bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of α2C‐adrenoceptors in the reduction of skin blood flow induced by local cooling in mice
Authors: Honda M , Suzuki M , Nakayama K , Ishikawa T 
Published: July 2007

Background and purpose:The reduction of skin blood flow induced by local cooling results from a reflex increase in sympathetic output and an enhanced vasoconstrictor activity of cutaneous vessels. The present study investigated the latter local response in vivo in tetrodotoxin‐treated mice, in which the sympathetic nerve tone was abolished.Experimental approach:Male ddY mice, anaesthetized with pentobarbitone, were treated with tetrodotoxin and artificially ventilated. The plantar skin blood flow (PSBF) was measured by laser Doppler flowmetry.Key results:Cooling the air temperature around the left foot from 25 to 10°C decreased the PSBF of the left foot. Bunazosin, an α1‐adrenoceptor antagonist, RS79948, an α2‐adrenoceptor antagonist, and MK‐912, an α2C‐adrenoceptor antagonist, all significantly inhibited the cooling‐induced reduction of PSBF; the inhibition by bunazosin was relatively small compared with that by RS79948 and MK‐912. The response was not affected by guanethidine or bretylium, but was diminished in adrenalectomized mice. An intra‐arterial injection of clonidine, an α2‐adrenoceptor agonist, to the left iliac artery of adrenalectomized mice caused a transient decrease in PSBF, which was significantly augmented at 10°C. MK‐912 suppressed only the augmented portion at 10°C. Y‐27632, H‐1152 and fasudil, Rho kinase inhibitors, also inhibited the cooling‐induced reduction of PSBF. RS79948 caused no further reduction of the cooling‐induced response after the inhibition by Y‐27632.Conclusions and implications:Local cooling‐induced reduction of skin blood flow in mice primarily results from increased reactivity of α2C‐adrenoceptors to circulating catecholamines, in which the Rho/Rho kinase pathway is involved.British Journal of Pharmacology (2007) 152, 91–100; doi:10.1038/sj.bjp.0707380
Rights theory in a specific healthcare context: “Speaking ill of the dead”
Authors: Wildfire Adrian , Stebbing Justin , Gazzard Brian 
Published: July 2007

Abstract
Generally physicians have a legal and ethical obligation of keeping confidentiality regarding their communication with patients and it is clear that we all have rights. The application of rights theorem, which usually refers to the recognition of individual human rights, to the deceased offers possible answers to the problematic question of patient confidentiality after death. Philosophical considerations broadly support utilitarian ideals concerning the ‘common good’. However, it may be possible to rank rights according to a hierarchy of need and thus preserve individual rights where they do not impinge upon the publics' right to protection from harm and the physician's right to tell the truth. This has broad implications for confidentiality, anonymity and health care information in general for patients, their families and healthcare workers. We discuss these issues, with specific reference to an individual case.
Management of overactive bladder syndrome
Authors: Srikrishna Sushma , Robinson Dudley , Cardozo Linda , Vella Maria 
Published: July 2007

Abstract
Overactive bladder (OAB) syndrome is the term used to describe the symptom complex of urinary urgency with or without urge incontinence, usually with frequency and nocturia. Drug treatment continues to have an important role in the management of women with OAB. Other treatment options include conservative management with lifestyle interventions, modification of fluid intake, and physiotherapy including bladder retraining. Surgery remains the last resort in the treatment and is usually reserved for intractable detrusor overactivity, as it is associated with significant morbidity. This article reviews the management of the overactive bladder with specific focus on newer developments in the medical treatment of OAB in women.
Corrosion Propagation Behavior of New Metallic Rebar Materials in Simulated Concrete Environments and Engineering Implications
Authors: Hurley Michael F. , Scully John 
Published: July 2007

The radial (depth) and lateral (length) corrosion propagation behavior of 316LN stainless steel, 2101 LDX duplex stainless steel, and MMFX-2 compared to plain carbon steel were characterized in saturated Ca(OH)2 with NaCl additions. Radial pit growth was ohmically controlled for all materials but repassivated more readily at high potentials in the case of 316LN and 2101 LDX stainless steels. Conversely, pit growth on carbon steel propagated at all applied anodic potentials and did not repassivate until deactivation by cathodic polarization. Stainless steel showed the highest resistance to lateral corrosion propagation from an active site during microelectrode array testing.	In contrast, carbon steel was found to easily undergo widespread depassivation along the surface compared to stainless steel. 2101 LDX duplex stainless and MMFX-2 showed similar radial propagation behavior and corrosion morphology, which was intermediate between carbon steel and 300 series type stainless steel.
Electrochemical Deposition of Manganese and Copper-Manganese Alloy on Silicon
Authors: Radisic Aleksandar , Hernandez Jose Luis , Tokei Zsolt , Beyer Gerald , Vereecken P. M. 
Published: July 2007

In this paper, we report on the electrochemical deposition of manganese and copper-manganese alloy on silicon from sulfate solutions with and without complexing agents. We show that the composition of copper-manganese films deposited on n-type (100) silicon can be controlled using different deposition parameters and bath compositions.	Manganese was deposited on p-type (100) silicon only from the simplest solutions, containing no copper and complexing agents.
2-Methoxy antimycin reveals a unique mechanism for Bcl-xL inhibition
Authors: Schwartz Pamela S. , Manion Michael K. , Emerson Christine B. , Fry John S. , Schulz Craig M. , Sweet Ian R. , Hockenbery David M. 
Published: July 2007

Abstract
Overexpression of Bcl-xL in multiple cancers correlates with resistance to chemotherapy and radiation therapy, and provides a rationale for development of small-molecule Bcl-xL inhibitors. Based on knockout studies, nonneoplastic cells also require Bcl-xL survival functions, particularly when challenged with cytotoxic agents. We analyze the selective cytotoxicity of one Bcl-xL inhibitor, 2-methoxy antimycin A, toward cells with excess exogenous Bcl-xL in isogenic cell line pairs. This selectivity, characteristic of a gain-of-function mechanism, is not shared by other known Bcl-xL inhibitors, including BH3I-2, HA14-1, ABT-737, gossypol, or the stapled BH3 helical peptide SAHB-BID. We show that Bcl-xL overexpression induces a shift in energy metabolism from oxidative phosphorylation to glycolysis. Treatment with 2-methoxy antimycin A acutely reverses the metabolic effects of Bcl-xL, causing mitochondrial hyperpolarization and a progressive increase in mitochondrial NAD(P)H. We identify an additional small-molecule Bcl-xL inhibitor, NSC 310343, establishing a class of Bcl-xL inhibitors with gain-of-function activity. In contrast to other Bcl-xL inhibitors, combining gain-of-function Bcl-xL inhibitors with a standard inducer of apoptosis, staurosporine, enhances selective cytotoxicity toward Bcl-xL–overexpressing cells. These results provide an example of the intersection of bioenergetic metabolism and Bcl-xL functions and suggest a metabolic basis for the gain-of-function mechanism of Bcl-xL inhibitors. [Mol Cancer Ther 2007;6(7):2073–80]
Regulation of mitosis via mitotic kinases: new opportunities for cancer management
Authors: Schmit Travis L. , Ahmad Nihal 
Published: July 2007

Abstract
Mitosis, a critical and highly orchestrated event in the cell cycle, decides how cells divide and transmit genetic information from one cell generation to the next. Errors in the choreography of these events may lead to uncontrolled proliferation, aneuploidy, and genetic instability culminating in cancer development. Considering the central role of phosphorylation in mitotic checkpoints, spindle function, and chromosome segregation, it is not surprising that several mitotic kinases have been implicated in tumorigenesis. These kinases play pivotal roles throughout cellular division. From DNA damage and spindle assembly checkpoints before entering mitosis, to kinetochore and centrosome maturation and separation, to regulating the timing of entrance and exit of mitosis, mitotic kinases are essential for cellular integrity. Therefore, targeting the mitotic kinases that control the fidelity of chromosome transmission seems to be a promising avenue in the management of cancer. This review provides an insight into the mechanism of mitotic signaling, especially the role of critical mitotic kinases. We have also discussed the possibilities of the use of mitotic kinases in crafting novel strategies in cancer management. [Mol Cancer Ther 2007;6(7):1920–31]
Inhibition of c-Src expression and activation in malignant pleural mesothelioma tissues leads to apoptosis, cell cycle arrest, and decreased migration and invasion
Authors: Tsao Anne S. , He Dandan , Saigal Babita , Liu Suyu , Lee J. Jack , Bakkannagari Srinivasa , Ordonez Nelson G. , Hong Waun Ki , Wistuba Ignacio , Johnson Faye M. 
Published: July 2007

Abstract
Malignant pleural mesothelioma (MPM) is a deadly disease with few systemic treatment options. One potential therapeutic target, the non–receptor tyrosine kinase c-Src, causes changes in proliferation, motility, invasion, survival, and angiogenesis in cancer cells and may be a valid therapeutic target in MPM. To test this hypothesis, we determined the effects of c-Src inhibition in MPM cell lines and examined c-Src expression and activation in tissue samples. We analyzed four MPM cell lines and found that all expressed total and activated c-Src. Three of the four cell lines were sensitive by in vitro cytotoxicity assays to the c-Src inhibitor dasatinib, which led to cell cycle arrest and increased apoptosis. Dasatinib also inhibited migration and invasion independent of the cytotoxic effects, and led to the rapid and durable inhibition of c-Src and its downstream pathways. We used immunohistochemical analysis to determine the levels of c-Src expression and activation in 46 archived MPM tumor specimens. The Src protein was highly expressed in tumor cells, but expression did not correlate with survival. However, expression of activated Src (p-Src Y419) on the tumor cell membrane was higher in patients with advanced-stage disease; the presence of metastasis correlated with higher membrane (P = 0.03) and cytoplasmic (P = 0.04) expression of p-Src Y419. Lower levels of membrane expression of inactive c-Src (p-Src Y530) correlated with advanced N stage (P = 0.02). Activated c-Src may play a role in survival, metastasis, and invasion of MPM, and targeting c-Src may be an important therapeutic strategy. [Mol Cancer Ther 2007;6(7):1962–72]
Preventive effects of Polyphenon E on urinary bladder and mammary cancers in rats and correlations with serum and urine levels of tea polyphenols
Authors: Lubet Ronald A. , Yang Chung S. , Lee Mao-Jung , Hara Yukihiko , Kapetanovic Izet M. , Crowell James A. , Steele Vernon E. , Juliana M. Margaret , Grubbs Clinton J. 
Published: July 2007

Abstract
Polyphenon E, a standardized mixture of green tea polyphenols, was examined for its chemopreventive efficacy against chemically induced urinary bladder and mammary cancers. In the present study, Polyphenon E was administered after the last dose of 4-hydroxybutyl(butyl)nitrosamine, or roughly 30% of the way into the experiment. Polyphenon E (100 or 250 mg/kg body weight/d) caused a dose-dependent decrease in palpable urinary bladder tumors [low dose, 14 of 34; high dose, 6 of 35; controls, 20 of 34 (P &lt; 0.01)]. In the mammary cancer model, Polyphenon E [333 or 1,000 mg/kg body weight (BW)/d] was administered beginning 5 days after a single dose of methylnitrosourea. In contrast to its significant efficacy in bladder tumor prevention, Polyphenon E had a minimal effect in the prevention of mammary cancers. Levels of polyphenols were determined in the urine and serum of rats. Relatively high levels of various polyphenols (and metabolites) were found in the urine. However, virtually no epigallocatechin-3-gallate was observed in the urine because of low systemic bioavailability; although it represents almost 65% of the polyphenols in Polyphenon E. Levels of polyphenols in serum were 50× to 1,000× less than were observed in urine. The bioavailability of these tea polyphenols to different organ sites may contribute to the differing preventive efficacy of Polyphenon E against urinary bladder and mammary cancers. [Mol Cancer Ther 2007;6(7):2022–8]
The HLA A*0201–restricted hTERT540–548 peptide is not detected on tumor cells by a CTL clone or a high-affinity T-cell receptor
Authors: Purbhoo Marco A. , Li Yi , Sutton Deborah H. , Brewer Joanna E. , Gostick Emma , Bossi Giovanna , Laugel Bruno , Moysey Ruth , Baston Emma , Liddy Nathaniel , Cameron Brian , Bennett Alan D. , Ashfield Rebecca , Milicic Anita , Price David A. , Classon Brendan J. , Sewell Andrew K. , Jakobsen Bent K. 
Published: July 2007

AbstractTumor-associated human telomerase reverse transcriptase (hTERT) is expressed in &gt;85% of human tumors but not in most normal cells. As a result, this antigen has received considerable attention from those interested in cancer immunotherapy. Specifically, there has been strong interest in MHC class I–associated peptides derived from hTERT because these are expressed on the cell surface and thus may enable the targeting of tumor cells. Much of this interest has focused on peptide 540–548, ILAKFLHWL, which was predicted to exhibit the strongest binding to the common HLA A*0201 presenting molecule. The hTERT540–548 peptide is currently being assessed in therapeutic vaccination trials; however, there is controversy surrounding whether it is naturally processed and presented on the surface of neoplastic cells. Here, we generate two highly sensitive reagents to assess the presentation of hTERT540–548 on tumor cells: (a) a CD8+ CTL clone, and (b) a recombinant T-cell receptor (TCR) that binds with picomolar affinity and a half-life exceeding 14 h. This TCR enables the identification of individual HLA A2-hTERT540–548 complexes on the cell surface. The use of both this TCR and the highly antigen-sensitive CTL clone shows that the hTERT540–548 peptide cannot be detected on the surface of tumor cells, indicating that this peptide is not a naturally presented epitope. We propose that, in future, rigorous methods must be applied for the validation of peptide epitopes used for clinical applications. [Mol Cancer Ther 2007;6(7):2081–91]
TRAIL therapy in non–small cell lung cancer cells: sensitization to death receptor–mediated apoptosis by proteasome inhibitor bortezomib
Authors: Voortman Jens , Resende Tatiana P. , Abou El Hassan Mohamed A.I. , Giaccone Giuseppe , Kruyt Frank A.E. 
Published: July 2007

AbstractActivation of the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) receptor pathway is a promising therapeutic strategy to selectively eradicate cancer cells, including non–small cell lung cancer (NSCLC) cells. Recombinant human (rh) TRAIL/Apo-2L, a TRAIL-encoding adenovirus, and monoclonal antibodies directed against TRAIL receptors R1 and R2 were used to study cytotoxicity of TRAIL therapy in NSCLC cells. NSCLC cells showed differential sensitivity to TRAIL therapy, regardless of the agent used. Combination treatment of bortezomib and rhTRAIL led to synergistic apoptosis induction in NSCLC cell lines. Enhancement of rhTRAIL-induced apoptosis by bortezomib was caspase dependent, implicating extrinsic as well as intrinsic apoptosis activation, as shown by increased processing of caspase-8 as well as caspase-9, and could be abrogated completely by overexpression of caspase-8 inhibitor cytokine response modifier A (CrmA), and partially by overexpression of Bcl-2. Enhanced surface expression of TRAIL-R2, but also TRAIL-R1, was associated with bortezomib treatment, which is likely to contribute to the increased processing of caspase-8 in the combination treatment. Furthermore, TRAIL-induced activation of prosurvival transcription factor nuclear factor-κB was prevented by cotreatment with bortezomib, which may contribute to the observed synergistic apoptosis induction. Our preclinical data indicate that combination therapy of TRAIL and bortezomib may be an effective strategy for NSCLC. [Mol Cancer Ther 2007;6(7):2103–12]
Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity
Authors: Kumar Rakesh , Knick Victoria B. , Rudolph Sharon K. , Johnson Jennifer H. , Crosby Renae M. , Crouthamel Ming-Chih , Hopper Teresa M. , Miller Charles G. , Harrington Laura E. , Onori James A. , Mullin Robert J. , Gilmer Tona M. , Truesdale Anne T. , Epperly Andrea H. , Boloor Amogh , Stafford Jeffrey A. , Luttrell Deirdre K. , Cheung Mui 
Published: July 2007

Abstract
With the development of targeted therapeutics, especially for small-molecule inhibitors, it is important to understand whether the observed in vivo efficacy correlates with the modulation of desired/intended target in vivo. We have developed a small-molecule inhibitor of all three vascular endothelial growth factor (VEGF) receptors (VEGFR), platelet-derived growth factor receptor, and c-Kit tyrosine kinases, pazopanib (GW786034), which selectively inhibits VEGF-induced endothelial cell proliferation. It has good oral exposure and inhibits angiogenesis and tumor growth in mice. Because bolus administration of the compound results in large differences in Cmax and Ctrough, we investigated the effect of continuous infusion of a VEGFR inhibitor on tumor growth and angiogenesis. GW771806, which has similar enzyme and cellular profiles to GW786034, was used for these studies due to higher solubility requirements for infusion studies. Comparing the pharmacokinetics by two different routes of administration (bolus p.o. dosing and continuous infusion), we showed that the antitumor and antiangiogenic activity of VEGFR inhibitors is dependent on steady-state concentration of the compound above a threshold. The steady-state concentration required for these effects is consistent with the concentration required for the inhibition of VEGF-induced VEGFR2 phosphorylation in mouse lungs. Furthermore, the steady-state concentration of pazopanib determined from preclinical activity showed a strong correlation with the pharmacodynamic effects and antitumor activity in the phase I clinical trial. [Mol Cancer Ther 2007;6(7):2012–21]
North-South Divisions in Multilateral Environmental Agreements: Negotiating the Private Sector's Role in Three Rio Agreements
Authors: Wagner Lynn 
Published: July 2007

AbstractThis article analyzes negotiations in the United Nations Commission on Sustainable Development, the Framework Convention on Climate Change, and the Convention to Combat Desertification and focuses on discussions related to technology transfers from the North to the South. These transfers and the financial flows that the private sector could bring with it are closely related to what was believed to be a bargain reached in 1992 at the Rio Earth Summit. During subsequent negotiations, delegates from developed and developing countries have followed a fairly predictable 'script' on these issues – developed countries generally insist that the private sector, as the owner of the technology, must be involved in its transfer, while developing countries have insisted the governments of developed countries should honor their past commitments and promote these transfers. This study describes the development of the script under the three negotiating bodies at Rio, examines the variables that have contributed to the development of the script and, based on this analysis, identifies opportunities to move the talks forward.
Dynamic Fire Danger Mapping from Satellite Imagery and Meteorological Forecast Data
Authors: Fiorucci Paolo , Gaetani Francesco , Lanorte Antonio , Lasaponara Rosa 
Published: July 2007

Abstract
This study aims at ascertaining if and how remote sensing data can improve fire danger estimation based on meteorological variables. With this goal in mind, a dynamic estimation of fire danger was performed using an approach based on the integration of satellite information within a comprehensive fire danger rating system. The performances obtained with and without using satellite data were carried out for fires that occurred during the fire season in the year 2003 in the Calabria region (southern Italy). This study area was selected, first, because it is highly representative of Mediterranean ecosystems and, second, because it is an interesting test case for wildfire occurrences within the Mediterranean basin.
The results obtained have shown that the use of satellite data reduced efficiently the overestimated danger areas, thus improving at least by 10% the fire forecasting rate obtained without using satellite-based maps. Such findings can be directly extended to other similar Mediterranean ecosystems.
Thalidomide induces γ-globin gene expression through increased reactive oxygen species–mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis
Authors: Aerbajinai Wulin , Zhu Jianqiong , Gao Zhigang , Chin Kyung , Rodgers Griffin P. 
Published: July 2007

Abstract
Although thalidomide has been shown to improve anemia in some patients with myelodysplastic syndromes and stimulates erythropoietin in patients with multiple myeloma, thalidomide's specific effects on γ-globin gene expression during erythroid differentiation have not been studied. Here, we investigated the effects of thalidomide on γ-globin gene expression and the involved signaling pathway using an ex vivo culture system of primary human CD34+ cells. We found that thalidomide induced γ-globin mRNA expression in a dose-dependent manner, but had no effect on β-globin expression. We also demonstrated that intracellular reactive oxygen species (ROS) levels were increased by treatment with thalidomide for 48 hours (from day 3 to day 5). Western blot analysis demonstrated that thalidomide activated the p38 mitogen-activated protein kinase (MAPK) signaling pathway in a time- and dose-dependent manner and increased histone H4 acetylation. Pretreatment of cells with the antioxidant enzyme catalase and the intracellular hydroxyl scavenger dimethylthiourea (DMTU) abrogated the thalidomide-induced p38 MAPK activation and histone H4 acetylation. Moreover, pretreatment with catalase and DMTU diminished thalidomide-induced γ-globin gene expression. These data indicate that thalidomide induces increased expression of the γ-globin gene via ROS-dependent activation of the p38 MAPK signaling pathway and histone H4 acetylation.