bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simvastatin protects against cholestasis‐induced liver injury
Authors: Dold S , Laschke MW , Lavasani S , Menger MD , Jeppsson B , Thorlacius H 
Published: January 2009

Mandarin translation of abstractBackground:  Bile duct obstruction is associated with hepatic accumulation of leukocytes and liver injury. The aim of this study was to evaluate the effect of simvastatin on cholestasis‐induced liver inflammation and tissue damage.Experimental approach:  C57BL/6 mice were treated with simvastatin (0.02 and 0.2 mg·kg−1) and vehicle before and after undergoing bile duct ligation (BDL) for 12 h. Leukocyte recruitment and microvascular perfusion in the liver were analysed using intravital fluorescence microscopy. CXC chemokines in the liver were determined by enzyme‐linked immunosorbent assay. Liver damage was monitored by measuring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Hepatic levels of myeloperoxidase (MPO) were also determined.Key results:  Administration of 0.2 mg·kg−1 simvastatin decreased ALT and AST by 87% and 83%, respectively, in BDL mice. This dose of simvastatin reduced hepatic formation of CXC chemokines by 37–82% and restored sinusoidal perfusion in cholestatic animals. Moreover, BDL‐induced leukocyte adhesion in sinusoids and postsinusoidal venules, as well as MPO levels in the liver, was significantly reduced by simvastatin. Notably, administration of 0.2 mg·kg−1 simvastatin 2 h after BDL induction also decreased cholestatic liver injury and inflammation.Conclusions and implications:  These findings show that simvastatin protects against BDL‐induced liver injury. The hepatoprotective effect of simvastatin is mediated, at least in part, by reduced formation of CXC chemokines and leukocyte recruitment. Thus, our novel data suggest that the use of statins may be an effective strategy to protect against the hepatic injury associated with obstructive jaundice. Mandarin translation of abstract
Division Manager Lobbying Power and the Allocation of Capital
Authors: McNeil Chris R. , Smythe Thomas I. 
Published: January 2009

AbstractWe investigate whether division manager lobbying power affects the allocation of capital in multi‐divisional firms. We find that firm‐level disparities in division manager lobbying power (measured by tenure, time‐in‐position, board membership, and top executive status) affect capital allocation in expected ways. Managers with greater relative lobbying power compete for capital expenditures from a position of strength. Evidence is also provided which suggests that division manager ownership mitigates lobbying efforts. Furthermore, disparity in division manager lobbying power is associated with lower firm excess value. These results support the view that division manager influence activities impact the operation of internal capital markets.
The Diversification Discount Puzzle: Evidence for a Transaction‐Cost Resolution
Authors: Aggarwal Raj , Zhao Shelly 
Published: January 2009

AbstractThe literature on the corporate diversification discount and the relative efficiency of internal versus external capital markets provides mixed results. We argue that transaction‐cost economics is useful in understanding this puzzle. According to transaction‐cost economics, diversified firms should outperform single segment firms in industries with higher external transaction costs (e.g., emergent industries) and under‐perform in industries with low external transaction costs and high agency and other internal costs (e.g., some mature industries). This paper provides evidence supporting these contentions.
Anti‐inflammatory effects of low molecular weight heparin derivative in a rat model of carrageenan‐induced pleurisy
Authors: Ceccarelli Matteo , Bani Daniele , Cinci Lorenzo , Nistri Silvia , Uliva Caterina , Ragazzo Elena , Vannacci Alfredo , Manoni Marco , Gori Anna Maria , Abbate Rosanna , Gensini Gian Franco , Masini Emanuela 
Published: January 2009

SummaryLow molecular weight heparin derivatives are characterized by low anti‐coagulant activity and marked anti‐inflammatory effects that allow for these molecules to be viewed as a new class of non‐steroidal anti‐inflammatory drugs (NSAIDs). We show here that K5NOSepiLMW, an O‐sulphated heparin‐like semi‐synthetic polymer of the D‐glucuronic acid–N‐acetyleparoson disaccharide unit with low molecular weight, has marked anti‐inflammatory effects in a rat model of acute inflammation, the carrageenan‐induced pleurisy, commonly used to test NSAID efficacy. A 30‐min. pre‐treatment with K5NOSepiLMW (0.1, 0.5 and 1 mg/kg b.wt., given intrapleurally) attenuated the recruitment of leucocytes in the lung tissue and the pleural exudate, inhibited the induction of inducible nitric oxide synthase and cyclooxygenase‐2 (COX‐2), thereby abating the generation of nitric oxide and pro‐inflammatory prostaglandins such as PgE2 and PGF1α, reduced the inflammation‐induced nitroxidative lung tissue injury, as shown by tissue thiobarbituric acid‐reactive substances and nitrotyrosine, and blunted the local generation of cytokines such as interleukin‐1β and tumour necrosis factor‐α. All these parameters were markedly increased by intrapleural carrageenan in the absence of any pre‐treatment. The anti‐inflammatory action of K5NOSepiLMW is specific, as judged by the lack of therapeutic effects of B4/110, a biologically inactive cognate polysaccharide, given in the place of the authentic molecule. Moreover, K5NOSepiLMW showed similar effects as celecoxib (1 mg/kg b.wt), a COX‐2 inhibitor and well‐known NSAID. This study provides further insight into the mechanisms underlying the beneficial effects of heparin derivatives in inflammation and identifies K5NOSepiLMW as a novel, promising anti‐inflammatory drug.
Prospective analysis of the incidence of autoimmune bullous disorders in Lower Franconia, Germany
Authors: Bertram Franziska , Bröcker Eva‐B. , Zillikens Detlef , Schmidt Enno 
Published: January 2009

Summary Background: Only limited epidemiologic data are available on autoimmune bullous diseases. Improved diagnostic tools should have led to an increased incidence. To test this hypothesis, all patients with autoimmune bullous disorders who were treated in the Department of Dermatology at the University of Würzburg, Germany, between January 2001 and June 2002 were analysed prospectively. Patients and Methods: Epidemiologic data of patients diagnosed with an autoimmune bullous disease during this time period were registered and statistically evaluated. Diagnosis was based on the clinical picture and specific immunopathological findings. Only patients from Lower Franconia, a well‐defined administrative region of Southern Germany, were included into this study. Results: During the study period, 41 patients with an autoimmune bullous disease were diagnosed, including 27 with bullous pemphigoid, 4 with pemphigoid gestationis and mucous membrane pemphigoid, 2 with dermatitis herpetiformis and linear IgA disease, and 1 with epidermolysis bullosa acquisita and pemphigus vulgaris, respectively. The highest incidence was calculated for bullous pemphigoid (13.4 per 1 million inhabitants per year) followed by pemphigoid gestationis (2.0) and mucous membrane pemphigoid (2.0). Patients with mucous membrane pemphigoid were found to have the highest mean age at disease onset (76 years) followed by patients with bullous pemphigoid (74 years). Conclusions: This is the first prospective study on the incidence of autoimmune bullous disorders. Subepidermal blistering autoimmune diseases were shown to be more frequent than previously reported for Central Europe. This is most likely due to improved diagnostic tools for and increased awareness of these diseases.
Skin diseases and sexually transmitted diseases in HIV‐infected patients on HAART compared to a non‐infected population – results of a retrospective study
Authors: Rothengatter Sonja , Sehr Tanja , Gholam Patrick , Durani Hendrike , Hartmann Martin 
Published: January 2009

Summary Background: The prevalence of skin diseases and sexually transmitted diseases has always played a special role in studying HIV infections, both because of immunosuppression and simultaneous transmission. In the early years of the HIV epidemic, skin diseases were often a pathognomonic sign in heavily immunosuppressed patients. With highly active antiretroviral therapy (HAART), HIV infection has become a treatable chronic disease. For this reason the spectrum as well as the prevalence of skin diseases has changed. Pathognomonic skin diseases have become rare and the wide spectrum today ranges from infectious to iatrogenic skin diseases. Patients and methods: From April to October 2007 166 HIV‐infected patients and 173 patients of a comparison group were surveyed in retrospect by means of a questionnaire about skin diseases and sexually transmitted diseases that appeared over the entire year 2006. Results and conclusions: The study confirmed the shift to a wide variety of mostly trivial skin diseases and away from severe opportunistic skin diseases. HIV‐infected patients today have more numerous skin problems than the non‐infected population and thus need regular dermatologic control examinations.
Pulse oximetry screening as a complementary strategy to detect critical congenital heart defects
Authors: Meberg Alf , Andreassen Andreas , Brunvand Leif , Markestad Trond , Moster Dag , Nietsch Lutz , Silberg Inger Elisabeth , Skålevik Jan Einar 
Published: January 2009

AbstractObjective: To compare strategies with and without first‐day of life pulse oximetry screening to detect critical congenital heart defects (CCHDs).Study design: Population based study including all live born infants in Norway in 2005 and 2006 (n = 116 057). Postductal (foot) arterial oxygen saturation (SpO2) was measured in apparently healthy newborns after transferral to the nursery, with SpO2 < 95% as cut‐off point. Out of 57 959 live births in the hospitals performing pulse oximetry screening, 50 008 (86%) were screened.Results: A total of 136 CCHDs (1.2 per 1000) were diagnosed, 38 (28%) of these prenatally. Of the CCHDs detected after birth, 44/50 (88%) were detected before discharge in the population offered pulse oximetry screening (25 by pulse oximetry), compared to 37/48 (77%) in the non‐screened population (p = 0.15). Median times for diagnosing CCHDs in‐hospital before discharge were 6 and 16 h after birth respectively (p < 0.0001). In the screened population 6/50 (12%) CCHDs were missed and recognized after discharge because of symptoms. Two of the six missed cases failed the pulse oximetry screening, but were overlooked (echocardiography not performed before discharge). If these cases had been recognized, 4/50 (8%) would have been missed compared to 11/48 (23%) in the non‐screened population (p = 0.05). Of the cases missed, 14/17 (82%) had left‐sided obstructive lesions.Conclusion: First‐day of life pulse oximetry screening provides early in‐hospital detection of CCHDs and may reduce the number missed and diagnosed after discharge.
Early working memory and maternal communication in toddlers born very low birth weight
Authors: Lowe Jean , Erickson Sarah J , MacLean Peggy , Duvall Susanne W 
Published: January 2009

AbstractAim: Early working memory is emerging as an important indicator of developmental outcome predicting later cognitive, behavioural and academic competencies. The current study compared early working memory in a sample of toddlers (18–22 months) born very low birth weight (VLBW; n = 40) and full term (n = 51) and the relationship between early working memory, mental developmental index (MDI), and maternal communication in both samples.Methods: Early working memory, measured by object permanence; Bayley mental developmental index; and maternal communication, coded during mother‐toddler play interaction, were examined in 39 toddlers born VLBW and 41 toddlers born full term.Results: Toddlers born VLBW were found to be 6.4 times less likely to demonstrate attainment of object permanence than were toddlers born full term, adjusting for age at testing. MDI and maternal communication were found to be positively associated with attainment of object permanence in the VLBW group only.Conclusion: The difference found in the early working memory performance of toddlers born VLBW, compared with those born full term, emphasizes the importance of assessing early working memory in at‐risk populations, while the maternal communication finding highlights potential targets of intervention for improving working memory in toddlers born VLBW.
Modified C‐Reactive Protein Is Expressed by Stroke Neovessels and Is a Potent Activator of Angiogenesis In Vitro
Authors: Slevin Mark , Matou‐Nasri Sabine , Turu Marta , Luque Ana , Rovira Norma , Badimon Lina , Boluda Susana , Potempa Lawrence , Sanfeliu Coral , De Vera Nuria , Krupinski Jerzy 
Published: January 2009

AbstractNative C‐reactive protein (nCRP) is a pentameric oligo‐protein and an acute phase reactant whose serum expression is increased in patients with inflammatory disease. We have identified by immunohistochemistry, significant expression of a tissue‐binding insoluble modified version or monomeric form of CRP (mCRP) associated with angiogenic microvessels in peri‐infarcted regions of patients studied with acute ischaemic stroke. mCRP, but not nCRP was expressed in the cytoplasm and nucleus of damaged neurons. mCRP co‐localized with CD105, a marker of angiogenesis in regions of revascularisation. In vitro investigations demonstrated that mCRP was preferentially expressed in human brain microvessel endothelial cells following oxygen‐glucose deprivation and mCRP (but not column purified nCRP) associated with the endothelial cell surface, and was angiogenic to vascular endothelial cells, stimulating migration and tube formation in matrigel more strongly than fibroblast growth factor‐2. The mechanism of signal transduction was not through the CD16 receptor. Western blotting showed that mCRP stimulated phosphorylation of the key down‐stream mitogenic signalling protein ERK1/2. Pharmacological inhibition of ERK1/2 phosphorylation blocked the angiogenic effects of mCRP. We propose that mCRP may contribute to the neovascularization process and because of its abundant presence, be important in modulating angiogenesis in both acute stroke and later during neuro‐recovery.
Leveling the Playing Field: Negotiating Opportunities and Recognition in Gendered Jobs
Authors: Roth Louise Marie 
Published: January 2009

AbstractIn gendered jobs, how do women and men negotiate opportunities to perform and receive recognition for their accomplishments? Women face disadvantages negotiating the workplace, especially in male‐dominated positions, while men receive advantages even in female‐dominated jobs. This article uses research on gender inequality on Wall Street to illustrate how gender schemas sustain gender inequality in career opportunities, access to networks and mentors, and evaluations of performance. Women on Wall Street faced exclusionary networks and assumptions that men were more competent at finance. The article then focuses on strategies that some women on Wall Street have used to successfully negotiate career opportunities and recognition. These strategies include developing expertise, specializing in financial products, and seeking positions with objective performance criteria.
Negotiating Workplace Equality: A Systemic Approach
Authors: Sturm Susan 
Published: January 2009

AbstractNegotiations can operate as powerful engines of inequality, often because of the institutional and social context placing women and people of color at a systemic disadvantage. Yet, negotiation literature and practice has paid little attention to the question of how to reshape the context within which negotiations proceed. This article provides an approach for connecting individual level negotiations with institutional interventions that reshape the context for those negotiations, so that women and people of color can fully and fairly participate in the interactions and decisions so crucial to their advancement. It first lays out the systemic underpinnings of negotiated inequality, identifying structural disparities in information, networks, cognitive frames, and ground rules. It then identifies the role of organizational catalysts in reshaping the contours within which negotiations occur, and learning from the successes and failures of negotiations aggregated over time and place. Finally, it identifies a set of strategies for tackling the systemic underpinnings of inequality in the negotiation process, including (1) critical reframing through root cause analysis, (2) generating and mobilizing information, (3) developing social capital needed for effective negotiation, (4) creating and connecting opportunity networks, and (5) developing constituencies of accountability.
Role of RFLP using TspRI for carrier detection in Glanzmann’s thrombasthenia: a report on two families
Authors: KANNAN M. , YADAV B. K. , AHMAD F. , SAXENA R. 
Published: January 2009

SummaryGlanzmann’s thrombasthenia (GT) was diagnosed in two patients who presented with bleeding manifestations accompanied by absent platelet aggregation, secondary to adenosine‐5'‐diphosphate, adrenaline, arachidonic acid and collagen. Flow cytometry analysis for GPIIb/IIIa expression was done using CD61 and CD41 markers in these patients and their family members including siblings. The patients were sub typed as Type I as he had absent glycoproteins (GP) IIb/IIIa. Family studies by flow cytometry showed reduced GPII/IIIa expression in both the parents and one sibling. However, western blot showed abnormal GPIIb protein in all the family members including siblings. It is possible that abnormal GPIIb protein by western blot in family members may reflect their carrier status. Patients’ DNA was analyzed for mutation in both the GPIIb and GPIIIa genes by conformational sensitive gel electrophoresis (CSGE), followed by sequencing. CSGE showed defect in exon 12 and the promoter region of GPIIb. By sequence, it was confirmed that both the mutations were homozygous one was c.1028T>C and the other one was M33320.1:g.951G>A. For one of these mutations, restriction fragment length polymorphism (RFLP) was developed to look for the same mutation in all the family members. RFLP was developed using a restriction enzyme (TspRI) against the patient’s mutation, c.1028T>C in exon 12 of GPIIb gene. RFLP followed by gel electrophoresis revealed that the mutation was heterozygous in all the family members. The findings by RFLP were double confirmed by direct DNA sequencing of the exon 12 in all the family members. Thus, TspRI marker may be used as a RFLP marker to predict the carriers in GT families, if the patients’ mutation status is identified.
In vitro studies with ‘acatalasemic‐like’ erythrocytes and hydrogen peroxide: attention to the formation of lysis resistant erythrocytes
Authors: NASCIMENTO H. , BELO L. , FERNANDES J. , ROCHA S. , QUINTANILHA A. , SANTOS‐SILVA A. 
Published: January 2009

SummaryHemolysis assays, using hydrogen peroxide as an oxidant injury agent and sodium azide as a catalase inhibitor, were performed to evaluate how assay conditions affect the development of lysis resistant erythrocytes. The concentration of hydrogen peroxide should be carefully selected for use in hemolysis assays, as it was found to affect the number of water resistant erythrocytes.
The utility of immature reticulocyte fraction as an indicator of erythropoietic response to altitude training in elite cyclists
Authors: NADARAJAN V. S. , OOI C. H. , STHANESHWAR P. , THOMPSON M. W. 
Published: January 2009

SummaryAltitude training is sometimes employed by elite endurance athletes to improve their sea level performance. This improvement results from the increased red cell mass consequent upon the boost in erythropoietin (EPO) level that occurs as a response to the relatively hypoxic environment at high altitudes. We measured serum EPO levels together with various red cell and reticulocyte parameters including immature reticulocyte fraction (IRF) in eight national track‐endurance cyclists, resident at sea‐level, prior to and upon return from an altitude of approximately 1905 m. Reticulocytes and soluble transferrin receptor (sTfR) were significantly increased with reduction in ferritin levels immediately on return from high altitude indicating increased erythropoietic activity. IRF in particular showed a significant peak immediately on return but decline to sub‐baseline levels by day 9, and recovery to baseline by day 16. Our results indicate that IRF is a sensitive marker of erythropoietic status in athletes undergoing altitude training and subsequent loss of EPO stimuli on return to sea level.
CTLA4 and generalized vitiligo: two genetic association studies and a meta‐analysis of published data
Authors: Birlea Stanca A. , LaBerge Greggory S. , Procopciuc Lucia M. , Fain Pamela R. , Spritz Richard A. 
Published: January 2009

SummarySeveral lines of evidence have implicated the gene encoding cytotoxic T lymphocyte antigen 4 (CTLA4) in susceptibility to various autoimmune diseases. However, published studies of genetic association between CTLA4 polymorphisms and vitiligo have yielded conflicting results. Here, we describe two new genetic association studies of CTLA4 single‐nucleotide polymorphisms (SNPs) and generalized vitiligo in two independent Romanian Caucasian (CEU) case‐control cohorts. The first study, of SNPs rs1863800, rs231806, rs231775, rs3087243, rs11571302, rs11571297, and rs10932037, showed no allelic, genotypic, or haplotypic association with generalized vitiligo. The second study, of SNP rs231775, likewise showed no significant association. To enhance statistical power over that of any individual study, we carried out a meta‐analysis that incorporated these two new studies and all other published genetic association studies of CTLA4 SNPs and vitiligo in CEU populations. While there was no association with vitiligo overall, the meta‐analysis showed significant association of SNP rs231775 in that subgroup of vitiligo patients who also had other concomitant autoimmune diseases. Similarly, there was near‐significant association in this same patient subgroup with several other CTLA4 SNPs that are in linkage disequilibrium with rs231775. Our results indicate that the association of CTLA4 with vitiligo is weak, and indeed may be secondary, driven by primary genetic association of CTLA4 with other autoimmune diseases that are epidemiologically associated with vitiligo.
BI‐69A11‐mediated inhibition of AKT leads to effective regression of xenograft melanoma
Authors: Gaitonde Supriya , De Surya K , Tcherpakov Marianna , Dewing Antimone , Yuan Hongbin , Riel‐Mehan Megan , Krajewski Stan , Robertson Gavin , Pellecchia Maurizio , Ronai Ze’ev 
Published: January 2009

SummaryThe AKT/PKB pathway plays a central role in tumor development and progression and is often up‐regulated in different tumor types, including melanomas. We have recently reported on the in silico approach to identify putative inhibitors for AKT/PKB. Of the reported hits, we selected BI‐69A11, a compound which was shown to inhibit AKT activity in in vitro kinase assays. Analysis of BI‐69A11 was performed in melanoma cells, a tumor type that commonly exhibits up‐regulation of AKT. Treatment of the UACC903 human melanoma cells, harboring the PTEN mutation, with BI‐69A11 caused efficient inhibition of AKT S473 phosphorylation with concomitant inhibition of AKT phosphorylation of PRAS40. Treatment of melanoma cells with BI‐69A11 also reduced AKT protein expression, which coincided with inhibition of AKT association with HSP‐90. BI‐69A11 treatment not only caused cell death of melanoma, but also prostate tumor cell lines. Notably, the effect of BI‐69A11 on cell death was more pronounced in cells that express an active form of AKT. Significantly, intra‐peritoneal injection of BI‐69A11 caused effective regression of melanoma tumor xenografts, which coincided with elevated levels of cell death. These findings identify BI‐69A11 as a potent inhibitor of AKT that is capable of eliciting effective regression of xenograft melanoma tumors.