bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Role of Androgens in Mitochondrial Fission and Apoptosis
Authors: Choudhary Vivek , Kaddour-Djebbar Ismail , Lakshmikanthan Vijayabaskar , Ghazaly Taghreed , Thangjam Gagan Singh , Sreekumar Arun , Lewis Ronald W. , Mills Ian G. , Bollag Wendy B. , Kumar M. Vijay 
Published: July 2011

Abstract
Androgen and androgen receptors (AR) play critical roles in the proliferation of prostate cancer through transcriptional regulation of target genes. Here, we found that androgens upregulated the expression of dynamin-related protein 1 (Drp1), which is involved in the induction of mitochondrial fission, a common event in mitosis and apoptosis. Clinical tissue samples and various prostate cancer cell lines revealed a positive correlation between Drp1 and AR levels. Treatment of androgen-sensitive cells with an AR agonist, R1881, and antagonist, bicalutamide, showed that Drp1 is transcriptionally regulated by androgens, as confirmed by an AR ChIP-seq assay. Live imaging experiments using pAcGFP1-Mito stably transfected LNCaP (mito-green) cells revealed that androgen did not induce significant mitochondrial fission by itself, although Drp1 was upregulated. However, when treated with CGP37157 (CGP), an inhibitor of mitochondrial Ca2+ efflux, these cells exhibited mitochondrial fission, which was further enhanced by pretreatment with R1881, suggesting that androgen-induced Drp1 expression facilitated CGP-induced mitochondrial fission. This enhanced mitochondrial fission was correlated with increased apoptosis. Transfection with dominant-negative (DN-Drp1, K38A) rescued cells from increased apoptosis, confirming the role of androgen-induced Drp1 in the observed apoptosis with combination treatment. Furthermore, we found that CGP reduced the expression of Mfn1, a protein that promotes mitochondrial fusion, a process which opposes fission. We suggest that androgen-increased Drp1 enhanced mitochondrial fission leading to apoptosis. The present study shows a novel role for androgens in the regulation of mitochondrial morphology that could potentially be utilized in prostate cancer therapy. Mol Cancer Res; 9(8); 1067–77. ©2011 AACR.
The pharmacokinetic diversity of two von Willebrand factor (VWF)/ factor VIII (FVIII) concentrates in subjects with congenital von Willebrand disease
Authors: Kessler Craig M. , Ken Friedman , Schwartz Bruce A. , Gill Joan C. , Powell Jerry S. ,   for the Wilate® PK Study Investigators
Published: July 2011

SummaryThe pharmacokinetic (PK) profiles of von Willebrand factor (VWF) /factor VIII (FVIII) concentrates are important for treatment efficacy and safety of von Willebrand disease (VWD) patients. This prospective, head-to-head, randomised crossover study compared the PK profile of a new, high purity, human plasma-derived (pd)VWF/FVIII concentrate, Wilate®, with the PK profile of an intermediate purity (pd)VWF/FVIII concentrate, Humate-P¯, in VWD patients. Subjects with inherited VWD were randomised to a single intravenous dose (40 IU/kg VWF ristocetin cofactor activity [VWF:RCo]) of Wilate® or Humate-P¯ in Period 1, and switched to the other study drug in Period 2. Each period was preceded by a washout time of ≥7 days. Coagulation factor parameters were analysed at multiple time-points. Of 22 randomised subjects, 20 had evaluable PK profiles, which indicated comparability for VWF antigen and VWF:RCo between Wilate® and Humate-P¯. The reported VWF:RCo average and terminal t1/2 of 10.4 and 15.8 hours (h), respectively, for Wilate® and 9.3 h and 12.8 h for Humate-P®, were not statistically different. Also, the mean VWF:RCo in vivo recoveries (Wilate® 1.89, Humate-P® 1.99 IU/dl per IU/kg) were similar between the two replacement therapies. Wilate® showed parallel decay curves for VWF:RCo and FVIII clotting activity (FVIII:C) over time, while FVIII:C of Humate-P® displayed a plateau between 0 and 12–24 h. This study demonstrated bioequivalent PK properties for VWF between Wilate® and Humate-P®. The PK profile of Wilate®, combined with the 1:1 VWF/FVIII ratio, theoretically should facilitate dosing and laboratory monitoring of VWF replacement to prevent bleeding in individuals with VWD.
Seasonal and monthly variability in the incidence of venous thromboembolism
Authors: Ageno Walter , Rancan Elena , Donati Alberto , Galli Luca , Squizzato Alessandro , Venco Achille , Mannucci Pier , Manfredini Roberto , Dentali Francesco 
Published: July 2011

SummaryMany studies showed that the occurrence of cardiovascular and cerebrovascular events exhibits a seasonal and monthly variation. Evidences of a seasonal and monthly variation in the incidence of venous thromboembolism (VTE) are more conflicting. We conducted a systematic review and a meta-analysis of the literature to assess the presence of an infradian rhythm of this disease. MEDLINE and EMBASE databases were searched up to January 2010. Monthly and seasonal variation in the incidence of VTE were analysed. We included studies analysing seasonal or monthly aggregation in the incidence of deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) with an objective diagnosis of VTE. Two authors independently reviewed and extracted data. Seventeen studies for a total of about 35,000 patients were included. Twelve studies analysed the seasonal variation and 10 studies the monthly variation of VTE. Our results showed a significantly increased incidence of VTE in winter (chi-square 146.04, p <0.001), with a relative risk (RR) of VTE of 1.143 (99% CI [1.141, 1.144]), and a significantly increased incidence of VTE in January (chi-square 232.57, p <0.001) with an RR of VTE of 1.194 (99% CI 1.186, 1.203). Subgroup analyses including only idiopathic venous thromboembolic events confirmed the results of principal analyses. In conclusion, our data support the presence of an infradian pattern in the incidence of venous thromboembolic events, with a significantly higher risk in Winter and in January. Future studies are needed to better clarify the mechanisms behind this pattern.
Platelet reactivity is a stable and global phenomenon in aspirin-treated cardiovascular patients
Authors: Zufferey Anne , Reny Jean-Luc , Combescure Christophe , Moerloose Philippe de , Sanchez Jean-Charles , Fontana Pierre 
Published: July 2011

SummaryIn healthy subjects, platelet hyperreactivity is a global phenomenon – as opposed to agonist-specific – and epinephrine-induced platelet aggregation (EPA) is a reliable marker of this phenotype. Few data are available on platelet reactivity and the relationship between EPA and aggregation induced by other agonists in cardiovascular patients. It was the objective of this study to characterise platelet reactivity in stable cardiovascular patients treated with aspirin and to derive a composite index integrating several aggregation pathways, suitable for selecting patients with extreme phenotypes for further proteomics analysis. Platelet reactivity to agonists was assessed in 110 patients twice, two weeks apart. Factorial analysis was used to determine whether the results obtained with the different agonists could be summarised in a single composite index. EPA correlated with the aggregation values obtained with each of the other agonists, with correlation coefficients of 0.44 to 0.55 (p<0.001). We constructed a composite “platelet reactivity” index that included 60% of the information provided by each agonist. The results obtained at the first patient visit were consistent with those obtained at the second visit (r=0.78, p<0.01). No clinical or biological parameters correlated with the composite index. The extreme phenotypes of six selected subjects were confirmed 12 months after the second visit. In conclusion, platelet reactivity in aspirin-treated cardiovascular patients is a global phenomenon that can be summarised by a composite index based on the aggregation responses to various agonists and integrating several activation pathways. This index is not dependent on clinical or biological variables, suggesting that genetic factors regulate platelet reactivity in these patients.
The Rebellion in Phanagoria in 63 BC (New Numismatic Evidence)
Authors: Kuznetsov Vladimir D. , Abramzon Mikhail G. 
Published: July 2011

AbstractThe authors publish the coins found in excavations at Phanagoria in 2007-2008, conducted by the Taman Archeological Mission of the Institute of Archaeology, Russian Academy of Sciences. This unique numismatic material allows the authors to clarify a number of important events in the history of the Bosporan Kingdom under Mithradates VI Eupator. The most significant finds of the two archaeological seasons are a so-called “hoard” and two purses containing Bosporan and Pontic coins, many isolated silver coins of Panticapaion and Phanagoria, a tetradrachm of Mithradates VI and a golden piece of jewellery found in a large burnt building situated on the acropolis. These finds are thought to be connected not just with the general historical context of the epoch but specifically with the events of 63 BC.
Tanais and Phanagoria
Authors: Kutinova Tatiana M. 
Published: July 2011

AbstractIn the literature devoted to Tanais the opinion had long held sway to the effect that Tanais maintained special relations with Phanagoria, ever since the idea was first formulated by D. B. Shelov as far back as the beginning of the 1970s. On the basis of an analysis of the collections of stamps found in Tanais and Phanagoria, the scholar concluded that the thrust of the economy and politics of the cities in the Asiatic and European Bosporus must have been different and that the trading activities of Tanais must have been linked first and foremost with Phanagoria. Yet at present, thanks to the accumulation of new material and its reinterpretation, these conclusions can no longer be regarded as well-founded. It would seem that a “common economic space” existed within the confines of the Bosporan state during the Hellenistic period.
Honor in the Early Modern Eastern Mediterranean—an Introduction
Authors: Taylor Scott 
Published: July 2011

AbstractIn the last decade, historians have paid renewed attention to the idea of honor in early modern Europe and elsewhere, but until now, the focus has been primarily on individuals. However, this issue seeks to explore the idea of institutional honor and the question of whether a government could possess a sense of honor and what that would mean for its workings and its impact on its subjects. The themes that emerge in these essays are abduction and sexual misbehavior—where honor and sexual crime could be touchstones for the legitimacy of power. If everyone felt honored, then the hierarchical distribution of power could seem fair; but if the subjects of empire felt humiliated, the power that acted on them would become illegitimate. All of these articles see honor, not as a structure, but as a resource that both state and subject could invoke in a crisis.
The Sexual Politics of Empire: Civic Honor and Official Crime outside Renaissance Venice
Authors: O’Connell Monique 
Published: July 2011

AbstractThis article examines a series of cases in which the Venetian state prosecuted officials who had committed “crimes against honor” during their terms in office. These crimes were mostly sexual in nature, and they thus provide a window into the way that the Venetian state perceived individual and collective honor of state, subject, and officeholder. A key part of the self-definition and thus the reputation of the Venetian state was its ability to ensure peace and defend order. Sex crimes by officials representing the Venetian state did not just violate subjects’ honor; they implicated the Venetian state as a whole in “lawless and tyrannical” actions and undermined Venetian attempts to legitimate its republican empire. The prosecutions of these officials also reveal the sometimes blurry boundaries between public service and private interests in the Venetian state’s administration of its empire.
Goal-Directed Reaching: The SNARC Effect Influences Movement Planning but not Movement Execution
Authors: Bingley Taryn , Heath Matthew 
Published: July 2011

AbstractThe spatial–numerical association of response codes (SNARC effect) is a well-documented phenomenon wherein numerical digits spatially bias the selection of a response, with low and high numbers eliciting faster left and right responses, respectively. A host of button press tasks report expression of the SNARC effect for response planning (i.e., reaction time: RT); however, Fischer (2003) reports that the effect can selectively manifest during the movement execution phase (i.e., movement time: MT) of a goal-directed reaching task. Here we employed a kinematic technique to determine whether the reported SNARC effect is expressed in the early or late (or both) stages of a goal-directed reaching trajectory. Results for RT produced a reliable SNARC effect whereas results for MT produced a reversed-SNARC effect that was attributed to the deceleration phase of reach trajectories. More specifically, left space reaches cued by low numbers produced shorter RTs than high number counterparts and were associated with longer MTs (the converse was true of right space reaches). We have interpreted these results in terms of a spatial–numerical bias influencing a trade-off between the temporal properties of movement planning and execution mechanisms.
Effect of exercise training on vascular endothelial function in patients with stable coronary artery disease: a randomized controlled trial
Authors: Luk Ting-Hin , Dai Yuk-Ling , Siu Chung-Wah , Yiu Kai-Hang , Chan Hiu-Ting , Lee Stephen WL , Li Sheung-Wai , Fong Bonnie , Wong Wai-Keung , Tam Sidney , Lau Chu-Pak , Tse Hung-Fat 
Published: July 2011

Background: We aim to investigate the effect of exercise training on endothelial function and exercise capacity in patients with coronary artery disease. Methods and results: A randomized, controlled trial was conducted to determine the effects of an 8-week exercise training programme ( n = 32) vs. controls ( n = 32) on brachial flow-mediated dilation (FMD) in patients with stable CAD. After 8 weeks, patients received exercise training had significant improvements in FMD (1.84%, p = 0.002) and exercise capacity (2.04 metabolic equivalents, p < 0.001) compared with controls. The change in FMD correlated inversely with baseline FMD ( r = −0.41, p = 0.001) and positively with the increase in exercise capacity ( r = 0.35, p = 0.005). After adjusting for confounders, every 1 metabolic equivalent increase in exercise capacity was associated with 0.55% increase in FMD. Furthermore, patients received exercise training had significantly increased high-density lipoprotein cholesterol and decreased diastolic blood pressure and resting heart rate compared with controls. However, exercise training did not alter high-sensitivity C-reactive protein, oxidative stress measured as superoxide dismutase and 8-isoprostane, and CD34/KDR + endothelial progenitor cell count. Subgroup analysis showed that FMD was significantly improved only in CAD patients with baseline low exercise capacity (<median value of 7.65 metabolic equivalents, p = 0.004) but not in those with normal exercise capacity. Conclusion: Exercise training improved FMD and exercise capacity in stable CAD patients independent of the changes in inflammation, oxidative stress, or endothelial progenitor cells. The beneficial effects of exercise training on FMD and exercise capacity are inter-related, and more pronounced in those with baseline impaired exercise capacity.
Relation between thyroid-stimulating hormone and the occurrence of cardiovascular events and mortality in patients with manifest vascular diseases
Authors: Westerink Jan , van der Graaf Yolanda , Faber Daniël R , Spiering Wilko , Visseren Frank LJ 
Published: July 2011

Aims: To investigate whether levels of thyroid-stimulating hormone (TSH) within the normal range are associated with an increased risk of new vascular events and mortality in patients with clinical manifest vascular diseases and whether this relation is influenced by adiposity. Methods and results: Prospective cohort study in 2443 patients (1790 men and 653 women) with clinical manifest vascular disease and TSH levels in the normal range. Median follow up was 2.7 (interquartile range 1.4–3.9) years. Clinical endpoints of interest were: myocardial infarction, stroke, vascular death, and all-cause mortality. In patients with manifest vascular disease, the prevalence of (subclinical) hypothyroidism was 5.7%, while 3.6% had (subclinical) hyperthyroidism. An increase in 1 unit of TSH was associated with a 33% higher risk (HR 1.33; 95% CI 1.03–1.73) for the occurrence of myocardial infarction, adjusted for age, gender, renal function, and smoking. In patients with a body mass index (BMI) below the median of 26.7 kg/m2 the HR per unit TSH for myocardial infarction was 1.55 (95% CI 1.08–2.21) compared to 1.18 (95% CI 0.81–1.71) in patients with a BMI ≥26.7 kg/m2. Visceral adipose tissue thickness below the median (≤8.8 cm) was associated with higher HR per unit TSH for myocardial infarction (HR 1.69; 95% CI 1.21–2.35) compared to visceral adipose tissue thickness >8.9 cm (HR 1.00; 95% CI 0.66–1.49). There was no relation between TSH and risk of stroke, vascular death, the combined endpoint, or all-cause mortality. Conclusion: Higher TSH levels within the normal range are associated with an increased risk of myocardial infarction, in patients with clinical manifest vascular disease. This relation is most prominent in patients without visceral obesity.
Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis
Authors: Libregts Sten F. , Gutiérrez Laura , de Bruin Alexander M. , Wensveen Felix M. , Papadopoulos Petros , van Ijcken Wilfred , Özgür Zeliha , Philipsen Sjaak , Nolte Martijn A. 
Published: July 2011

AbstractAnemia of chronic disease is a complication accompanying many inflammatory diseases. The proinflammatory cytokine IFN-γ has been implicated in this form of anemia, but the underlying mechanism remains unclear. Here we describe a novel mouse model for anemia of chronic disease, in which enhanced CD27-mediated costimulation strongly increases the formation of IFN-γ–producing effector T cells, leading to a progressive anemia. We demonstrate that the anemia in these mice is fully dependent on IFN-γ and that this cytokine reduces both the life span and the formation of red blood cells. Molecular analysis revealed that IFN-γ induces expression of the transcription factors of interferon regulatory factor-1 (IRF-1) and PU.1 in both murine and human erythroid precursors. We found that, on IFN-γ stimulation, IRF-1 binds to the promoter of SPI.1 (PU.1) and induces PU.1 expression, leading to inhibition of erythropoiesis. Notably, down-regulation of either IRF-1 or PU.1 expression is sufficient to overcome IFN-γ–induced inhibition of erythropoiesis. These findings reveal a molecular mechanism by which chronic exposure to IFN-γ induces anemia.
Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas
Authors: Witzig Thomas E. , Tang Hui , Micallef Ivana N. M. , Ansell Stephen M. , Link Brian K. , Inwards David J. , Porrata Luis F. , Johnston Patrick B. , Colgan Joseph P. , Markovic Svetomir N. , Nowakowski Grzegorz S. , Thompson Carrie A. , Allmer Cristine , Maurer Matthew J. , Gupta Mamta , Weiner George , Hohl Ray , Kurtin Paul J. , Ding Husheng , Loegering David , Schneider Paula , Peterson Kevin , Habermann Thomas M. , Kaufmann Scott H. 
Published: July 2011

AbstractA phase 2 study of the oral farnesyltransferase inhibitor tipifarnib was conducted in 93 adult patients with relapsed or refractory lymphoma. Patients received tipifarnib 300 mg twice daily on days 1-21 of each 28-day cycle. The median number of prior therapies was 5 (range, 1-17). For the aggressive B-cell, indolent B-cell, and T-cell and Hodgkin lymphoma (HL/T) groups, the response rates were 17% (7/42), 7% (1/15), and 31% (11/36), respectively. Of the 19 responders, 7 were diffuse large B-cell non-Hodgkin lymphoma (NHL), 7 T-cell NHL, 1 follicular grade 2, and 4 HL. The median response duration for the 19 responders was 7.2 months (mean, 15.8 months; range, 1.8-62), and 5 patients in the HL/T group are still receiving treatment at 29-64+ months. The grade 3/4 toxicities observed were fatigue and reversible myelosuppression. Correlative studies suggest that Bim and Bcl-2 should be examined as potential predictors of response in future studies. These results indicate that tipifarnib has activity in lymphoma, particularly in heavily pretreated HL/T types, with little activity in follicular NHL. In view of its excellent toxicity profile and novel mechanism of action, further studies in combination with other agents appear warranted. This trial is registered at www.clinicaltrials.gov as #NCT00082888.
Splenic marginal zone lymphoma with VH1-02 gene rearrangement expresses poly- and self-reactive antibodies with similar reactivity
Authors: Warsame Abdirashid A. , Aasheim Hans-Christian , Nustad Kjell , Trøen Gunhild , Tierens Anne , Wang Vivian , Randen Ulla , Dong Hiep P. , Heim Sverre , Brech Andreas , Delabie Jan 
Published: July 2011

AbstractOne-third of all splenic marginal zone lymphomas (SMZL) use the IgH VH1-02 gene. These cases are usually not associated with hepatitis C virus infection. Of interest, the rearranged VH1-02 genes display similar complementarity determining regions 3, a finding confirmed by our study. The latter suggests that these SMZL may produce antibodies with similar reactivity. We produced recombinant antibodies from 5 SMZL cases with VH1-02 gene rearrangement to study the binding reactivity of these antibodies. Surprisingly, the recombinant antibodies demonstrated poly- and self-reactivity as demonstrated by their reactivity with nuclear, cytoplasmic, as well as membranous antigens expressed by human cells and by reactivity with human serum. This polyreactivity was specific as demonstrated by ELISA. The antibodies did not react with proteins on the cell surface that are induced by apoptosis as shown for antibodies produced by chronic lymphatic leukemia with VH1-02 gene rearrangement. The results indicate that a common subset of SMZL arises from polyreactive B cells, a subset of marginal zone B cells that are important in the immunologic defense against infection.