bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attenuation of PTEN increases p21 stability and cytosolic localization in kidney cancer cells: a potential mechanism of apoptosis resistance
Authors: Lin Pei-Yin , Fosmire Susan P , Park See-Hyoung , Park Jin-Young , Baksh Shairaz , Modiano Jaime F , Weiss Robert H 
Published: February 2007

Abstract

Background
The PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten) tumor suppressor gene is frequently mutated or deleted in a wide variety of solid tumors, and these cancers are generally more aggressive and difficult to treat than those possessing wild type PTEN. While PTEN lies upstream of the phosphoinositide-3 kinase signaling pathway, the mechanisms that mediate its effects on tumor survival remain incompletely understood. Renal cell carcinoma (RCC) is associated with frequent treatment failures (~90% in metastatic cases), and these tumors frequently contain PTEN abnormalities.

Results
Using the ACHN cell line containing wild type PTEN, we generated a stable PTEN knockdown RCC cell line using RNA interference. We then used this PTEN knockdown cell line to show that PTEN attenuation increases resistance to cisplatin-induced apoptosis, a finding associated with increased levels of the cyclin kinase inhibitor p21. Elevated levels of p21 result from stabilization of the protein, and they are dependent on the activities of phosphoinositide-3 kinase and Akt. More specifically, the accumulation of p21 occurs preferentially in the cytosolic compartment, which likely contributes to both cell cycle progression and resistance to apoptosis.

Conclusion
Since p21 regulates a decision point between repair and apoptosis after DNA damage, our data suggest that p21 plays a key role in mechanisms used by PTEN-deficient tumors to escape chemotherapy. This in turn raises the possibility to use p21 attenuators as chemotherapy sensitizers, an area under active continuing investigation in our laboratories.
Effects of Total Thyroid Ablation Versus Near-Total Thyroidectomy Alone on Mild to Moderate Graves’ Orbitopathy Treated with Intravenous Glucocorticoids
Authors: Menconi Francesca , Marinò Michele , Pinchera Aldo , Rocchi Roberto , Mazzi Barbara , Nardi Marco , Bartalena Luigi , Marcocci Claudio 
Published: February 2007

Abstract
Context: Graves’ orbitopathy (GO) is probably caused by autoimmune reactions against autoantigen(s) shared by thyroid and orbital tissues sustained by intrathyroidal autoreactive T-lymphocytes infiltrating the orbit. Total thyroid ablation (TTA) may be beneficial for GO through removal of shared antigen(s) and autoreactive T-lymphocytes, but randomized studies are lacking.
Objective: Our objective was to evaluate the effects of TTA in patients with GO treated with iv glucocorticoids (GC).
Design/Setting: A prospective, single-blind, randomized study was conducted at a referral center.
Patients/Interventions: Sixty patients with mild to moderate GO were randomized into: 1) near-total thyroidectomy (TX); or 2) TX plus 131I (TTA) groups, and then treated with iv GC. Patients were evaluated 3 and 9 months after iv GC.
Main Outcome Measure: Overall improvement of GO at 9 months was the main outcome measure.
Results: The distribution of GO outcome at 9 months was significantly more favorable in TTA than in TX patients (P = 0.0014 by χ2 test). A cumulative significant (P = 0.0054) difference between the two groups at 3 and 9 months was found using a generalized linear model. Radioiodine uptake test and thyroglobulin assay in a patient sample showed complete ablation in the majority of TTA, but not of TX patients.
Conclusions: Compared with thyroidectomy alone, TTA is followed by a better outcome of GO in patients given iv GC. Whether TTA maintains this advantage in the long-term remains to be established.
Infectious Diseases: Pharmacologic Treatment Options for Nosocomial Pneumonia Involving Methicillin-Resistant Staphylococcus aureus
Authors: Maclayton Darego O , Hall Ronald G 
Published: February 2007

Objective: To discuss current and potential treatment options for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). Data Sources: A MEDLINE search (1966–January 2007) was conducted to identify English-language literature on pharmacotherapy of nosocomial pneumonia and the bibliographies of pertinent articles. Programs and abstracts from infectious disease meetings were also searched. Search terms included MRSA, nosocomial pneumonia, pulmonary infections, vancomycin, quinupristin/dalfopristin, linezolid, daptomycin, tigecycline, dalbavancin, oritavancin, and ceftobiprole. Data Selection and Data Extraction: All articles were critically evaluated and all pertinent information was included in this review. Data Synthesis: Vancomycin has been the drug of choice for MRSA infections for many years. Recent data suggest that linezolid may be superior to vancomycin in the treatment of MRSA nosocomial pneumonia. However, there are limitations to the available data. Therefore, prospective, randomized studies are needed before linezolid is recommended as the preferred first-line therapy. Other approved agents for nosocomial MRSA infections, such as quinupristin/dalfopristin and daptomycin, should not be used in the treatment of MRSA pneumonia, as they were inferior in clinical trials. Tigecycline has excellent activity against MRSA in vitro, but should not be routinely used for the treatment of MRSA pneumonia, as clinical data are lacking. In a Phase III clinical trial, an anti-MRSA cephalosporin, ceftobiprole, is being evaluated for effectiveness against nosocomial pneumonia. Investigational glycopeptides may eventually have a role in the treatment of nosocomial pneumonia, but data are currently lacking. Conclusions: Vancomycin is still the drug of choice for treatment of MRSA pneumonia, and linezolid should be used as an alternative agent. Linezolid should carry strong consideration for patients with vancomycin-induced nephrotoxicity or a documented lack of response to vancomycin. Tigecycline and investigational agents with activity against MRSA may be future options for nosocomial pneumonia due to MRSA.
Bisphosphonate-Induced Osteonecrosis of the Jaw
Authors: Krueger Courtney D , West Patricia M , Sargent Matthew , Lodolce Amy E , Pickard A Simon 
Published: February 2007

Objective: To review the risk of osteonecrosis of the jaw associated with bisphosphonates. Data Sources: A MEDLINE search (1966–January 2007) and a search of international Pharmaceutical Abstracts (1970–January 2007) were conducted to identify relevant literature. Additional references were reviewed from selected articles. Study Selection and Data Extraction: Articles related to bisphosphonate-induced osteonecrosis of the jaw were reviewed and summarized. Inclusion criteria required that articles be either case studies or case series that were reporting actual cases linking osteonecrosis of the jaw with bisphosphonate use. Articles that addressed sites of osteonecrosis not involving the jaw, teaching cases (fictitious patients), and a retrospective claims analysis paper were excluded from consideration. Data Synthesis: Bisphosphonates have recently been linked to osteonecrosis of the jaw, with the greatest incidence seen with the intravenous preparations zoledronic acid and pamidronate. Osteonecrosis refers to death of a part of the bone, resulting in decreased bone density. Although the majority of occurrences have been associated with the intravenous bisphosphonates, oral bisphosphonates have also been implicated. Other risk factors noted from reported cases include dental extraction or trauma to the jaw exposing part of the bone. It is difficult to determine an exact incidence of osteonecrosis of the jaw in the general population of patients prescribed bisphosphonates; however, the incidence in cancer patients is approximately 6–7%. Conclusions: Although discontinuation of intravenous bisphosphonates in cancer patients has been recommended, stopping oral bisphosphonates prior to dental work cannot be universally endorsed at this time, since it is unknown whether this is effective in reducing the risk of osteonecrosis of the jaw. Treatment of this condition is not well established; therefore, efforts should be directed toward prevention. Pharmacists may further counsel patients to practice good oral hygiene and regularly follow up with their dentist during therapy. Current evidence suggests limited surgical debridement with systemic and local antibiotics as treatments.
Cortical Control of Zona Incerta
Authors: Barthó Péter , Slézia Andrea , Varga Viktor , Bokor Hajnalka , Pinault Didier , Buzsáki György , Acsády László 
Published: February 2007

The zona incerta (ZI) is at the crossroad of almost all major ascending and descending fiber tracts and targets numerous brain centers from the thalamus to the spinal cord. Effective ascending drive of ZI cells has been described, but the role of descending cortical signals in patterning ZI activity is unknown.Cortical control over ZI function was examined during slow cortical waves (1–3 Hz), paroxysmal high-voltage spindles (HVSs), and 5–9 Hz oscillations in anesthetized rats. In all conditions, rhythmic cortical activity significantly altered the firing pattern of ZI neurons recorded extracellularly and labeled with the juxtacellular method. During slow oscillations, the majority of ZI neurons became synchronized to the depth-negative phase (“up state”) of the cortical waves to a degree comparable to thalamocortical neurons. During HVSs, ZI cells displayed highly rhythmic activity in tight synchrony with the cortical oscillations. ZI neurons responded to short epochs of cortical 5–9 Hz oscillations, with a change in the interspike interval distribution and with an increase in spectral density in the 5–9 Hz band as measured by wavelet analysis. Morphological reconstruction revealed that most ZI cells have mediolaterally extensive dendritic trees and very long dendritic segments. Cortical terminals established asymmetrical synapses on ZI cells with very long active zones.These data suggest efficient integration of widespread cortical signals by single ZI neurons and strong cortical drive. We propose that the efferent GABAergic signal of ZI neurons patterned by the cortical activity can play a critical role in synchronizing thalamocortical and brainstem rhythms.
Toxicity ranking of estuarine sediments on the basis of Sparus aurata biomarkers
Authors: Cunha Isabel , Neuparth Teresa , Caeiro Sandra , Costa Maria Helena , Guilhermino Lúcia 
Published: February 2007

Abstract
Sparus aurata biomarkers were used to rank sediments from the Sado River estuary (Portugal) according to their toxicity. Initially, the activities of liver ethoxyresorufin-O-deethylase, liver and gill glutathione S-transferases, muscle lactate dehydrogenase, and brain acetylcholinesterase were tested in a laboratory bioassay with the reference compound benzo[a]pyrene. Enzymatic activities were determined in different tissues of fish exposed for 48, 96, or 240 h to three concentrations of benzo[a]pyrene (25, 50, and 100 μg/L). Induction of liver ethoxyresorufin-O-deethylase was observed at all the exposure periods and concentrations, suggesting a continuous response of this system to toxicant exposure. Induction of liver glutathione S-transferases activity was only observed after 240 h of exposure, whereas gill glutathione S-transferases activity was significantly inhibited at all the exposure periods, suggesting a direct or indirect effect of the toxicant on these enzymes. Inhibition of lactate dehydrogenases activity was only observed after 96 h of exposure to 25 μg/L of benzo[a]pyrene. No significant effects were observed on acetylcholinesterase activity, suggesting that cholinergic function of S. aurata is not affected by benzo[a]pyrene. In a second phase, fish were exposed for 240 h to sediments collected at five sites of the Sado River estuary, and the same biomarkers were analyzed. For all the enzymes assayed, significant differences among sites were found. In this study, the battery of biomarkers used allowed to discrimination among sites with different types of contamination, levels of contamination, or both, after multivariate data analysis. Discrimination of sites was similar to the ranking provided by a more complex and parallel study (including chemical analysis of sediments, macrobenthic community analysis, amphipod mortality toxicity tests, and sea urchin abnormality embryo assays), suggesting its suitability to evaluate the toxicity of estuarine sediments.
Mercury-selenium association in antarctic seal hairs and animal excrements over the past 1,500 years
Authors: Yin Xuebin , Sun Liguang , Zhu Renbin , Liu Xiaodong , Ruan Diyun , Wang Yuhong 
Published: February 2007

Abstract
Strong positive correlations between selenium (Se) and total mercury (HgT) contents in the liver of marine mammals and mercury mine workers in modern times have been documented in numerous investigations. Herein, we report a positive correlation between Se and HgT concentrations over the past 1,500 years in the seal hairs and in the lake sediments amended by seal or penguin excrements on King George Island (63°23′S, 57°00′W), West Antarctica. Because the changes in the input of Se and Hg into the marine environments of the studied sites do not seem to be synchronous, this striking correlation indicates a self-protection mechanism in Antarctic seals and penguins: Every time there is heavier Hg burden, more Se is accumulated to reduce the toxicity of Hg. This positive correlation between Hg and Se contents in the seal hairs and excrement sediments, however, becomes insignificant in the recent 50 years for unknown reasons.
Aryl hydrocarbon bioaccessibility to small mammals from arctic plants using in vitro techniques
Authors: Armstrong Sarah A. , Van de Wiele Tom , Germida James J. , Siciliano Steven D. 
Published: February 2007

Abstract
Through their diet, herbivores inhabiting contaminated sites may be chronically exposed to a variety of aryl hydrocarbons (e.g., dioxins and polycyclic aromatic hydrocarbons [PAHs]). However, little is known about how differences in morphology and physiology among plant species alter the environmental accumulation of aryl hydrocarbons or their release and subsequent activity in the gastrointestinal tract of herbivores after ingestion. In the present study, the activity of aryl hydrocarbons during digestion was examined using six Arctic plant species growing in impacted and reference sites near Inuvik, Northwest Territories, Canada. The plant species studied were black spruce (Picea mariana), labrador tea (Ledum groenlandicum), bog birch (Betula glandulosa), green alder (Alnus crispa), water sedge (Carex aquatilis), and little-tree willow (Salix arbusculoides). Plants were digested using a simulator of the upper digestive tract, and aryl hydrocarbon release was evaluated using an aryl hydrocarbon-receptor assay. Bioaccessible aryl hydrocarbon activity varied among the plant species tested. The species with the greatest activity was green alder, and the species with the least activity was black spruce. Further investigation revealed that digested plant extracts may antagonize the aryl hydrocarbon receptor and prevent bioactivation of the aryl compound benzo[a]pyrene. Thus, PAH risk from the ingestion of vegetation varies among plant species and may depend on antagonists present in the vegetation.
Bioaccumulation, oxidative stress, and neurotoxicity in Danio rerio exposed to different isotopic compositions of uranium
Authors: Barillet Sabrina , Adam Christelle , Palluel Olivier , Devaux Alain 
Published: February 2007

Abstract
Experiments were carried out on adult male zebrafish (Danio rerio) to assess early changes induced by waterborne exposure to different isotopic compositions of uranium (depleted uranium associated or not with 233U). Oxidative stress and neurotoxicity were selected as effect endpoints to characterize uranium chemo- and radiotoxicity. Catalase, glutathione peroxidase, and superoxide dismutase activities and total glutathione content of hepatic extracts, as well as brain acetylcholinesterase activity and uranium bioaccumulation, were measured. Oxidative stress induced by uranium exposure led to decreases in superoxide dismutase and catalase activity levels as well as total glutathione content in liver extracts. These perturbations were significantly more marked in 233U-exposed fish. Furthermore, significant increase in acetylcholinesterase activity was observed in brain extracts at the same level, whatever the isotopic composition of uranium.
A predictive quantitative structure-activity relationship model for the photoinduced toxicity of polycyclic aromatic hydrocarbons toDaphnia magnawith the use of factors for photosensitization and photomodification
Authors: Lampi Mark A. , Gurska Jolanta , Huang Xiao-Dong , Dixon D. George , Greenberg Bruce M. 
Published: February 2007

AbstractPolycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants that readily absorb environmentally relevant solar ultraviolet radiation. On absorption of a photon, photoinduced toxicity of PAHs is manifested through photosensitization and photomodification. Both of these processes occur under environmentally relevant levels of actinic radiation. An empirical quantitative structure—activity relationship model previously developed was explanatory of photoinduced toxicity of 16 PAHs in Lemna gibba (duckweed). This model was found to be predictive of toxicity to Vibrio fischeri. The L. gibba quantitative structure-activity relationship showed that a photosensitization factor and a photomodification factor could be combined to describe photoinduced toxicity. To further examine this model, we assessed whether it could be applied to Daphnia magna (water flea), a key bioindicator species in aquatic ecosystems. Toxicity was assessed as median effective concentration and median effective time for immobility. As with L. gibba and V. fischeri, neither the photosensitization factor nor the photomodification factor alone correlated to toxicity in D. magna. However, a photosensitization factor modified for D. magna exhibited a correlation to toxicity (r2 = 0.86), which was modestly improved when summed with a modified photomodification factor (r2 = 0.92). The greatest correlation was observed with median effective concentration data. This research provides evidence that models incorporating factors for photosensitization and photomodification have interspecies applicability.
Induction and metal speciation of metallothionein in wood mice (Apodemus sylvaticus) along a metal pollution gradient
Authors: Rogival Damien , Van Campenhout Karen , Infante Heidi Goenaga , Hearn Ruth , Scheirs Jan , Blust Ronny 
Published: February 2007

Abstract
We investigated the binding of Cd, Cu, and Zn to metallothionein (MT) and other metal-binding proteins in free-living wood mice (Apodemus sylvaticus L.) captured in four areas along a metal pollution gradient. We measured total and cytosolic Cd, Cu, and Zn concentrations in mouse liver and kidney by means of inductively coupled plasma—mass spectrometry (ICP-MS). Total (Cu, Cd, Zn)-MT levels were determined in the same tissues by means of the cadmium thiomolybdate saturation assay. Metal speciation of metalloproteins was studied by means of size-exclusion high-performance liquid chromatography-ICP-MS. Liver and kidney of wood mice from the site adjacent to the pollution source showed the highest Cd and Zn concentrations (total and cytosolic) and (Cu, Cd, Zn)-MT levels compared to the other sites farther away from the pollution source. No or only small site differences in tissue Cu concentrations were observed. Almost all the variation (85–95%) in hepatic and renal (Cu, Cd, Zn)-MT levels was explained by the total or cytosolic hepatic Zn and Cd concentration or the renal Cd concentration, respectively. An analysis of the cytosolic metal speciation showed that the Cd-MT, Cu-MT, and Zn-MT fractions in liver and kidney increased significantly with increasing cytosolic metal concentrations. Metals associated with the other cytosolic protein fractions did not increase with increasing exposure. These results illustrate the important role of MT in metal homeostasis and detoxification processes. We conclude that MT is a useful biomarker for environmental metal contamination in free-living wood mice.
On the properties of equations of state at infinite pressure
Authors: Brandani Stefano , Brandani Vincenzo 
Published: February 2007

AbstractUsing the exact solution valid for hard spheres in the proximity of infinite pressure, the correct limits for the compressibility (infinite), the residual Helmholtz energy (infinite), and the excess Helmholtz energy (finite) are derived. All the equations of state commonly used in chemical engineering applications fail to fulfil one of these limits, and are shown to be inconsistent in the limit of infinite pressure. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Dynamic model of a supercritical fluid extraction plant
Authors: Fernandes João , Ruivo Rui , Simões Pedro 
Published: February 2007

AbstractA dynamic model of a supercritical fluid extraction (SFE) process was developed and applied to the fractionation of the binary mixture squalene/methyl oleate by supercritical carbon dioxide. The model combines a mathematical model for each main piece of equipment of the SFE process, namely, the countercurrent packed extraction column, the separation column for oil recovery and solvent regeneration, the heat exchanger for heating fresh CO2, and the make‐up of solvent in the process plant. Experimental tests were performed in a pilot‐plant SFE apparatus where perturbations on prespecified operating parameters were induced and their effect on main process variables determined. A good agreement was obtained between experimental and predicted results. In addition, the dynamic model of the packed extraction column was applied to other SFE case studies where sufficient experimental data is available. The dynamic model was found to correctly predict the outlet streams composition profiles of all the case studies. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Community experience with bortezomib in patients with multiple myeloma
Authors: Onitilo Adedayo A. , Engel Jessica , Olatosi Bankole , Fagbemi Seth 
Published: February 2007

AbstractCommunity practice experience allows a nonselective care of patient using information derived from a more controlled clinical trial environment. We present our community experience with multiple myeloma patients with advanced age, long disease duration since diagnosis, advanced stage, multiple prior therapies including stem cell transplantation, co‐morbidities, and other poor prognostic features, such as low albumin, high B‐2 microglobulin, renal failure, and the presence of poor risk chromosomal abnormalities. Our response rates are comparable to those from clinical trials. Bortezomib is well tolerated in this population of multiple myeloma patients with the exception of infection adverse events that are generally mild grade 1–2. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.