bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative magnetic resonance imaging of subcutaneous adipose tissue
Authors: Gensanne D. , Josse G. , Theunis J. , Lagarde J. M. , Vincensini D. 
Published: August 2008

Background/purpose: Quantitative transverse relaxation time (T2) magnetic resonance (MR) imaging has been used with the aim to characterize subcutaneous adipose tissue. Protons in adipose tissue have a fast exchange behavior giving bi‐component transverse relaxation processes with short and long relaxation time values depending on the tissue properties.Methods: MR images were acquired on a 1 T Siemens MR scan using a multi‐spin‐echo sequence. A high sensitive surface coil, enabling low noise MR images with voxel size of 10 mm3, was used for performing accurate quantitative T2 imaging. These acquisition parameters were determined by a preliminary study performed on an oil phantom known to be a valuable model for mimicking in vivo adipose tissue. In vivo study of the thigh adipose tissue was carried out on 30 volunteers. 20 women with various clinically diagnosed cellulite grades and 10 males, among them five showed overweight. Tissue characterization was finally performed through the analysis of the T2 distributions.Results: Phantom study showed that improvements in the precision in T2 measurement are obtained at the expense of the spatial resolution. Uncertainties in T2 measurements are three times lower by considering a region of interest of 3 × 3 pixels compared with a pixel by pixel analysis.The in vivo study showed that women groups present higher mean short T2S component values than men. Histogram of T2 distribution showed that the maximum amplitude is observed at a lower value for the overweight men group. In addition, larger values around the septae were visualized on the long relaxation time images.Conclusions: This study shows that precise T2 map of adipose tissue can be computed. The balance between precision and spatial resolution is examined. Preliminary results relative to tissue organization and to difference between clinical groups proves the potential of the quantitative MRI.
Characterization of the mechanical properties of a dermal equivalent compared with human skin in vivo by indentation and static friction tests
Authors: Zahouani H. , Pailler‐Mattei C. , Sohm B. , Vargiolu R. , Cenizo V. , Debret R. 
Published: August 2008

Background/aims: The study of changes in skin structure with age is becoming all the more important with the increase in life. The atrophy that occurs during aging is accompanied by more profound changes, with a loss of organization within the elastic collagen network and alterations in the basal elements. The aim of this study is to present a method to determine the mechanical properties of total human skin in vivo compared with dermal equivalents (DEs) using indentation and static friction tests.Methods: A new bio‐tribometer working at a low contact pressure for the characterization the mechanical properties of the skin has been developed. This device, based on indentation and static friction tests, also allows to characterize the skin in vivo and reconstructed DEs in a wide range of light contact forces, stress and strain.Results: This original bio‐tribometer shows the ability to assess the skin elasticity and friction force in a wide range of light normal load (0.5–2 g) and low contact pressure (0.5–2 kPa). The results obtained by this approach show identical values of the Young's modulus E* and the shear modulus G* of six DEs obtained from a 62‐year‐old subject (E*=8.5±1.74 kPa and G*=3.3±0.46 kPa) and in vivo total skin of 20 subjects aged 55 to 70 years (E*=8.3±2.1 kPa, G*=2.8±0.8 kpa).
Linguists as Agents for Social Change
Authors: Charity Anne H. 
Published: August 2008

AbstractIn this article, I examine and promote the role of linguist as agent for social change. I discuss the history and mission of organizations and individual linguists who are dedicated to service through linguistics. I describe the social and community service activities of linguists that may fall just outside of the realm of linguistic scholarship in the most traditional sense. I then provide models for ways in which linguists can become even more socially engaged through social service and public outreach. I highlight the academic sharing and public dissemination of knowledge that linguists already possess as a way for all linguists to be socially active. I then describe my own experiences participating in and teaching service learning‐based research courses.
Levosimendan versus Dobutamine in Heart Failure Patients Treated Chronically with Carvedilol
Authors: Duygu Hamza , Turk Ugur , Ozdogan Oner , Akyuz Serdar , Kirilmaz Bahadir , Alioglu Emin , Gunduz Ramazan , Bozkaya Yasemin Turan , Turkoglu Cuneyt , Payzin Serdar 
Published: August 2008

Introduction: Although beta‐blockers are highly effective in the treatment of heart failure (HF), many patients with HF receiving a beta‐blocker continue to become decompensated and require hospitalization for worsening HF. Levosimendan and dobutamine are used to manage decompensated HF, but their comparative effects on left ventricular (LV) function in patients prescribed beta‐blockers are unknown. Aims: The aim of this study was to compare the effects of dobutamine and levosimendan on LV systolic and diastolic functions in chronic HF patients treated chronically with carvedilol. Forty patients with chronic HF who had NYHA class III to IV symptoms, a LV ejection fraction (LVEF) <40%, and ongoing treatment with carvedilol were enrolled in this randomized (1:1), dobutamine controlled, open‐label study. Before and 24 h after treatment, LVEF, mitral inflow peak E and A wave velocity, E/A ratio, the deceleration time of the E wave (DT), isovolumic relaxation time (IVRT), peak systolic (Sm) and early diastolic (Em) mitral annular velocity, and systolic pulmonary artery pressure (SPAP) were measured by echocardiography. Results: Levosimendan produced a statistically significant increase in LVEF (28 ± 5% vs. 33 ± 3%), Sm (6.5 ± 1.2 cm/s vs. 7.4 ± 0.9 cm/s), DT (120 ± 10 ms vs. 140 ± 15 ms), and Em (7.5 ± 0.4 cm/s vs. 8.1 ± 0.5 cm/s) and significant decrease in E/A ratio (2.1 ± 0.3 vs. 1.7 ± 0.4) and SPAP (55 ± 5 mmHg vs. 40 ± 7 mmHg). No significant change occurred in LV systolic and diastolic function parameters, or SPAP with dobutamine treatment. Levosimendan did not significantly alter the heart rate (72 ± 4 bpm vs. 70 ± 3 bpm), systolic (105 ± 5 mmHg vs. 102 ± 4 mmHg), or diastolic blood pressure (85 ± 5 mmHg vs. 83 ± 5 mmHg) whereas with dobutamine treatment, all these parameters significantly increased. Conclusions: Dobutamine and levosimendan have different effects on LV functions in patients treated chronically with carvedilol. These differences should be considered when selecting inotropic therapy for decompensated HF receiving long‐term carvedilol.
Assessment of Arterial Stiffness, A Translational Medicine Biomarker System for Evaluation of Vascular Risk
Authors: Wang Xinkang , Keith Jr James C. , Struthers Allan D. , Feuerstein Giora Z. 
Published: August 2008

Aims: Stiffening of the large arteries is a common feature of aging and is exacerbated by a number of disorders such as hypertension, diabetes, and renal disease. Arterial stiffening is recognized as an important and independent risk factor for cardiovascular events. This article will provide a comprehensive review of the recent advance on assessment of arterial stiffness as a translational medicine biomarker for cardiovascular risk. Discussions: The key topics related to the mechanisms of arterial stiffness, the methodologies commonly used to measure arterial stiffness, and the potential therapeutic strategies are discussed. A number of factors are associated with arterial stiffness and may even contribute to it, including endothelial dysfunction, altered vascular smooth muscle cell (SMC) function, vascular inflammation, and genetic determinants, which overlap in a large degree with atherosclerosis. Arterial stiffness is represented by biomarkers that can be measured noninvasively in large populations. The most commonly used methodologies include pulse wave velocity (PWV), relating change in vessel diameter (or area) to distending pressure, arterial pulse waveform analysis, and ambulatory arterial stiffness index (AASI). The advantages and limitations of these key methodologies for monitoring arterial stiffness are reviewed in this article. In addition, the potential utility of arterial stiffness as a translational medicine surrogate biomarker for evaluation of new potentially vascular protective drugs is evaluated. Conclusions: Assessment of arterial stiffness is a sensitive and useful biomarker of cardiovascular risk because of its underlying pathophysiological mechanisms. PWV is an emerging biomarker useful for reflecting risk stratification of patients and for assessing pharmacodynamic effects and efficacy in clinical studies.
Nebivolol: A Highly Selective β1‐Adrenergic Receptor Blocker That Causes Vasodilation by Increasing Nitric Oxide
Authors: Gupta Sandeep , Wright Harold M. 
Published: August 2008

Nebivolol (Bystolic®) is a cardioselective beta 1 (β1)‐adrenergic receptor blocker with endothelium‐dependent vasodilating properties. The endothelium‐dependent relaxation induced by nebivolol is blocked by inhibitors of nitric oxide synthase (NOS) and guanylate cyclase. Nebivolol also increasesin vitroandin vivonitric oxide (NO), which is an essential signaling molecule involved in the maintenance of cardiovascular homeostasis.This review summarizes the data involving nebivolol and NO bioavailability. Endothelium‐dependent relaxation of blood vessels, which is impaired in hypertensive animals and humans, is reversed by nebivolol treatment. Animals exhibiting endothelial dysfunction also show an improvement in NO–cyclic guanosine monophosphate (cGMP) signaling and an increase in NO bioavailability when treated with nebivolol. When blood vessel and cultured endothelial cells from hypertensive animals are treated with nebivolol, there is a decrease in superoxide production and an increase in the expression and activity of endothelial NOS (eNOS). As a result of the increased bioavailability of NO, nebivolol also increasesin vivoarterial distensibility, glomerular filtration rate, and renal plasma flow. In normotensive volunteers, nebivolol infusion increases the forearm blood flow, an effect that is blocked by inhibitors of NOS and restored by the NOS substrate, L‐arginine. In hypertensive patients, chronic treatment with nebivolol improves endothelium‐dependent vasodilation induced by acetylcholine and shear stress and reverses endothelium‐dependent vasoconstriction. Furthermore, nebivolol displays distinct hemodynamic properties in patients that include improvements in stroke volume and a decrease in peripheral vascular resistance.These studies demonstrate that nebivolol produces endothelium‐dependent vasodilation by increasing NO release, decreasing oxidative stress to increase NO bioavailability, or both. The NO‐dependent vasodilatory action of nebivolol, coupled with its high β1‐adrenergic receptor selectivity, is unique among the clinically available β‐blockers and contributes to its efficacy and improved tolerability (e.g., less fatigue and sexual dysfunction) as an antihypertensive agent.
BMI-1 Promotes Ewing Sarcoma Tumorigenicity Independent ofCDKN2ARepression
Authors: Douglas Dorothea , Hsu Jessie Hao-Ru , Hung Long , Cooper Aaron , Abdueva Diana , van Doorninck John , Peng Grace , Shimada Hiro , Triche Timothy J. , Lawlor Elizabeth R. 
Published: August 2008

AbstractDeregulation of the polycomb group gene BMI-1 is implicated in the pathogenesis of many human cancers. In this study, we have investigated if the Ewing sarcoma family of tumors (ESFT) expresses BMI-1 and whether it functions as an oncogene in this highly aggressive group of bone and soft tissue tumors. Our data show that BMI-1 is highly expressed by ESFT cells and that, although it does not significantly affect proliferation or survival, BMI-1 actively promotes anchorage-independent growth in vitro and tumorigenicity in vivo. Moreover, we find that BMI-1 promotes the tumorigenicity of both p16 wild-type and p16-null cell lines, demonstrating that the mechanism of BMI-1 oncogenic function in ESFT is, at least in part, independent of CDKN2A repression. Expression profiling studies of ESFT cells following BMI-1 knockdown reveal that BMI-1 regulates the expression of hundreds of downstream target genes including, in particular, genes involved in both differentiation and development as well as cell-cell and cell-matrix adhesion. Gain and loss of function assays confirm that BMI-1 represses the expression of the adhesion-associated basement membrane protein nidogen 1. In addition, although BMI-1 promotes ESFT adhesion, nidogen 1 inhibits cellular adhesion in vitro. Together, these data support a pivotal role for BMI-1 ESFT pathogenesis and suggest that its oncogenic function in these tumors is in part mediated through modulation of adhesion pathways. [Cancer Res 2008;68(16):6507–15]
Centrosomal PKCβII and Pericentrin Are Critical for Human Prostate Cancer Growth and Angiogenesis
Authors: Kim Jeewon , Choi Yoon-La , Vallentin Alice , Hunrichs Ben S. , Hellerstein Marc K. , Peehl Donna M. , Mochly-Rosen Daria 
Published: August 2008

AbstractAngiogenesis is critical in the progression of prostate cancer. However, the interplay between the proliferation kinetics of tumor endothelial cells (angiogenesis) and tumor cells has not been investigated. Also, protein kinase C (PKC) regulates various aspects of tumor cell growth, but its role in prostate cancer has not been investigated in detail. Here, we found that the proliferation rates of endothelial and tumor cells oscillate asynchronously during the growth of human prostate cancer xenografts. Furthermore, our analyses suggest that PKCβII was activated during increased angiogenesis and that PKCβII plays a key role in the proliferation of endothelial cells and tumor cells in human prostate cancer; treatment with a PKCβII-selective inhibitor, βIIV5-3, reduced angiogenesis and tumor cell proliferation. We also find a unique effect of PKCβII inhibition on normalizing pericentrin (a protein regulating cytokinesis), especially in endothelial cells as well as in tumor cells. PKCβII inhibition reduced the level and mislocalization of pericentrin and normalized microtubule organization in the tumor endothelial cells. Although pericentrin has been known to be up-regulated in epithelial cells of prostate cancers, its level in tumor endothelium has not been studied in detail. We found that pericentrin is up-regulated in human tumor endothelium compared with endothelium adjacent to normal glands in tissues from prostate cancer patients. Our results suggest that a PKCβII inhibitor such as βIIV5-3 may be used to reduce prostate cancer growth by targeting both angiogenesis and tumor cell growth. [Cancer Res 2008;68(16):6831–9]
Phosphatidylcholine-Specific Phospholipase C Activation in Epithelial Ovarian Cancer Cells
Authors: Spadaro Francesca , Ramoni Carlo , Mezzanzanica Delia , Miotti Silvia , Alberti Paola , Cecchetti Serena , Iorio Egidio , Dolo Vincenza , Canevari Silvana , Podo Franca 
Published: August 2008

AbstractElucidation of the mechanisms responsible for aberrant phosphatidylcholine (PC) metabolism in cancer cells may allow identification of novel biomarkers of tumor progression and design of new targeted anticancer therapies. We recently reported up-regulation of PC-specific phospholipases in epithelial ovarian cancer cells (EOC) compared with nontumoral (normal or immortalized) counterparts (EONT). In the present study, we focused, in the same cell systems, on levels, subcellular localization, and activity of PC-specific phospholipase C (PC-PLC), for which a key role in cell proliferation, differentiation, and apoptosis has been shown in several mammalian cells. A 66-kDa PC-PLC isoform, detected in nuclear and cytoplasmic compartments of both EOC and EONT cells, accumulated on the external plasma membrane of cancer cells only, where it colocalized with β1 integrin, in nonraft membrane domains. PC-PLC activity was 3-fold higher in total cell lysates and 5-fold higher in membrane-enriched fractions of EOC compared with EONT cells. Serum deprivation induced in EOC, but not in EONT, cells a 3-fold decrease in PC-PLC activity, associated with a 40% drop in S-phase fraction. The recovery of both variables to their original levels in serum-restimulated (or lysophosphatidic acid–restimulated) EOC cells was strongly delayed, for at least 24 h, in the presence of the PC-PLC inhibitor tricyclodecan-9-yl-potassium xanthate (D609). The S-phase of serum-restimulated EONT cells was not sensitive to D609. These findings warrant further investigations on the role of PC-PLC and on the effects of its inhibition on the pathways responsible for constitutive EOC cell stimulation and cell proliferation. [Cancer Res 2008;68(16):6541–9]
Down-regulation of Phospho-Akt Is a Major Molecular Determinant of Bortezomib-Induced Apoptosis in Hepatocellular Carcinoma Cells
Authors: Chen Kuen-Feng , Yeh Pei-Yen , Yeh Kun-Huei , Lu Yen-Shen , Huang Shang-Yi , Cheng Ann-Lii 
Published: August 2008

Abstract
Bortezomib, a proteasome inhibitor, has been clinically approved for the treatment of myeloma and lymphoma. Here, we report a differential effect of bortezomib on apoptosis in four hepatocellular carcinoma (HCC) cell lines and identify the major molecular event that determines sensitivity. Although bortezomib inhibited proteasome activity to a similar extent in all HCC cell lines, it showed differential effects on their viability: Huh-7 (IC50 196 nmol/L), Sk-Hep1 (IC50 180 nmol/L), Hep3B (IC50 112 nmol/L), and resistant PLC5 (IC50 &gt;1,000 nmol/L). Bortezomib caused cell cycle arrest at G2-M phase in all HCC cells tested whereas apoptotic induction was found only in sensitive cells but not in PLC5 cells. No significant bortezomib-induced NF-κB changes were noted in Huh-7 and PLC5. Bortezomib down-regulated phospho-Akt (P-Akt) in a dose- and time-dependent manner in all sensitive HCC cells whereas no alterations of P-Akt were found in PLC5. Down-regulation of Akt1 by small interference RNA overcame the apoptotic resistance to bortezomib in PLC5 cells, but a constitutively activated Akt1 protected Huh-7 cells from bortezomib-induced apoptosis. Furthermore, bortezomib showed suppression of tumor growth with down-regulation of P-Akt in Huh-7 tumors but not in PLC5 tumors. Down-regulation of P-Akt represents a major molecular event of bortezomib-induced apoptosis in HCC cell lines and may be a biomarker for predicting clinical response to HCC treatment. Targeting Akt signaling overcomes drug resistance to bortezomib in HCC cells, which provides a new approach for the combinational therapy of HCC. [Cancer Res 2008;68(16):6698–707]
Disturbed Patterns of Immunocompetent Cells in Usual-Type Vulvar Intraepithelial Neoplasia
Authors: van Seters Manon , Beckmann Ilse , Heijmans-Antonissen Claudia , van Beurden Marc , Ewing Patricia C. , Zijlstra Freek J. , Helmerhorst Theo J.M. , KleinJan Alex 
Published: August 2008

Abstract
Genital infection with human papillomavirus (HPV) is usually transient, as the immune system is capable of eliminating the virus. When immunity “fails” and the infection persists, vulvar intraepithelial neoplasia (VIN) may develop. In this study, we examined the distribution of inflammatory cells in 51 patients with HPV-associated usual-type VIN and in 19 healthy controls. Frozen vulvar tissue samples were tested for the presence of HPV-DNA, and immunohistochemical staining for the markers CD1a, CD207, CD208, CD123/CD11c, CD94, CD4, CD8, and CD25/HLA-DR was performed. Cells were counted in both the epidermis and dermis over at least 2 mm of basal membrane length. In the epidermis of VIN patients, CD1a+ and CD207+ (Langerin) dendritic cells (DC) and CD8+ T cells were significantly lower than in controls, whereas the number of CD123+/CD11c− plasmacytoid DCs (pDC) was significantly increased. No significant changes were observed for CD208+ DCs, CD94+ natural killer (NK) cells, CD4+ T cells, and CD25+/HLA-DR+ regulatory T cells. In the dermis of VIN patients, elevated numbers of CD208+, CD123+/CD11c−, CD94+, CD4+, CD8+, and CD25+/HLA-DR+ cells were observed when compared with healthy controls. The numbers of CD1a+ and CD207+ DCs were not different between groups. In summary, high-risk HPV–related usual-type VIN lesions are characterized by an immunosuppressive state in the epidermis, showing a reduction of immature myeloid DCs (mDC) and CD8+ T cells. In the dermis, inflammatory activation is reflected by the influx of mature mDCs and pDCs, NK cells, and T cells, suggesting that the cellular immune response on viral HPV infection occurs in the dermis of VIN patients. [Cancer Res 2008;68(16):6617–22]
Chromosome 17q12 Variants Contribute to Risk of Early-Onset Prostate Cancer
Authors: Levin Albert M. , Machiela Mitchell J. , Zuhlke Kimberly A. , Ray Anna M. , Cooney Kathleen A. , Douglas Julie A. 
Published: August 2008

Abstract
In a recent genome-wide association study by Gudmundsson and colleagues, two prostate cancer susceptibility loci were identified on chromosome 17q. The first locus, at 17q12, was distinguished by two intronic single-nucleotide polymorphisms (SNPs) in the TCF2 gene (rs4430796 and rs7501939). The second locus was in a gene-poor region of 17q24, where the strongest evidence of association was for SNP rs1859962. To determine if these loci were also associated with hereditary prostate cancer, we genotyped them in a family-based association sample of 403 non-Hispanic white families, including 1,015 men with and without prostate cancer. SNPs rs4430796 and rs7501939, which were in strong linkage disequilibrium (r2 = 0.68), showed the strongest evidence of prostate cancer association. Using a family-based association test, the A allele of SNP rs4430796 was overtransmitted to affected men (P = 0.006), with an odds ratio of 1.40 (95% confidence interval, 1.09–1.81) under an additive genetic model. Notably, rs4430796 was significantly associated with prostate cancer among men diagnosed at an early (&lt;50 years) but not later age (P = 0.006 versus P = 0.118). Our results confirm the prostate cancer association with SNPs on chromosome 17q12 initially reported by Gudmundsson and colleagues. In addition, our results suggest that the increased risk associated with these SNPs is approximately doubled in individuals predisposed to develop early-onset disease. Importantly, these SNPs do not account for a significant portion of our prior prostate cancer linkage evidence on chromosome 17. Thus, there likely exist one or more additional independent prostate cancer susceptibility loci in this region. [Cancer Res 2008;68(16):6492–5]