bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allele-specific transcription of the PAI-1 gene in human astrocytes
Authors: Hultman Karin , Tjärnlund-Wolf Anna , Odeberg Jacob , Eriksson Per , Jern Christina 
Published: August 2010

SummaryThe 4G allele of the PAI-1 –675(4G/5G) insertion/deletion promoter polymorphism has been associated with elevated plasma levels of PAI-1 and an increased risk of myocardial infarction. However, this allele has also been associated with a reduced risk of ischaemic stroke. In the brain, PAI-1 is mainly produced by astrocytes, and can reduce the neurotoxic effects exerted by tissue-type plasminogen activator during pathophysiologic conditions. The aim of the present study was to investigate whether the PAI-1 –675(4G/5G) polymorphism and the linked –844A/G polymorphism affect transcriptional activity of the PAI-1 gene in human astrocytes. Haplotype chromatin immunoprecipitation (haploChIP) was used in order to quantify allele-specific promoter activity in heterozygous cells. Protein-DNA interactions were investigated by electrophoretic mobility shift assay (EMSA). A clear allele-specific difference in PAI-1 gene expression was observed in astrocytes, where the haplotype containing the 4G and the –844A alleles was associated with higher transcriptional activity compared to the 5G and –844G-containing haplotype. EMSA revealed an allele-specific binding of nuclear proteins to the 4G/5G site as well as to the –844A/G site. Supershift experiments identified specific binding of the transcription factors Elf-1 and Elk-1 to the –844G allele. The relative impact of the different sites on allele-specific PAI-1 promoter activity remains to be determined. We demonstrate that common polymorphisms within the PAI-1 promoter affect transcriptional activity of the PAI-1 gene in human astrocytes, thus providing a possible molecular genetic mechanism behind the association between PAI-1 promoter variants and ischaemic stroke.
Effect of apixaban, an oral and direct factor Xa inhibitor, on coagulation activity biomarkers following acute coronary syndrome
Authors: Alexander John , Newby L. Kristin , Yang Hongqiu , Barrett Yuchen , Mohan Puneet , Wang Jessie , Harrington Robert , Wallentin Lars , Becker Richard 
Published: August 2010

SummaryApixaban is an oral, direct factor Xa inhibitor under development for secondary prevention in acute coronary syndrome (ACS). Apixaban‘s effect on D-dimer and prothrombin fragment 1.2 (F1.2) (coagulation activity biomarkers ) was determined in a randomised, double-blinded, placebo-controlled, phase 2 study. Patients (n=1,715) with either ST-segment elevation or non-ST-segment elevation ACS received either placebo or apixaban 2.5 mg twice daily, 10 mg once daily, 10 mg twice daily or 20 mg once daily for six months. Samples were obtained at baseline (before study drug administration), week 3 and week 26. Apixaban plasma concentrations were measured directly by liquid chromatography/mass spectometry, and anti-Xa activity was determined using apixaban as a reference standard. D-dimer and F 1.2 were measured using ELISA-based methods. Most patients had elevated D-dimer and F1.2 levels at baseline. Both coagulation activity biomarkers decreased by week 3 in all treatment groups, but to a greater degree with apixaban than placebo (p<0.001). In a multivariable analysis, apixaban was independently associated with a change in biomarkers over time (p<0.0001). While the overall decrease did not differ significantly among the three highest apixaban doses, F1.2 was suppressed more rapidly by the 10 mg once daily than the 2.5 mg twice daily dose (p<0.05). There was a strong and direct relationship between apixaban plasma concentrations and anti-Xa-apixaban levels, and an inverse relationship for both measures with coagulation activity biomarkers. In conclusion, the oral direct factor Xa inhibitor apixaban significantly reduced coagulation activity biomarkers among patients with ACS. The 10 mg once daily dose reduced thrombin generation (F 1.2) and fibrin formation (D-dimer) more rapidly and robustly than the 2.5 mg twice daily dose. The effect on both D-dimer and F 1.2 was apixaban concentration-and factor Xa inhibition dependent, durable and provided general guidance for dose selection in phase 3 investigation.
BF0801, a novel adenine derivative, inhibits platelet activation via phosphodiesterase inhibition and P2Y12 antagonism
Authors: Zhang Si , Hu Liang , Du Hongguang , Guo Yan , Zhang Yan , Niu Haixia , Jin Jianguo , Zhang Jian , Liu Junling , Zhang Xiaohui , Kunapuli Satya , Ding Zhongren 
Published: August 2010

SummaryThough antiplatelet drugs are proven beneficial to patients with coronary heart disease and stroke, more effective and safer antiplatelet drugs are still needed. In this study we report the antiplatelet effects and mechanism of BF0801, a novel adenine derivative. BF0801 dramatically inhibited platelet aggregation and ATP release induced by ADP, 2MeSADP, AYPGKF, SFLLRN or convulxin without affecting shape change in vitro. It also potentiated the inhibitory effects of adenosine-based P2Y12 antagonist AR-C69931MX or phosphodiesterase (PDE) inhibitor IBMX on platelet aggregation. The cAMP levels in both resting and forskolin-stimulated platelets were increased by BF0801 suggesting its PDE inhibitor activity, which is further confirmed by the concentration-dependent suppression of BF0801 on the native and recombinant PDE. Similar to AR-C69931MX, BF0801 drastically inhibited 2MeSADP-induced adenylyl cyclase inhibition in platelets indicating its P2Y12 antagonism activity, which is substantiated by the inhibition of BF0801 on the interaction between ADP and P2Y12 receptor expressed in CHO-K1 cells measured by atomic force microscopy. Moreover, we confirmed the antiplatelet effects of BF0801 using platelets from rats intravenously given BF0801. In summary, for the first time we developed a novel adenine derivative bearing dual activities of PDE inhibition and P2Y12 antagonism, which may have therapeutic advantage as a potential antithrombotic drug.
Representation of Action in Occipito-temporal Cortex
Authors: Wiggett Alison J. , Downing Paul E. 
Published: August 2010

Abstract
A fundamental question for social cognitive neuroscience is how and where in the brain the identities and actions of others are represented. Here we present a replication and extension of a study by Kable and Chatterjee [Kable, J. W., & Chatterjee, A. Specificity of action representations in the lateral occipito-temporal cortex. Journal of Cognitive Neuroscience, 18, 1498–1517, 2006] examining the role of occipito-temporal cortex in these processes. We presented full-cue movies of actors performing whole-body actions and used fMRI to test for action- and identity-specific adaptation effects. We examined a series of functionally defined regions, including the extrastriate and fusiform body areas, the fusiform face area, the parahippocampal place area, the lateral occipital complex, the right posterior superior temporal sulcus, and motion-selective area hMT+. These regions were analyzed with both standard univariate measures as well as multivoxel pattern analyses. Additionally, we performed whole-brain tests for significant adaptation effects. We found significant action-specific adaptation in many areas, but no evidence for identity-specific adaptation. We argue that this finding could be explained by differences in the familiarity of the stimuli presented: The actions shown were familiar but the actors performing the actions were unfamiliar. However, in contrast to previous findings, we found that the action adaptation effect could not be conclusively tied to specific functionally defined regions. Instead, our results suggest that the adaptation to previously seen actions across identities is a widespread effect, evident across lateral and ventral occipito-temporal cortex.
How I treat elderly patients with diffuse large B-cell lymphoma
Authors: Pfreundschuh Michael 
Published: August 2010

AbstractEnormous progress has been made in the treatment of diffuse large B-cell lymphoma (DLBCL), mostly due to the anti-CD20 antibody rituximab. More than 50% of elderly DLBCL patients can be expected to be cured by modern immunochemotherapy. The standard chemotherapy partner of rituximab is the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen. Elderly patients need particular attention and thorough evaluation if they are suited for the standard treatment or if they are candidates for palliative treatment. Rigorous supportive care including anti-infectious prophylaxis and growth factor support are mandatory. Whether there is still a role of additive radiotherapy in the R-CHOP era is under debate. While further intensification of chemotherapy might hardly be feasible in elderly patients, dose and schedule of rituximab appear to be optimizable. Patients failing after R-CHOP are a particular challenge as are frail patients who are not fit enough for R-CHOP. Further progress can be expected from novel antibodies and small molecules that interfere with signal transduction pathways essential for the survival of the lymphoma cell. To achieve this goal, prospective trials with large numbers of patients are necessary for which the continuous commitment of patients and physicians is indispensable.
Commitment of chondrogenic precursors of the avian scapula takes place after epithelial-mesenchymal transition of the dermomyotome
Authors: Wang Baigang , Pu Qin , De Raja , Patel Ketan , Christ Bodo , Wilting Jörg , Huang Ruijin 
Published: August 2010

Abstract
Background
Cells of the epithelially organised dermomyotome are traditionally believed to give rise to skeletal muscle and dermis. We have previously shown that the dermomyotome can undergo epithelial-mesenchymal transition (EMT) and give rise to chondrogenic cells, which go on to form the scapula blade in birds. At present we have little understanding regarding the issue of when the chondrogenic fate of dermomyotomal cells is determined. Using quail-chick grafting experiments, we investigated whether scapula precursor cells are committed to a chondrogenic fate while in an epithelial state or whether commitment is established after EMT.

Results
We show that the hypaxial dermomyotome, which normally forms the scapula, does not generate cartilaginous tissue after it is grafted to the epaxial domain. In contrast engraftment of the epaxial dermomyotome to the hypaxial domain gives rise to scapula-like cartilage. However, the hypaxial sub-ectodermal mesenchyme (SEM), which originates from the hypaxial dermomyotome after EMT, generates cartilaginous elements in the epaxial domain, whereas in reciprocal grafting experiments, the epaxial SEM cannot form cartilage in the hypaxial domain.

Conclusions
We suggest that the epithelial cells of the dermomyotome are not committed to the chondrogenic lineage. Commitment to this lineage occurs after it has undergone EMT to form the sub-ectodermal mesenchyme.
EGF regulates survivin stability through the Raf-1/ERK pathway in insulin-secreting pancreatic β-cells
Authors: Wang Haijuan , Gambosova Katarina , Cooper Zachary A , Holloway Michael P , Kassai Andrea , Izquierdo Denisse , Cleveland Kelly , Boney Charlotte M , Altura Rachel A 
Published: August 2010

Abstract

Background
Postnatal expansion of the pancreatic β-cell mass is required to maintain glucose homeostasis immediately after birth. This β-cell expansion is regulated by multiple growth factors, including glucose, insulin, insulin-like growth factor (IGF-1) and epidermal growth factor (EGF). These mitogens signal through several downstream pathways (AKT, ERK, STAT3, and JNK) to regulate the survival and proliferation of β-cells. Survivin, an oncofetal protein with both pro-proliferative and anti-apoptotic properties, is a known transcriptional target of both IGF-1 and EGF in cancer cells. Here, we analyzed the effects of the β-cell mitogens IGF-1 and EGF on survivin regulation in the established pancreatic β-cell model cell lines, MIN6 and INS-1 and in primary mouse islets.

Results
In pancreatic β-cells, treatment with glucose, insulin, or EGF increased survivin protein levels at early time points. By contrast, no significant effects on survivin were observed following IGF-1 treatment. EGF-stimulated increases in survivin protein were abrogated in the presence of downstream inhibitors of the Raf-1/MEK/ERK pathway. EGF had no significant effect on survivin transcription however it prolonged the half-life of the survivin protein and stabilized survivin protein levels by inhibiting surviving ubiquitination.

Conclusions
This study defines a novel mechanism of survivin regulation by EGF through the Raf-1/MEK/ERK pathway in pancreatic β-cells, via prolongation of survivin protein half-life and inhibition of the ubiquitin-mediated proteasomal degradation pathway. This mechanism may be important for regulating β-cell expansion after birth.
Mothers and daughters-in-law: a prospective study of informal care-giving arrangements and survival in Japan
Authors: Nishi Akihiro , Tamiya Nanako , Kashiwagi Masayo , Takahashi Hideto , Sato Mikiya , Kawachi Ichiro 
Published: August 2010

Abstract

Background
Daughters-in-law have played an important role in informal care-giving arrangements within East Asian traditional norms. The aim of this study was to measure the impact of daughter-in-law care-giving on the survival of care recipients. We prospectively examined the associations between different types of kinship relationship between the main family caregiver and the care recipient in relation to survival among care recipients.

Methods
A questionnaire was administered to Japanese community-dwelling seniors who were eligible to receive national long-term care insurance (LTCI) community-based services. Among 191 individuals whose informal care-giving arrangement was definitively determined, we observed 58 care recipients receiving care from spouses, 58 from daughters-in-law, 27 from biological daughters, 25 from other relatives, and 23 care recipients living alone.

Results
During 51 months of follow-up from December 2001, 68 care recipients died, 117 survived, and 6 moved. Hazard ratios of each care-giving arrangement were estimated by Cox proportional hazard models adjusted for care recipients' demographic factors, their care needs level based on their physical and cognitive functioning and their service use, caregivers' demographic factors, and household size. The highest risk of mortality was found for female elders receiving care from daughters-in-law (HR 4.15, 95% CI 1.02-16.90) followed by those receiving care from biological daughters (HR 1.64, 95% CI 0.37-7.21), compared to women receiving spousal care. By contrast, male elders receiving care from daughters-in-law tended to live longer than those receiving care from their spouses.

Conclusions
Our finding suggests that there may be a survival "penalty" for older Japanese women who are cared for by their daughters-in-law.
Development and testing of the BONES physical activity survey for young children
Authors: Economos Christina D , Hennessy Erin , Sacheck Jennifer M , Shea M Kyla , Naumova Elena N 
Published: August 2010

Abstract

Background
Weight-bearing and high intensity physical activities are particularly beneficial for stimulating bone growth in children given that bone responds favorably to mechanical load. While it is important to assess the contribution and impact of weight-bearing physical activity on health outcomes, measurement tools that quantify and provide information on these activities separately from overall physical activity are limited. This study describes the development and evaluation of a pictorial physical activity survey (PAS) that measures children's participation and knowledge of high-intensity, weight-bearing ("bone smart") physical activity.

Methods
To test reliability, two identical sets of the PAS were administered on the same day to 41 children (mean age 7.1 ± 0.8 years; 63% female) and compared. To test validity, accelerometry data from 40 children (mean age 7.7 ± 0.8 years; 50% female) were compared to data provided by the PAS. Agreements between categorical and ordinal items were assessed with Kappa statistics; agreements between continuous indices were assessed with Spearman's correlation tests.

Results
The subjects produced reliable results in all 10 physical activity participation items (κ range: 0.36-0.73, all p < 0.05), but less reliable in answering if the physical activities were "bone smart" (κ range: -0.04-0.66). Physical activity indices, including metabolic equivalent time and weight-bearing factors, were significant in test-retest analyses (Spearman's r range: 0.57-0.74, all p < 0.001). Minutes of very vigorous activity from the accelerometer were associated with the self-reported weight-bearing activity, moderate-high, and high activity scores from the PAS (Spearman's r range: 0.47-0.48, all p < 0.01). However, accelerometer counts, counts per minute, and minutes of moderate-vigorous and vigorous activity were not associated with the PAS scores.

Conclusions
Together, the results of these studies suggest that the PAS has acceptable test-retest reliability, but limited validity for early elementary school children. This survey demonstrates a first step towards developing a questionnaire that measures high intensity, weight-bearing activity in schoolchildren.
Combined vascular endothelial growth factor-A and fibroblast growth factor 4 gene transfer improves wound healing in diabetic mice
Authors: Jazwa Agnieszka , Kucharzewska Paulina , Leja Justyna , Zagorska Anna , Sierpniowska Aleksandra , Stepniewski Jacek , Kozakowska Magdalena , Taha Hevidar , Ochiya Takahiro , Derlacz Rafal , Vahakangas Elisa , Yla-Herttuala Seppo , Jozkowicz Alicja , Dulak Jozef 
Published: August 2010

Abstract

Background
Impaired wound healing in diabetes is related to decreased production of growth factors. Hence, gene therapy is considered as promising treatment modality. So far, efforts concentrated on single gene therapy with particular emphasis on vascular endothelial growth factor-A (VEGF-A). However, as multiple proteins are involved in this process it is rational to test new approaches. Therefore, the aim of this study was to investigate whether single AAV vector-mediated simultaneous transfer of VEGF-A and fibroblast growth factor 4 (FGF4) coding sequences will improve the wound healing over the effect of VEGF-A in diabetic (db/db) mice.

Methods
Leptin receptor-deficient db/db mice were randomized to receive intradermal injections of PBS or AAVs carrying β-galactosidase gene (AAV-LacZ), VEGF-A (AAV-VEGF-A), FGF-4 (AAV-FGF4-IRES-GFP) or both therapeutic genes (AAV-FGF4-IRES-VEGF-A). Wound healing kinetics was analyzed until day 21 when all animals were sacrificed for biochemical and histological examination.

Results
Complete wound closure in animals treated with AAV-VEGF-A was achieved earlier (day 19) than in control mice or animals injected with AAV harboring FGF4 (both on day 21). However, the fastest healing was observed in mice injected with bicistronic AAV-FGF4-IRES-VEGF-A vector (day 17). This was paralleled by significantly increased granulation tissue formation, vascularity and dermal matrix deposition. Mechanistically, as shown in vitro, FGF4 stimulated matrix metalloproteinase-9 (MMP-9) and VEGF receptor-1 expression in mouse dermal fibroblasts and when delivered in combination with VEGF-A, enhanced their migration.

Conclusion
Combined gene transfer of VEGF-A and FGF4 can improve reparative processes in the wounded skin of diabetic mice better than single agent treatment.
Feasibility of breast conservation after neoadjuvant taxene based chemotherapy in locally advanced breast cancer: a Prospective Phase I trial
Authors: El-Sayed Mohamed I , Maximous Doaa W , Aboziada Mohamed A , Abdel-Wanis Mostafa E , Mikhail Nabiel NH 
Published: August 2010

Abstract

Background
Neoadjuvant chemotherapy is the standard care for locally advanced breast cancer. Our study aimed at evaluating the feasibility of breast conversation surgery (BCS) after neoadjuvant chemotherapy.

Patients and methods
Forty five patients had stage IIB (except those with T2N1 disease) and stage IIIA were selected to 3 cycles taxane-based neoadjuvant chemotherapy. Patient who had tumours ≤5 cm underwent a tentative BCS while patients who had tumour size >5 cm underwent radical surgery. Negative margin is essential for BCS. Adjuvant chemotherapy and 3-D radiotherapy ± hormonal treatment were given to all patients.

Results
Thirty four patients had BCS. Response to chemotherapy was the only statistically significant factor which influences the BCS. Incidence of local recurrence was 5.9% for patients who had BCS at a median follow up 24 months.

Conclusion
Breast conservation is feasible in selected cases of locally advanced, non metastatic cancer breast. We recommend that patients who have tumour size ≤4 cm after chemotherapy are the best candidates for BCS.
The course of bipolar disorder
Authors: Saunders Kate E. A. , Goodwin Guy M. 
Published: August 2010

SummaryBipolar disorder is arguably a pivotal diagnosis in adult psychiatry bounded by schizophrenia on one side and unipolar depression on the other. It represents a wide spectrum of disorders, all sharing common features of elated and depressed mood. The early descriptions of symptom-free euthymia have long been dismissed and the chronic and enduring deficits associated with the disorder are beginning to be better understood. We review the current literature with regard to the course of the disorder, factors that may influence prognosis and common comorbidities.
Diagnosis and classification of personality disorder: difficulties, their resolution and implications for practice
Authors: Sarkar Jaydip , Duggan Conor 
Published: August 2010

SummaryThere are many difficulties associated with the diagnostic guidelines for personality disorder in the current international classificatory systems such as ICD–10 and DSM–IV. These lead not only to significant overlap with DSM Axis I disorders, resulting in high rates of diagnoses of comorbidities and multiple personality disorders, but also to lack of adequate capture of core personality pathology. The current classifications are also unhelpful in treatment selection, presumably the prime reason for assessing individuals in the first place. In this article we highlight various deficits and inadequacies related to the nosology of the current systems and suggest some strategies for dealing with these. We offer an integrated model of assessing and diagnosing personality disorders. We attempt to demonstrate how using a more integrated approach minimises or even eliminates some of the key problems highlighted in the current systems.
Personality disorder and mental health legislation in the UK
Authors: Thomson Lindsay D. G. 
Published: August 2010

SummaryThis commentary explores the issue of personality disorder and mental health legislation from a UK perspective, highlighting the differences between its four countries and three mental health acts. It discusses data from Scotland that support the contention that the addition of the term ‘personality disorder’ to mental health legislation is not alone sufficient to change current practice. The legislative criterion of risk to others is discussed and the varying responses in the UK to the contentious issue of preventive detention, highly likely to be relevant to serious offenders with personality disorder, are described, including the indeterminate sentence of imprisonment for public protection and the order of lifelong restriction. It is concluded that, regardless of location, care of patients with a primary diagnosis of personality disorder will be driven forward not by legislation but by service development, research and changing attitudes.