bluuebunny/crossref_metadata_2025_split huggingface dataset:
New drug targets for pulmonary hypertension: Rho GTPases in pulmonary vascular remodelling
Authors: Wojciak-Stothard B 
Published: August 2008

AbstractRho GTPases, key regulators of actin dynamics, play a major role in vascular processes such as endothelial permeability, cell motility, angiogenesis, nitric oxide production, smooth muscle contractility, cell proliferation and differentiation. In the lung, Rho GTPases control pulmonary vascular tone and remodelling. Their basal activity is important in fetal lung development and vascular adaptation to changes in oxygen levels, but their continuous activation in neonatal or adult lung leads to the development of pulmonary hypertension (PH), a condition characterised by excessive remodelling and hyperconstriction of pulmonary arteries. This review, based on recent molecular, cellular and animal studies, focuses on the current understanding of Rho GTPases signalling in pulmonary vascular physiology and pathophysiology. It also discusses the existing and prospective treatments targeting Rho GTPases in the management of PH.
Lung cancer mimicking left atrial mass
Authors: Kadappu K K , Rajaratnam R , Kachwalla H , Nguyen P D 
Published: August 2008

Abstract
Cardiac involvement in lung cancer is found in up to 25% of autopsy cases. However, despite the considerable mortality and morbidity associated with cardiac metastasis, antemortem diagnosis is unusual. A rare case of lung cancer presenting as a left atrial mass is reported.
See one, do one, then what? Faculty development in postgraduate medical education
Authors: Swanwick T 
Published: August 2008

Abstract
Interest in the development of medical educators working in the postgraduate sector is running high. Driven by three interlinked trends—the professionalisation of medical education, increasing accountability, and the pursuit of educational excellence—there is a growing need for high quality and sustained faculty development programmes across the network of education providers. Postgraduate medical education has a number of unique features that set it apart from undergraduate medicine, to which faculty development programmes need to cater. The key issue for the future will be how to engage the service in the business of education. Widespread cultural change is required and this will require effective and sympathetic leadership from postgraduate training institutions, hospitals and health authorities.
What Does Teaching Do to Teachers?
Authors: McArthur John T. 
Published: August 2008

Studies of people-processing organizations invariably concentrate on the clients of such organizations. It is equally interesting to consider the staff of these organizations. Does working in such an organization re shape the ideologies and attitudes of the staff? Should we pay more at tention to the process of socialization of "those who socialize"? This ar ticle reports a longitudinal study that monitored a group of Australian secondary teachers from their final year of training into their initial year of teaching. It replicates previous studies in North America and England that employed the Pupil Control Ideology Form and other measures of teachers' attitudes toward pupils to examine the phenomenon of begin ning teacher socialization. The results of the study confirm in an Austra lian context the general thrust of earlier studies: that beginning teachers experience an ideological shift from idealism to realism during their ini tial teaching experience. John T. McArthur is Head of Area of Educational Administration, Monash University, Clayton, Victoria, Australia.
Clinical and financial analysis of an acute palliative care unit in an oncological department
Authors: Mercadante S , Intravaia G , Villari P , Ferrera P , David F , Casuccio A , Mangione S 
Published: August 2008

The aim of this article is to describe the clinical activity and medical intervention of an acute model of palliative care unit (APC), as well as the reimbursement procedures and economic viability. A sample of 504 patients admitted at an APC in 1 year was surveyed. Indications for admission, pain and symptom intensity, analgesic treatments, procedures, instrumental examinations and modalities of discharge were recorded. For each patient, tariff for reimbursement was calculated according to the existent disease related grouping (DRG) system. The mean age was 62 years, and 246 patients were males. The mean hospital stay was 5.4 days. Pain control was the most frequent indication for admission. All patients had laboratory tests and several instrumental examinations. Almost all patients were prescribed one or more opioids at significant doses, and different routes of administration, as well as medication as needed. 59 patients received blood cell transfusions and 34 interventional procedures. Only 40 patients died in the unit, 11 of them being sedated at the end of life. Treatment efficacy was considered optimal and mild in 264 and 226 patients respectively. A mean of 3019 euros for admission was reimbursed by the Health Care System. APCs are of paramount importance within an oncological department, as they provide effective and intensive treatments during the entire course of disease, providing a simultaneous and integrated approach. Our findings also suggest both a cost and quality incentive for oncological departments to develop APC.
CYP2A6 activity in a healthy Spanish population: effect of age, sex, smoking, and oral contraceptives
Authors: Sinues B , Fanlo A , Mayayo E , Carcas C , Vicente J , Arenaz I , Cebollada A 
Published: August 2008

This study was performed to assess the influence of age, sex, smoking, and contraceptive use on CYP2A6 activity. In the metabolism of caffeine, the conversion of 1,7 dimethylxanthine (17X) to 1,7 dimethiylurate (17U) is catalyzed primarily by CYP2A6. CYP2A6 phenotype was determined by the urinary ratio 17U:17X in the interval of 4–5 h after caffeine intake in 179 healthy white Spaniards (102 women and 76 men). There were 99 non-smokers and 80 smokers. Among women, 26 were taking oral contraceptives. The age was the most important predictive factor of CYP2A6 activity ( P < 0.001) with older subjects having higher activity. The influence of the gender was more modest ( P = 0.07) with women exhibiting borderline increased values of the CYP2A6 marker than men. Tobacco smoking did not affect CYP2A6 activity. However, the CYP2A6 marker resulted to be strongly related to the use of oral contraceptives. The women users of oral contraceptives had higher values of CYP2A6 marker than both women not taking oral contraceptives and men ( P < 0.001 in both comparisons). The results indicate that age, oral contraceptive use, and possibly gender should be controlled in epidemiological studies dealing with CYP2A6 activity and its relationship with xenobiotics exposure and genetic or pathological factor.
Melittin-induced [Ca2+]i increases and subsequent death in canine renal tubular cells
Authors: Liu SI , Cheng HH , Huang CJ , Chang HC , Chen WC , Chen IS , Hsu SS , Chang HT , Huang JK , Chen JS , Lu YC , Jan CR 
Published: August 2008

The effect of melittin on cytosolic free Ca2+ concentration ([Ca2+]i) and viability is largely unknown. This study examined whether melittin alters Ca2+ levels and causes Ca2+-dependent cell death in Madin-Darby canine kidney (MDCK) cells. [Ca2+]i and cell death were measured using the fluorescent dyes fura-2 and WST-1 respectively. Melittin at concentrations above 0.5 μM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 75% by removing extracellular Ca2+. The melittin-induced Ca2+ influx was also implicated by melittin-caused Mn2+ influx. After pretreatment with 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), melittin-induced Ca2+ release was inhibited; and conversely, melittin pretreatment abolished thapsigargin-induced Ca2+ release. At concentrations of 0.5–20 μM, melittin killed cells in a concentration-dependent manner. The cytotoxic effect of 0.5 μM melittin was nearly completely reversed by prechelating cytosolic Ca2+ with BAPTA. Melittin at 0.5–2 μM caused apoptosis as assessed by flow cytometry of propidium iodide staining. Collectively, in MDCK cells, melittin induced a [Ca2+]i rise by causing Ca2+ release from endoplasmic reticulum and Ca2+ influx from extracellular space. Furthermore, melittin can cause Ca2+-dependent cytotoxicity in a concentration-dependent manner.
IL-1β as a determinant in silica-induced cytokine responses in monocyte-endothelial cell co-cultures
Authors: Herseth JI , Refsnes M , Låg M , Hetland G , Schwarze PE 
Published: August 2008

Alveolar macrophages and endothelial cells are both involved in lung inflammation and remodeling of lung alveolar structures. In the present study, monocytes (precursors for macrophages) were exposed to crystalline silica and examined for pro- and anti-inflammatory cytokine responses in non-contact co-cultures with endothelial cells. The time courses for silica-induced release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-8 both from co-cultures and monocyte mono-cultures showed an early peak at 5–10 h, almost no response at 20 h, and a strong increase at 43 h. At 43 h, co-cultures also showed strongly increased IL-6 levels. Steady-state levels of mRNA roughly exhibited the same pattern of early up-regulation and reduced levels at 20 h. Compared with monocyte mono-cultures, silica induced a strong release of IL-1β, IL-6, and IL-8, but not of TNF-α, after 43 h in co-cultures, whereas at 5 and 10 h a significant difference was only observed for the silica-induced IL-8 response. An antagonist to the IL-1 receptor strongly reduced IL-6 and IL-8 levels, whereas antibodies to TNF-α increased the levels of IL-1β and IL-8. Thus, IL-1β is suggested to be an important triggering factor that determines the silica-induced release of several of the other cytokines in this co-culture system.
Synergistic action of sodium selenite and N-acetylcysteine in acetaminophen-induced liver damage
Authors: Yalçın SS , Bilgili A , Onbaşılar İ , Eraslan G , Özdemir M 
Published: August 2008

Acetaminophen (AAP) is a commonly used analgesic and antipyretic drug; however, when used in high doses, it causes fulminant hepatic necrosis in both humans and experimental animals. In this study, we investigated whether selenium (Se) and N-acetylcysteine (NAC), alone or in combination, are protective against AAP toxicity in mice. At the beginning of the experiment, blood samples were taken from 10 of 350 mice. Then, the remaining mice were randomly allocated into four groups, each consisting of 35 animals. The 1st group received a single administration of AAP by gavage at a dose of 600 mg/kg-bw, p.o. The 2nd group (AAP-Se) was treated with sodium selenite (0.5 mg Se/kg-bw, p.o.) one hour after ingestion of AAP. The 3rd group (AAP-NAC) ingested AAP, 1.5 h later followed by NAC (500 mg/kg-bw, p.o.). The 4th group (AAP-Se-NAC) was given sodium selenite and NAC, 1 and 1.5 h after administration of AAP, respectively. From each group, blood samples of seven mice for each time point were taken at 4, 8, 24, and 48 h after AAP toxicity. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) levels were measured. Compared with AAP group, the levels of ALT were lower after AAP ingestion in AAP-NAC, AAP-Se, and AAP-Se-NAC groups at the 8th hour. ALT, AST, and LDH levels in AAP-Se-NAC group were 50% of the levels of other groups starting form the 4th hour of toxicity. It is concluded that protection against AAP hepatotoxicity using a combination of Se and NAC is better than that found with either agent alone.
European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor
Authors: Marin David , Milojkovic Dragana , Olavarria Eduardo , Khorashad Jamshid S. , de Lavallade Hugues , Reid Alistair G. , Foroni Letizia , Rezvani Katayoun , Bua Marco , Dazzi Francesco , Pavlu Jiri , Klammer Matthias , Kaeda Jaspal S. , Goldman John M. , Apperley Jane F. 
Published: August 2008

Abstract
The majority of patients with chronic myeloid leukemia in chronic phase gain substantial benefit from imatinib but some fail to respond or lose their initial response. In 2006, the European LeukemiaNet published recommendations designed to help identify patients responding poorly to imatinib. Patients were evaluated at 3, 6, 12, and 18 months and some were classified as “failure” or “suboptimal responders.” We analyzed outcomes for 224 patients with chronic myeloid leukemia in chronic phase treated in a single institution to validate these recommendations. Patients were followed for a median of 46.1 months. At each time point, patients classified as “failure” showed significantly worse survival, progression-free survival, and cytogenetic response than other patients; for example, based on the assessment at 12 months, the 5-year survival was 87.1% versus 95.1% (P = .02), progression-free survival 76.% versus 90% (P = .002), and complete cytogenetic response rate 26.7% versus 94.1% (P < .001). Similarly, the criteria for “suboptimal response” at 6 and 12 months identified patients destined to fare badly, although criteria at 18 months were less useful. The predictive value of some other individual criteria varied. In general, the LeukemiaNet criteria have useful predictive value, but a case could now be made for combining the categories “failure” and “suboptimal response.”
Identification of low penetrance alleles for lung cancer: The GEnetic Lung CAncer Predisposition Study (GELCAPS)
Authors: Eisen Tim , Matakidou Athena , Houlston Richard ,   the GELCAPS Consortium
Published: August 2008

Abstract

Background
Part of the inherited risk to lung cancer is likely to include common, low risk alleles. The identification of this class of susceptibility is contingent on association-based analyses. We established GEnetic Lung CAncer Predisposition Study (GELCAPS) to collect DNA and clinico-pathological data from a large series of cases and a series of spouse/partner controls, thereby generating a key resource for the identification of low risk alleles.

Methods
GELCAPS was one of the first genetic epidemiological trials in the UK to be adopted by the National Cancer Research Network (NCRN) onto its portfolio with the participation of over 100 oncology departments specialising in the management of lung cancer.

Results
Samples from over 5,000 independent lung cancer cases and 2,000 controls have so far been assembled through GELCAPS.

Conclusion
GELCAPS represents one of the largest datasets of its type in the world capable of informing on the contribution of low penetrance alleles to the development of lung cancer and the influence of genetic variation on outcome. In addition our experience in developing the GELCAPS serves to illustrate how large DNA biobanks for genetic analyses can be rapidly generated within the UK using the NCRN.
The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate
Authors: Lopez-Rios Javier , Esteve Pilar , Ruiz Jose Maria , Bovolenta Paola 
Published: August 2008

Abstract
Background
Secreted frizzled related proteins (SFRPs) are multifunctional modulators of Wnt and BMP (Bone Morphogenetic Protein) signalling necessary for the development of most organs and the homeostasis of different adult tissues. SFRPs fold in two independent domains: the cysteine rich domain (SfrpCRD) related to the extracellular portion of Frizzled (Fz, Wnt receptors) and the Netrin module (SfrpNTR) defined by homologies with molecules such as Netrin-1, inhibitors of metalloproteinases and complement proteins. Due to its structural relationship with Fz, it is believed that SfrpCRD interferes with Wnt signalling by binding and sequestering the ligand. In contrast, the functional relevance of the SfrpNTR has been barely addressed.

Results
Here, we combine biochemical studies, mutational analysis and functional assays in cell culture and medaka-fish embryos to show that the Sfrp1NTR mimics the function of the entire molecule, binds to Wnt8 and antagonizes Wnt canonical signalling. This activity requires intact tertiary structure and is shared by the distantly related Netrin-1NTR. In contrast, the Sfrp1CRD cannot mirror the function of the entire molecule in vivo but interacts with Fz receptors and antagonizes Wnt8-mediated β-catenin transcriptional activity.

Conclusion
On the basis of these results, we propose that SFRP modulation of Wnt signalling may involve multiple and differential interactions among Wnt, Fz and SFRPs.
Identification and characterization of infiltrating macrophages in acetaminophen-induced liver injury
Authors: Holt Michael P , Cheng LinLing , Ju Cynthia 
Published: August 2008

AbstractThe role of macrophages in the pathogenesis of acetaminophen (APAP)-induced liver injury remains controversial, as it has been demonstrated that these cells display pro-toxicant and hepato-protective functions. This controversy may stem from the heterogeneity and/or plasticity of macrophages and the difficulty in distinguishing and differentially studying subpopulations of macrophages in the liver. In the present study, using flow cytometric analysis and fluorescence-labeled antibodies against specific cell surface macrophage markers, we were able to, for the first time, identify an APAP-induced macrophage (IM) population distinct from resident Kupffer cells. The data demonstrated that the IMs were derived from circulating monocytes that infiltrated the liver following APAP-induced liver injury. The IMs exhibited a phenotype consistent with that of alternatively activated macrophages and demonstrated the ability to phagocytize apoptotic cells and induce apoptosis of neutrophils. Furthermore, in the absence of the IMs, the resolution of hepatic damage following APAP-induced hepatotoxicity was delayed in CCR2−/− mice compared with wild-type mice. These findings likely contribute to the role of the IMs in the processes of tissue repair, including counteracting inflammation and promoting angiogenesis. The present study also demonstrated the ability of separating populations of macrophages and delineating distinct functions of each group in future studies of inflammatory disease in the liver and other tissues.
Effects of Weight Loss after Bariatric Surgery for Morbid Obesity on Vascular Endothelial Growth Factor-A, Adipocytokines, and Insulin
Authors: García de la Torre Nuria , Rubio Miguel A. , Bordiú Elena , Cabrerizo Lucio , Aparicio Eugenio , Hernández Carmen , Sánchez-Pernaute Andrés , Díez-Valladares Luis , Torres Antonio J. , Puente Montserrat , Charro Aniceto L. 
Published: August 2008

Background: Adipocytes regulate blood vessel formation, and in turn endothelial cells promote preadipocyte differentiation through the expression of proangiogenic factors, such as vascular endothelial growth factor (VEGF)-A. Some adipocytokines and hormones also have an effect on vascular development.Objectives: Our objectives were to analyze the relationship between weight and circulating VEGF-A in morbidly obese subjects before and after bariatric surgery, and investigate the relationship between circulating VEGF-A and certain adipocytokines and hormones regulating adipocytes.Methods: A total of 45 morbidly obese women and nine lean females were included in the study. Patients underwent bariatric surgery: vertical banded gastroplasty (n = 17), gastric bypass (n = 17), and biliopancreatic diversion (n = 11). Serum samples for VEGF-A, adiponectin, leptin, ghrelin, and insulin were obtained preoperatively and 9–12 months after surgery.Results: Obese patients showed significantly higher VEGF-A levels than controls (306.3 ± 170.3 vs. 187.6 ± 91.9 pg/ml; P = 0.04), decreasing to 246.1 ± 160.4 after surgery (P &lt; 0.001), with no differences among surgical procedures. In controls there was an inverse correlation between VEGF-A and ghrelin (r = −0.85; P &lt;.01), but not in obese patients. Leptin and insulin concentrations were increased in obese patients, with a significant decrease shown after weight loss with surgery. Conversely, adiponectin concentrations were lower in obese patients, with a significant increase shown after weight loss with surgery. Ghrelin was higher in controls than obese patients, decreasing after gastric bypass and biliopancreatic diversion, but not after vertical banded gastroplasty.Conclusion: Serum VEGF-A levels are significantly higher in obese patients than in lean controls, decreasing after weight loss with bariatric surgery, behaving similarly to other hormones related to adipose mass like leptin and insulin.
Development of an Adrenocorticotropin-Responsive Human Adrenocortical Carcinoma Cell Line
Authors: Parmar Jeniel , Key Rebecca E. , Rainey William E. 
Published: August 2008

Context: The molecular mechanisms regulating adrenal steroidogenesis continue to be defined. The only current human adrenocortical cell line is the NCI-H295 and its substrains. One of the strains, H295R, has retained the ability to respond to angiotensin II (Ang II); however, it lacks ACTH responsiveness. An ACTH-responsive human adrenocortical model would add significantly to studies directed at defining the molecular control of corticosteroid biosynthesis.
Objective: The objective of the study was to develop a human adrenal cell line that retained both Ang II- and ACTH-regulated corticosteroid production.
Design: Human adrenocortical carcinoma (HAC) cells were isolated from an adrenal tumor removed from a girl presenting with virilization and hypertension. Clonal populations of cells were established and characterized. HAC cells were treated with ACTH, Ang II, and forskolin, followed by examination of steroidogenic enzyme mRNA expression using quantitative real-time PCR and steroid production.
Results: HAC clone 15 (HAC15) cells responded to treatment with ACTH, Ang II, and forskolin, with increased cortisol and aldosterone production. ACTH, Ang II, and forskolin also increased expression of mRNA, encoding all enzymes needed for cortisol and aldosterone biosynthesis, namely steroidogenic acute regulatory protein, cholesterol side-chain cleavage, cytochrome P450 17α-hydroxylase-17, 20-lyase, 3β-hydroxysteroid dehydrogenase type II, 21-hydroxylase, 11β-hydroxylase, and 11β-aldosterone synthase. In addition, the cells expressed mRNA for ACTH receptor (MC2R) and Ang II receptor. MC2R protein was also expressed in HAC15 cells.
Conclusion: The current study describes the development and characterization of an ACTH- and Ang II-responsive human adrenal cell line. The HAC15 cell line should provide an important model system for defining the molecular mechanisms regulating aldosterone and cortisol production.
High-stress three-body abrasive wear of treated and untreated oil palm fibre-reinforced polyester composites
Authors: Yousif B F , El-Tayeb N S M 
Published: August 2008

The aim of this study is to investigate the effect of treated and untreated oil palm fibres on high-stress three-body abrasive wear characteristics of polyester composites. Experimental tests were conducted at different applied loads (5–20 N) and two different rotational speeds (50 and 100 r/min) for 0.18 km sliding distance using a dry sand/steel wheel apparatus. The flow of the sand particles (560–900 μm) was 4.5 g/s. Morphologies of the worn surface of the composites were studied using a scanning electron microscope (SEM). Pull-out test was carried out to evaluate the interfacial adhesion characteristics of treated and untreated fibres. The results revealed that composites based on treated oil palm fibres exhibited better wear performance compared with untreated ones, i.e. the interfacial adhesion of treated fibres to the polyester was better than untreated fibres. Moreover, treated oil palm fibres were found to reduce the porosity of the composite, which in turn stabilized the surface tribo-characteristics. Based on the SEM analysis, the wear mechanisms were predominated by pitting, grooving, microcracking, microcutting, and fracture in the polyester region.