bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutathione Depletion Renders Rat Hepatocytes Sensitive to Nitric Oxide Donor–Mediated Toxicity *
Authors: Chen Tracy , Pearce Linda L. , Peterson Jim , Stoyanovsky Detcho , Billiar Timothy R. 
Published: August 2005

Abstract

Nitric oxide (NO) can be either cytoprotective or cytotoxic in hepatocytes, depending on conditions within the cell. We hypothesized that redox status is a determinant of NO effects on cell viability. To cause the disturbance of redox homeostasis in the hepatocytes, cells were treated with the following glutathione (GSH) depleting agents: (1) chronic depletion by 18 hours pretreatment with buthionine sulfoximine (BSO), which depletes GSH by blocking its biosynthesis; and (2) acute depletion by 1 hour pretreatment with diethyl maleate (DEM), which conjugates GSH by the GSH-S-transferase catalyzed reaction.

s

-nitroso-
N

-acetyl-d,l-penicillamine (SNAP), a NO donor, was added after removal of GSH-depleting agents. Individual treatment with either SNAP or GSH depletion did not appreciably affect viability. A significant increase of cytotoxicity in hepatocytes was observed with the combination of a concentration and time course regimen of SNAP and GSH depletion. SNAP treatment of GSH-depleted hepatocytes led to an increase in LDH release and oxidative stress, disruption of mitochondrial membrane potential, the presence of nitrotyrosine (an indicator of peroxynitrite (ONOO−) generation), and a decrease in adenosine triphosphate (ATP) content. The interference of mitochondrial respiratory enzymes, especially with the combination treatments, indicated different levels of disturbance of electron transfer, superoxide generation, and ATP production. Other commonly used NO donors were found to exhibit lower and slower toxicity in the setting of GSH depletion than that evident with SNAP.
In conclusion
, the disruption of cellular redox homeostasis by GSH depletion leads hepatocytes to be more susceptible to NO (especially

S

-nitrosothiols) and subsequent necrotic cell death. (Hepatology 2005;42:598–607.)
Modeling the Current and Future Disease Burden of Hepatitis C Among Injection Drug Users in Scotland *
Authors: Hutchinson Sharon J. , Bird Sheila M. , Goldberg David J. 
Published: August 2005

Abstract

Quantitative estimates of the current and future burden of hepatitis C virus (HCV) disease are required to plan a public health response to the HCV epidemic with regard to both prevention and treatment. A forward projection model was used to estimate the numbers of both current and former injecting drug users (IDUs) who acquired HCV and progressed to moderate and severe disease in Glasgow and Scotland during 1960-2030. The model was designed to synthesize information on the incidence and cessation of injecting drug use, the incidence of HCV infection among IDUs, the rate of HCV disease progression, and the annual number of IDUs developing HCV-related decompensated cirrhosis. During 2003, a total of 17,400 and 42,900 HCV-infected IDUs were estimated in Glasgow and Scotland, respectively; this compares with approximately 5,000 and 13,900 diagnosed, respectively, and 13,200 and 32,200 with chronic HCV, respectively. The number of IDUs developing HCV-related decompensated cirrhosis in Scotland is estimated to double between 2000 and 2020. As many as 16% and 27% of former IDUs in 2005 aged 30-39 and 40-49 years, respectively, were estimated to have moderate disease, which highlights the potential benefit of targeting HCV testing at former IDUs who belong to these age groups.
In conclusion
, the identification and treatment of a larger proportion of former IDUs with HCV disease and education about the importance of minimal alcohol consumption are needed to help achieve a greater impact on the future morbidity and mortality of this disease. (Hepatology 2005;42:711–723.)
Isatoribine, an Agonist of TLR7, Reduces Plasma Virus Concentration in Chronic Hepatitis C Infection *
Authors: Horsmans Yves , Berg Thomas , Desager Jean-Pierre , Mueller Tobias , Schott Eckart , Fletcher Simon P. , Steffy Kevin R. , Bauman Lisa A. , Kerr Bradley M. , Averett Devron R. 
Published: August 2005

Abstract

Immune-based therapy is the mainstay treatment for chronic hepatitis C virus (HCV) infection but causes multiple side effects and achieves durable viral clearance in only approximately 50% of patients. Most new investigational anti-HCV compounds are direct-acting antivirals for which durability of response and risk of viral mutations and resistance are not yet known. Therefore, continuing discovery and development of new immune-based treatments is desirable. Toll-like receptors (TLRs) are pathogen recognition receptors that initiate the innate immune response. The responsiveness of HCV or other ongoing chronic systemic infections to treatment with a selective TLR agonist has not been reported. Isatoribine is a selective agonist of TLR7. In a proof-of-concept study, we found that once-daily 7-day treatment with intravenous isatoribine 800 mg caused a significant (

P

= .001) reduction of plasma HCV RNA (mean, −0.76; range, −2.85 to +0.21 log10 units) in otherwise untreated patients (n = 12) who were chronically infected with HCV. Viral load reduction occurred in patients infected with genotype 1 as well as non-genotype 1 HCV. The reduction of viral load was correlated with induction of markers of a heightened immune antiviral state, including 2′-, 5′- oligoadenylate synthetase levels in whole blood. This treatment was well tolerated, with a low frequency of mild to moderate adverse events.
In conclusion,
systemic administration of the selective TLR7 agonist isatoribine resulted in dose-dependent changes in immunologic biomarkers and a statistically significant antiviral effect with relatively few and mild side effects. (Hepatology 2005;42:724–731.)
Telomere Shortening Correlates With Increasing Aneuploidy of Chromosome 8 in Human Hepatocellular Carcinoma *
Authors: Plentz Ruben R. , Schlegelberger Brigitte , Flemming Peer , Gebel Michael , Kreipe Hans , Manns Michael P. , Rudolph Lenhard K. , Wilkens Ludwig 
Published: August 2005

Abstract

Chromosomal instability (CIN) leads to an increase in aneuploidy and chromosomal aberrations in human hepatocellular carcinoma (HCC). Telomere shortening appears as one mechanism fostering the development of CIN. Whether telomere shortening correlates to specific genetic changes that characterize a certain type of cancer has yet to be established. In our recent study, we combined on a cellular level the analysis of hepatocellular telomere fluorescent intensity (TFI) and copy number of chromosome 8—one of the hallmark chromosomal alterations in hepatocellular carcinoma (HCC). We investigated 15 cytological fine-needle biopsies of aneuploid HCC and 5 touch prints of cadaver livers without cancer. Hepatocyte-specific TFI and the measurement of centromere-specific probe for chromosome 8 were both performed by quantitative fluorescence

in situ

hybridization (qFISH) or FISH. Combined analysis of both methods (coFISH) allowed measurement of telomere length and chromosome 8 copy number on a single cell level. We observed that telomere shortening correlates significantly with increasing copy number of chromosome 8 in HCC on the cellular level. Above the level of 5 copies of chromosome 8 per nucleus, no further shortening of telomeres was found, indicating that telomeres had reached a critically short length at this stage of aneuploidy.
In conclusion
, our study gives direct evidence that telomere shortening is linked to a specific genetic alteration characteristic for human HCC. (Hepatology 2005;42:522–526.)
Function Follows Form: The Structure of the N-Terminal Domain of HCV NS5A *
Authors: Moradpour Darius , Brass Volker , Penin Francois 
Published: August 2005

Abstract

Hepatitis C virus (HCV) is a human pathogen affecting nearly 3% of the world's population. Chronic infections can lead to cirrhosis and liver cancer. The RNA replication machine of HCV is a multi-subunit membrane-associated complex. The nonstructural protein NS5A is an active component of HCV replicase, as well as a pivotal regulator of replication and a modulator of cellular processes ranging from innate immunity to dysregulated cell growth. NS5A is a large phosphoprotein (56-58 kd) with an amphipathic α-helix at its amino terminus that promotes membrane association. After this helix region, NS5A is organized into 3 domains. The N-terminal domain (domain I) coordinates a single zinc atom per protein molecule. Mutations disrupting either the membrane anchor or zinc binding of NS5A are lethal for RNA replication. However, probing the role of NS5A in replication has been hampered by a lack of structural information about this multifunctional protein. Here we report the structure of NS5A domain I at 2.5-Å resolution, which contains a novel fold, a new zinc-coordination motif, and a disulfide bond. We use molecular surface analysis to suggest the location of protein-, RNA-, and membrane-interaction sites.
A physically based distributed subsurface–surface flow dynamics model for forested mountainous catchments
Authors: Mulungu Deogratias M. M. , Ichikawa Yutaka , Shiiba Michiharu 
Published: August 2005

AbstractThis study was designed to develop a physically based hydrological model to describe the hydrological processes within forested mountainous river basins. The model describes the relationships between hydrological fluxes and catchment characteristics that are influenced by topography and land cover. Hydrological processes representative of temperate basins in steep terrain that are incorporated in the model include intercepted rainfall, evaporation, transpiration, infiltration into macropores, partitioning between preferential flow and soil matrix flow, percolation, capillary rise, surface flow (saturation‐excess and return flow), subsurface flow (preferential subsurface flow and baseflow) and spatial water‐table dynamics. The soil–vegetation–atmosphere transfer scheme used was the single‐layer Penman–Monteith model, although a two‐layer model was also provided. The catchment characteristics include topography (elevation, topographic indices), slope and contributing area, where a digital elevation model provided flow direction on the steepest gradient flow path. The hydrological fluxes and catchment characteristics are modelled based on the variable source‐area concept, which defines the dynamics of the watershed response. Flow generated on land for each sub‐basin is routed to the river channel by a kinematic wave model. In the river channel, the combined flows from sub‐basins are routed by the Muskingum–Cunge model to the river outlet; these comprise inputs to the river downstream. The model was applied to the Hikimi river basin in Japan. Spatial decadal values of the normalized difference vegetation index and leaf area index were used for the yearly simulations. Results were satisfactory, as indicated by model efficiency criteria, and analysis showed that the rainfall input is not representative of the orographic lifting induced rainfall in the mountainous Hikimi river basin. Also, a simple representation of the effects of preferential flow within the soil matrix flow has a slight significance for soil moisture status, but is insignificant for river flow estimations. Copyright © 2005 John Wiley & Sons, Ltd.
Soil moisture states, lateral flow, and streamflow generation in a semi‐arid, snowmelt‐driven catchment
Authors: McNamara James P. , Chandler David , Seyfried Mark , Achet Shiva 
Published: August 2005

AbstractHydraulic connectivity on hillslopes and the existence of preferred soil moisture states in a catchment have important controls on runoff generation. In this study we investigate the relationships between soil moisture patterns, lateral hillslope flow, and streamflow generation in a semi‐arid, snowmelt‐driven catchment. We identify five soil moisture conditions that occur during a year and present a conceptual model based on field studies and computer simulations of how streamflow is generated with respect to the soil moisture conditions. The five soil moisture conditions are (1) a summer dry period, (2) a transitional fall wetting period, (3) a winter wet, low‐flux period, (4) a spring wet, high‐flux period, and (5) a transitional late‐spring drying period. Transitions between the periods are driven by changes in the water balance between rain, snow, snowmelt and evapotranspiration. Low rates of water input to the soil during the winter allow dry soil regions to persist at the soil–bedrock interface, which act as barriers to lateral flow. Once the dry‐soil flow barriers are wetted, whole‐slope hydraulic connectivity is established, lateral flow can occur, and upland soils are in direct connection with the near‐stream soil moisture. This whole‐slope connectivity can alter near‐stream hydraulics and modify the delivery of water, pressure, and solutes to the stream. Copyright © 2005 John Wiley & Sons, Ltd.
The historical and palaeoflood record of Katherine river, northern Australia: evaluating the likelihood of extreme discharge events in the context of the 1998 flood
Authors: Sandercock Peter , Wyrwoll Karl‐Heinz 
Published: August 2005

AbstractThe discharge regimes of the large rivers of northern Australia are characterized by the occurrence of extreme flood events with far‐reaching environmental and societal impacts. In January 1998 the largest flood ever recorded on the Katherine River, northern Australia, resulted in widespread inundation and resultant damage to the town of Katherine. The occurrence of the flood emphasized the unreliability of the then available flood probability estimates and prompted a palaeoflood approach to estimate the recurrence interval of the event. The location of Katherine is ideal for such a study, as the town is located immediately downstream from Katherine Gorge, which provides the necessary bedrock‐confined channel required for such an approach. In addition, previous work in Katherine Gorge had demonstrated that the gorge sections hold suitable deposits for palaeoflood stage reconstruction. The results of the present study show that at least two flow events with discharges similar to the 1998 flood have occurred within the last 600 years, and that high‐magnitude floods are a general feature of the discharge record of the Katherine River over the last c. 2000 years. Furthermore, because the study was undertaken within a few months of the occurrence of the 1998 flood, it provided the opportunity to evaluate the previously obtained flood discharge estimates and draw attention to the general uncertainties associated with palaeoflood studies. Our results emphasize that palaeoflood stage estimates based on slackwater deposits need to be treated as conservative estimates only. More specifically, with respect to the 1998 event, our study demonstrates that the controls of flood peak were more complex than simply flood routing through the gorge sections. It is clear that the areas downstream from Katherine Gorge made an important contribution to the flood peak of the 1998 event. Copyright © 2005 John Wiley & Sons, Ltd.
The great Atacama flood of 2001 and its implications for Andean hydrology
Authors: Houston John 
Published: August 2005

AbstractIn February 2001, widespread flooding occurred throughout the Atacama Desert of northern Chile and southern Peru. It was particularly severe in the Río Loa basin, where roads and bridges were disrupted and the town of Calama inundated. The instantaneous peak flow in the Río Salado, a tributary of the Río Loa, reached 310 m3 s−1, an order of magnitude higher than any previously recorded event. The flood is estimated to have a return period of 100–200 years and is shown to have been caused by intense, long‐duration rainfall in the western Cordillera associated with La Niña. The surface water response is typical of arid areas and highly dependent on antecedent conditions, but is quite different in perennial and ephemeral catchments. Ephemeral flood flows suffer high transmission losses, recharging phreatic aquifers. Perennial rivers have lower runoff coefficients, but baseflow levels remained high after the event for several months due to bank storage rebound and interflow. Extremely high energies of ∼3000 W m−2 were generated by the floods in the Cordillera, becoming less in the Precordillera and downstream. Erosion and sediment transport were consequently highest in the upper and middle reaches of the rivers, with mixed erosion‐deposition in the lowest reach. The new insights gained from the interpretation and quantification of this event have important implications for palaeoenvironmental analysis, hazard management, water resource evaluation and the palaeohydrological evolution of the Andes. Copyright © 2005 John Wiley & Sons, Ltd.
Comparative anatomical study of the autonomic cardiac nervous system in macaque monkeys
Authors: Kawashima Tomokazu , Sato Kenji , Akita Keiichi , Sasaki Hiroshi 
Published: August 2005

AbstractThe main aim of this study was to clarify the general morphology of the autonomic cardiac nervous system in macaque monkeys. A submacroscopic comparative anatomical study of the autonomic cardiac nervous system was performed by examining 22 sides of 11 bodies of four species of macaque monkeys, including some previously unreported species (pig‐tailed and stump‐tailed monkeys), under a surgical stereomicroscope. The following results were obtained. 1) The basic arrangement of the autonomic cardiac nervous system is constant in all examined macaques. 2) A superior cardiac nerve originating from the superior cervical ganglion was not observed, whereas the thoracic cardiac nerve originating from the sympathetic trunk/ganglia under the cervicothoracic ganglion was rarely observed in all the examined macaques. 3) The main cardiac nerve is the middle cardiac nerve originating from the middle cervical ganglion, similar to the situation in humans. 4) Although the superior, inferior, and thoracic cardiac branches of the vagus nerve were consistently observed, the left thoracic cardiac branch is rarely absent because of its lower origin to the heart. 5) The cranial autonomic nerves tend to distribute into the heart medially (arterial porta), and the caudal autonomic nerves tend to distribute into the heart laterally (venous porta). To comprehend the comparative morphological and evolutionary changes more completely, these results were compared with our previous studies and some references. Consequently, differences in the sympathetic cardiac nerves of macaques and humans are recognized, in spite of the similar morphologies of the vagal cardiac branches. These differences include the composition of the cervicothoracic ganglion, the lower positions of the middle cervical and cervicothoracic ganglia, and the narrow range for the origin of the cardiac nerves in macaques compared to that in humans. J. Morphol. © 2005 Wiley‐Liss, Inc.
Structural characterization of chelator‐terminated dendrimers and their synthetic intermediates by mass spectrometry
Authors: Ch. Berndt Ursula E. , Zhou Tao , Hider Robert C. , Liu Zu D. , Neubert Hendrik 
Published: August 2005

AbstractHerein, we report the structural analysis of a novel family of iron‐chelating dendrimers and their synthetic intermediates utilizing matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) and electrospray ionization ion trap (ESI IT) MS. These dendrimers share a benzene tricarbonyl core moiety attached to three tripodal branching units, each linking to three terminal groups, ranging from carboxyl, catechol and 3‐hydroxy‐6‐methyl‐pyran‐4‐one moieties and their protected analogs. In order to monitor the progression of dendrimer synthesis, all intermediates and final products were mass analyzed by conventional MALDI‐TOF MS with and without alkali metal spiking. For structural characterization, interpretable post‐source decay (PSD) and electrospray ionization ion trap MS/MS spectra were obtained from proton, sodium and potassium adducts of the dendrimers. One major route of dendrimer fragmentation was at or adjacent to the amide bonds either of the terminal chelating groups or near the core moiety. Fragmentation in the latter case was primarily at the N‐terminal side of the amide bond and was directed by the proximity of a tertiary carbon of the branching unit. Furthermore, it was found that terminal ester, ether and amide linkages to the protecting and chelating groups could be sequentially broken in a single MS/MS spectrum through multiple cleavages resulting in product ions of decreasing intensity. Moreover, such cleavages could also be induced in a stepwise manner in a multistage ion trap MSnexperiment. Copyright © 2005 John Wiley & Sons, Ltd.
Variable low‐mass filtering using an electrodynamic ion funnel
Authors: Page Jason S. , Tolmachev Aleksey V. , Tang Keqi , Smith Richard D. 
Published: August 2005

AbstractAn adjustable low‐mass filter has been developed for an electrospray ionization (ESI) source to block ions associated with unwanted background species from entering the mass spectrometer. The low‐mass filter is made by using an adjustable potential energy barrier from the conductance‐limiting plate of an electrodynamic ion funnel, which prohibits species with higher ion mobilities from exiting the ESI source. We show that this arrangement provides a linear voltage adjustment for low‐mass filtering from m/z 0 to 500. Mass filtering above m/z 500 is also performed; however, higher‐mass species are attenuated. The mass filter was tested with a liquid chromatography/mass spectrometry (LC/MS) analysis of a bovine serum albumin (BSA) tryptic digest and resulted in the ability to block low‐mass, background species, which accounted for 40–70% of the total ion current immediately behind the ESI source during peak elution and detection. Copyright © 2005 John Wiley & Sons, Ltd.
TRH‐like antidepressant peptide, pyroglutamyltyroslyprolineamide, occurs in rat brain
Authors: Eugene Pekary A. , Faull Kym F. , Paulson Mark , Lloyd Robert L. , Sattin Albert 
Published: August 2005

AbstractWe have previously reported the occurrence of pGlu‐Glu‐Pro‐NH2(Glu‐TRH, EEP), Val‐TRH, Tyr‐TRH, Leu‐TRH, Phe‐TRH, and Trp‐TRH in rat brain using a combination of HPLC and radioimmunoassays with antibodies that cross‐react with the general structure pGlu‐X‐Pro‐NH2 where ‘X’ maybe any amino acid residue (Peptides 2004; 25 : 647). This new family of TRH‐like peptides, along with TRH (pGlu‐His‐Pro‐NH2), has neuroprotective, anticonvulsant, antidepressant, euphoric, anti‐amnesic, and analeptic effects. We now report that a combination of affinity chromatography using a rabbit antibody specific for Tyr‐TRH and Phe‐TRH, along with HPLC and tandem mass spectrometry operating in the multiple reaction monitoring (MRM) mode, provide conclusive evidence for the presence of Tyr‐TRH in rat brain. Furthermore, synthetic Tyr‐TRH is active in the Porsolt Swim Test suggesting that it is a fourth member of this family of in vivo neuroregulatory agents that have psychopharmacotherapeutic properties. Copyright © 2005 John Wiley & Sons, Ltd.
Novel Photobleachable Deep UV Resists Based on Single Component Nonchemically Amplified Resist System
Authors: Kim Jin‐Baek , Kim Kyoung‐Seon 
Published: August 2005

AbstractSummary: Photobleachable deep UV resists were designed by introducing diazoketo groups in polymer side chains. The diazoketo groups undergo the Wolff rearrangement upon irradiation in the deep UV, affording ketenes that react with water to provide base‐soluble photoproducts. The polymers were synthesized by radical copolymerization of 2‐(2‐diazo‐3‐oxo‐butyryloxy)‐ethyl methacrylate, 2‐hydroxyethyl methacrylate, and γ‐butyrolacton‐2‐yl methacrylate. The single component resist showed 0.7 µm line and space patterns using a mercury‐xenon lamp in a contact printing mode.Scanning electron micrograph of 0.7 µm line and space patterns printed with polymer B at a dose of 70 mJ · cm−2.imageScanning electron micrograph of 0.7 µm line and space patterns printed with polymer B at a dose of 70 mJ · cm−2.