by increased precipitation, linked to an intensification of the African monsoon that enhances North East Trade Wind‐driven coastal upwelling and is associated with the expansion of continental vegetation across North Africa. Copyright © 2006 John Wiley & Sons, Ltd.