bluuebunny/crossref_metadata_2025 huggingface dataset:
Total Decompression of the Facial Nerve – Superior Prelabyrinthine Cell Tracts Approach
Authors: Takeda Taizo , Takebayashi Shinji , Kakigi Akinobu , Nakatani Hiroaki , Hamada Masashi
Published: March 2010

Conclusion: The surgical procedure for the superior prelabyrinthine cell tract approach is described in detail. This approach is a safer and less invasive procedure to totally decompress the facial nerve compared with conventional middle fossa approach. Objective: To develop a new approach to the meatal and labyrinthine segments that does not require a craniotomy. Background: If performed within 2 weeks after the onset of facial palsy, total decompression of the facial nerve enhances the chance of normal or near-normal facial function recovery in cases with massive nerve degeneration. The transmastoid approach and middle fossa approach are usually combined to totally expose the intratemporal facial nerve. However, the middle fossa approach requires a craniotomy in the temporoparietal area. Because of its invasiveness, patients often hesitate to consent to this operation, and as a result the recovery from facial palsy is incomplete. Surgical Procedure: The meatal and labyrinthine segments of the facial nerve are exposed by the superior route via the superior prelabyrinthine cell tracts. Partial resection of the zygoma makes this approach feasible.
Fractalkine-Induced Endothelial Cell Migration Requires MAP Kinase Signaling
Authors: Volin Michael V. , Huynh Nha , Klosowska Karolina , Reyes Rosemary D. , Woods James M.
Published: March 2010

Background/Aims: Angiogenesis is a well-established characteristic in the rheumatoid arthritis (RA) synovial pannus. We have previously demonstrated that fractalkine (Fkn/ CX3CL1) expression is significantly increased in the RA joint and that fractalkine induces angiogenesis. In this work we studied mechanisms through which Fkn functions as an angiogenic mediator. Methods: Human microvascular endothelial cells (HMVECs) and human umbilical vein endothelial cells (HUVECs) were stimulated with Fkn and analyzed by Western blotting or stained with Alexa Fluor® 488 phalloidin for F-actin to characterize the time frame of cytoskeletal rearrangement. Fkn-induced HUVEC chemotaxis was performed in the presence and absence of MAP kinase inhibitors. Results: Phalloidin staining of F-actin revealed significant cytoskeletal rearrangements in HUVECs and HMVECs starting as early as 10 min after Fkn stimulation. Western blotting demonstrated that HUVEC and HMVEC stimulation with Fkn for 1–30 min resulted in phosphorylation of JNK. Fkn also induces significant phosphorylation of Erk 1/2 in HUVECs over a time course ranging from 1 to 15 min. A somewhat similar time course (5–15 min) was detected for Erk 1/2 phosphorylation in HMVECs. Inhibitors of either JNK or Erk 1/2 nearly abolish Fkn-induced HUVEC migration. Conclusions: We demonstrate that Fkn induces significant alterations in cytoskeletal structure and specifically activates the MAP kinases, JNK and Erk 1/2, both of which appear necessary for endothelial cell migration. Our results suggest that the endogenous Fkn present in the RA joint may induce angiogenesis through activation of the JNK and Erk 1/2 pathways.
Distribution of PD-1+ Lymphocytes in Reactive Lymphadenopathies
Authors: Muenst Simone , Dirnhofer Stephan , Tzankov Alexandar
Published: March 2010

Objectives: Programmed death-1 (PD-1) is physiologically expressed by germinal center (GC)-associated helper T cells. It has been proposed that an increase in PD-1+ cells outside GC could indicate pattern I angioimmunoblastic T-cell lymphoma (AITL). Methods: We studied the distribution of PD-1+ cells in reactive lymphadenopathies (LA), including HIV-associated and dermatopathic LA (n = 5, each), Castleman (n = 3), Kikuchi (n = 2) and Rosai-Dorfman diseases (n = 1), sarcoidoses (n = 7) and follicular hyperplasias (n = 8). Results: The highest concentrations of PD-1+ cells in GC were found in Castleman and Rosai-Dorfman diseases (mean 57 and 50% of total cells, respectively), and the lowest in HIV-associated LA (mean 6%). The highest proportions in paracortices were found in Castleman disease, and in HIV-associated and dermatopathic LA (mean 7, 3 and 2%, respectively). PD-1+ cells predominated in the pale zones of GC in follicular hyperplasia. In HIV-associated LA, PD-1+ cells showed marked marginalization in the GC. No paracortical PD-1+ cells were found in sarcoidoses and Rosai-Dorfman disease. Conclusions: The varying distribution of PD-1+ cells in defined LA might indicate a functional relevance of these cells in the respective entities. Since increased numbers of PD-1+ cells outside GC are observed in various LA, this finding might not be entirely specific for pattern I AITL.
Family Participation Can Improve Unilateral Spatial Neglect in Patients with Acute Right Hemispheric Stroke
Authors: Osawa A. , Maeshima S.
Published: March 2010

Objective: Unilateral spatial neglect (USN) is one of the major behavioral disturbances in patients with cerebral lesions and often impairs the patients’ independence in activities of daily living (ADL). Although many studies have addressed the mechanism and assessment of USN, there have been only few reports on rehabilitation strategies for patients with USN. The present study examined whether family participation can contribute to an improvement in USN following an acute stroke. Design: This study compared the improvement at 3 weeks among patients treated with conventional exercise sessions and a program including the participation of family members. The study followed 34 stroke patients with hemiparesis and USN. Twenty had family participation in their therapy. The severity of USN was measured using the Behavioral Inattention Test (BIT) and a laterality index (LI). Mobility was assessed using the Rivermead Mobility Index (RMI), and ADL were assessed using the Barthel index. Results: The results showed a relationship between BIT score improvement and family participation, and the BIT score improvement reflected the LI improvement. The RMI and BIT scores showed that ADL improved more with than without family participation. Conclusion: Family participation improved not only the mobility but also USN, suggesting that it can make important contributions to acute stroke rehabilitation.
Hostility May Explain the Association between Depressive Mood and Mortality: Evidence from the French GAZEL Cohort Study
Authors: Lemogne Cédric , Nabi Hermann , Zins Marie , Cordier Sylvaine , Ducimetière Pierre , Goldberg Marcel , Consoli Silla M.
Published: March 2010

Background: Depressive mood is associated with mortality. Because personality has been found to be associated with depression and mortality as well, we aimed to test whether depressive mood could predict mortality when adjusting for several measures of personality. Methods: 20,625 employees of the French national gas and electricity companies gave consent to enter in the GAZEL cohort in 1989. Questionnaires were mailed in 1993 to assess depressive mood, type A behavior pattern, hostility, and the six personality types proposed by Grossarth-Maticek and Eysenck. Vital status and date of death were obtained annually for all participants. The association between psychological variables and mortality was measured by the Relative Index of Inequality (RII) computed through Cox regression. Results: 14,356 members of the GAZEL cohort (10,916 men, mean age: 49 years; 3,965 women, mean age: 46 years) completed the depressive mood scale and at least one personality scale. During a mean follow-up of 14.8 years, 687 participants had died. Depressive mood predicted mortality, even after adjustment for age, sex, education level, body mass index, alcohol consumption, and smoking [RII (95% CI) = 1.56 (1.16–2.11)]. However, this association was dramatically reduced (RII reduction: 78.9%) after further adjustment for cognitive hostility (i.e. hostile thoughts) [RII (95% CI) = 1.12 (0.80–1.57)]. Cognitive hostility was the only personality measure remaining associated with mortality after adjustment for depressive mood [RII (95% CI) = 1.97 (1.39–2.77)]. Conclusions: Cognitive hostility may either confound or mediate the association between depressive mood and mortality.
No Calcium-Fluoride-Like Deposits Detected in Plaque Shortly after a Sodium Fluoride Mouthrinse
Authors: Vogel G.L. , Tenuta L.M.A. , Schumacher G.E. , Chow L.C.
Published: March 2010

Plaque ‘calcium-fluoride-like’ (CaF2-like) and fluoride deposits held by biological/bacterial calcium fluoride (Ca-F) bonds appear to be the source of cariostatic concentrations of fluoride in plaque fluid. The aim of this study was to quantify the amounts of plaque fluoride held in these reservoirs after a sodium fluoride rinse. 30 and 60 min after a 228 µg/g fluoride rinse, plaque samples were collected from 11 volunteers. Each sample was homogenized, split into 2 aliquots (aliquots 1 and 2), centrifuged, and the recovered plaque fluid combined and analyzed using microelectrodes. The plaque mass from aliquot 1 was retained. The plaque mass from aliquot 2 was extracted several times with a solution having the same fluoride, calcium and pH as the plaque fluid in order to extract the plaque CaF2-like deposits. The total fluoride in both aliquots was then determined. In a second experiment, the extraction completeness was examined by applying the above procedure to in vitro precipitates containing known amounts of CaF2-like deposits. Nearly identical fluoride concentrations were found in both plaque aliquots. The extraction of the CaF2-like precipitates formed in vitro removed more than 80% of these deposits. The results suggest that either CaF2-like deposits were not formed in plaque or, if these deposits had been formed, they were rapidly lost. The inability to form persistent amounts of CaF2-like deposits in plaque may account for the relatively rapid loss of plaque fluid fluoride after the use of conventional fluoride dentifrices or rinses.
Correlation between Disc Damage Likelihood Scale and Optical Coherence Tomography in the Diagnosis of Glaucoma
Authors: Abdul Majid Aman Shah B. , Kwag Jee Hyun , Jung Sang Hoon , Yim Hye Bin , Kim Yeon Deok , Kang Kui Dong
Published: March 2010

Purpose: To investigate the relationship between the Disc Damage Likelihood Scale (DDLS), visual field and various optical coherence tomography (OCT) parameters for glaucoma diagnosis. Methods: The study comprised 149 eyes from 149 patients. The patients were categorized as normal, glaucoma suspect or with glaucoma. They were clinically examined and graded according to the DDLS system. OCT was performed to acquire both a retinal nerve fibre layer analysis and an optic nerve head analysis. The relationships between DDLS score, visual field and OCT parameters were analysed using multiple correlation analysis. Results: The normal, glaucoma suspect and glaucoma groups had average DDLS scores of 1.58 ± 1.40, 2.55 ± 1.93 and 5.33 ± 1.39, respectively. Evaluating the area under the receiver operator characteristic curve, the DDLS had the best predictive power (0.917), followed by corrected pattern standard deviation. Conclusion: The DDLS is a useful parameter in the diagnosis of glaucoma and it showed a close correlation with visual field, cup/disc ratio and OCT parameters.
Effect of Extracellular ATP on Cisplatin-Induced Cytotoxicity in Human Ovarian Carcinoma Cells
Authors: Rotte Anand , Garmann Dirk , Buβ Irina , Jaehde Ulrich
Published: March 2010

Background: Cisplatin resistance has been mainly associated with decreased cellular accumulation and increased intracellular glutathione (GSH) levels. ATP is known to increase the membrane permeability of cells and to decrease intracellular GSH levels. Our study aimed at using extracellular ATP to sensitize ovarian carcinoma cells towards cisplatin. Methods: The MTT assay was used to determine the EC50 of cisplatin in the human ovarian carcinoma cell line A2780 and its cisplatin-resistant variant A2780cis. Intracellular platinum concentrations were determined using flameless atomic absorption spectrometry. Results: Preincubation and concomitant incubation with ATP did not alter the EC50 of cisplatin. The presence of 100 µM ATP along with cisplatin decreased cell survival in A2780 but not in A2780cis cells. Extracellular ATP did not increase the cellular accumulation of cisplatin in both A2780 and A2780cis cells. Conclusion: The presence of extracellular ATP during treatment with cisplatin leads to additive cytotoxicity in the sensitive A2780 but not in cisplatin-resistant A2780cis cells.
Gene Expression Profile of Colon Cancer Cell Lines Treated with SN-38
Authors: Wallin Å. , Francis P. , Nilbert M. , Svanvik J. , Sun X.-F.
Published: March 2010

Aim: Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1 inhibitor irinotecan which leads to cell cycle arrest and apoptosis. Material and Methods: The study included 3 colon cancer cell lines: KM12C, KM12SM and KM12l4a. The 3 cell lines were treated with SN-38, and samples were obtained after 24 and 48 hour treatments. The gene expression analyses were performed using oligonucleotide microarrays comprising of ∼27,000 spots where the untreated controls were compared to the SN-38-treated samples. Results: Unsupervised clustering clearly distinguished the treated cell lines from the untreated. Supervised analysis identified 3,974 significant genes (p = 0.05) differentiating the treated samples from the untreated, majority of which were down-regulated after treatment. The top-ranked down-regulated genes in the treated cell lines included those related to receptor and kinase activity, signal transduction, apoptosis, RNA processing, protein metabolism and transport, cell cycle and transcription. A smaller number of genes were up-regulated in the cell lines after treatment and included genes involved in apoptosis, transcription, development and differentiation. Conclusions: These results demonstrate that the expression of the genes involved in cell proliferation and apoptosis as well as RNA, DNA and protein metabolism were affected by SN-38. The impact of certain genes on colorectal cancer development needs to be further evaluated; however, these results could serve as a basis for further studies in order to find targets for irinotecan treatment.
Characterization of cycP Gene Expression in Achromobacter xylosoxidans NCIMB 11015 and High-Level Heterologous Synthesis of Cytochrome c′ in Escherichia coli
Authors: Harris Roger L. , Barbieri Sonia , Paraskevopoulos Kostas , Murphy Loretta M. , Eady Robert R. , Hasnain S. Samar , Sawers R. Gary
Published: March 2010

The cycP gene encoding a periplasmic cytochrome c′ from the denitrifying β-proteobacterium Achromobacter xylosoxidans was characterized. The genes flanking cycP encode components of a mobile genetic element characteristic of the β-proteobacteria, suggesting that cycP has inserted within a transposon or insertion element. The gene therefore does not form part of a denitrification operon or gene cluster. The level of expression of the cycP gene and the level of synthesis of its corresponding gene product were found to increase by maximally 3-fold anaerobically. Expression of cycP appears to occur mainly by non-specific read-through transcription from portions of the insertion element. Conditions were developed for high-level overproduction of cytochrome c′ in Escherichia coli, which resulted in signal peptide cleavage concomitant with secretion of the protein into the periplasm. Using a single-step purification, 20–30 mg of pure protein were isolated from a 1-litre culture. Based on UV-visible spectrophotometry the dimeric protein was shown to have a full complement of haem and to be indistinguishable from the native protein purified from A. xylosoxidans. This system provides an excellent platform to facilitate biochemical and structural dissection of the mechanism underlying the novel specificity of NO binding to the proximal face of the haem.
Dual Role of Interleukin-1α in Delayed-Type Hypersensitivity and Airway Hyperresponsiveness
Authors: Caucig Peri , Teschner Daniel , Dinges Stephanie , Maxeiner Joachim H. , Reuter Sebastian , Finotto Susetta , Taube Christian , von Stebut Esther
Published: March 2010

Background: Using a T helper (Th)1/Th2 disease model, we previously showed that genetically determined Th development depends on dendritic cell-derived interleukin (IL)-1α. In Leishmania major infections, Th1 immunity develops if IL-1α is present during T cell priming, whereas at later time points, IL-1α worsens disease outcome. In the present study, we determined the role of IL-1α in other Th2-mediated diseases. Methods: BALB/c mice were subjected to delayed-type hypersensitivity (DTH) or ovalbumin (OVA)/alum-induced allergic asthma in the presence or absence of IL-1α. Results: In DTH, mice treated with IL-1α during sensitization with keyhole limpet hemocyanin (KLH)/alum developed decreased footpad swelling associated with elevated KLH-specific interferon-γ levels. In asthma, significantly decreased airway hypersensitivity responses (AHRs) were detected upon treatment with IL-1α during T cell priming. In contrast to control mice, IL-1α-treated mice showed reduced peribronchial inflammatory infiltrates. The bronchoalveolar lavage (BAL) fluid contained significantly decreased eosinophil numbers (approximately 50%), but 4 times more neutrophils. The BAL fluid of IL-1α-treated BALB/c exhibited reduced amounts of IL-5 and OVA-specific IgE serum levels. In contrast, IL-1α treatment at later time points after sensitization or during allergen challenge worsened AHR, had no effect on lung inflammation and BAL fluid cell composition. Furthermore, cytokine levels (IL-5, IL-13) and antigen-specific IgE were increased or unaltered under these conditions. Conclusion: Similarly to leishmaniasis, IL-1α administration during sensitization of Th2-mediated allergic reactions suppresses the course of disease by shifting the immune response towards Th1, whereas later treatments worsen disease outcome. Future studies will elucidate the therapeutic value of IL-1α in asthmatic patients.
β2-Adrenoceptor Agonists Enhance Cytokine-Induced Release of Thymic Stromal Lymphopoietin by Lung Tissue Cells
Authors: Futamura Kyoko , Orihara Kanami , Hashimoto Noriko , Morita Hideaki , Fukuda Shuhei , Sagara Hironori , Matsumoto Kenji , Tomita Yasushi , Saito Hirohisa , Matsuda Akio
Published: March 2010

Background: Whileβ2-adrenoceptor agonists (β2-agonists) are widely used as bronchodilators in the treatment of asthma, there has been increasing concern that regular use of β2-agonists may adversely affect the control of asthma. However, the molecular mechanisms of such undesirable effects of β2-agonists are not fully understood. In this study, we examined the effects of β2-agonists on cytokine-induced production of thymic stromal lymphopoietin (TSLP), an indispensable cytokine in the development of allergic diseases, by lung tissue cells. Methods: Normal human bronchial epithelial cells (NHBE), smooth muscle cells (BSMC) and fibroblasts (NHLF) were stimulated with the IL-4 and TNF-α cytokines, alone and in combination, and their production of TSLP was examined by ELISA. The effects of β2-agonists (salmeterol, formoterol, salbutamol), intracellular cyclic adenosine monophosphate (cAMP)-elevating agents (8-bromo-cAMP, dibutyryl cAMP, forskolin) and a corticosteroid (fluticasone) on the cytokine-induced TSLP production were examined. Results: The following results were observed in all three types of lung tissue cells tested (that is, NHBE, BSMC and NHLF). Costimulation with IL-4 and TNF-α significantly induced TSLP production, and β2-agonists further enhanced it via upregulation of intracellular cAMP. However, addition of a corticosteroid to the cytokines and β2-agonist resulted in a marked decrease in TSLP production. Conclusions: β2-Agonists significantly enhanced the cytokine-induced TSLP production by primary human lung tissue cells. This may be partly responsible for the undesirable clinical effects of continuous β2-agonist monotherapy, and combination therapy with a corticosteroid might effectively inhibit TSLP-mediated allergic inflammation.
Development and Factorial Validation of a Short Version of the Narcissism Inventory (NI-20)
Authors: Daig I. , Burkert S. , Fischer H.F. , Kienast T. , Klapp B.F. , Fliege H.
Published: March 2010

Background: Narcissism is seen as a normal but heterogeneously formed personality variable, ranging from ‘grandiosity-exhibitionism’ to ‘vulnerability-sensitivity’. This article reports the development and factorial validation of a short version of a narcissism inventory. Sampling and Methods: The sample includes data of 4,509 consecutive psychosomatic inpatients. The overall sample was divided in 2 equally sized randomized subsamples. One sample (n = 2,262) was used for exploratory factor analysis (principal component analysis). The other sample (n = 2,265) was used for confirmatory tests of the model fit of the newly built NI-20 version, and to analyze the model fit separately for men and women using structural equation modeling with AMOS software. Results: The short version (NI-20) consists of 20 items, with items representing almost all of the original 18 subscales and 4 second-order dimensions. The NI-20 possesses properties similar to the NI-90, with a considerable gain in test economy. The 4-factor structure of the NI-20 was confirmed, and reaches good fit indices. Conclusions: The NI-20 is an economical instrument with acceptable psychometric characteristics that reflects the heterogeneous aspects of narcissism. A methodological limitation is that the interactions between sociodemographic variables were not included as potential predictors.
Gender Differences among Patients with a Single Depressive Episode
Authors: Bukh Jens D. , Bock Camilla , Vinberg Maj , Gether Ulrik , Kessing Lars Vedel
Published: March 2010

Background: Studies on gender differences in depression have usually included a mixture of patients with first-episode, chronic and recurrent depression. Consequently, the results might be confounded by the history of depression among participants. The present study evaluated gender differences in sociodemographic, clinical and treatment variables among patients suffering exclusively from single-episode depression. Method: Systematic recruitment of 301 participants via the Danish Psychiatric Central Research Register and assessment by means of questionnaires and interviews regarding psychiatric diagnoses, personality traits and disorders, stressful life events, family history, and treatment response. Results: Female patients showed a higher level of neuroticism and more residual anxiety symptoms after treatment of the depression. There were no gender differences in severity of depression, psychiatric co-morbidity (including personality disorders), stressful life events prior to onset, family loading of psychiatric disorders, or treatment outcome. Conclusion: The results provide evidence for a higher level of anxiety and neuroticism among females with a recent onset of depression, whereas other clinical characteristics of first-episode depression were equivalent between male and female patients. Only patients with contact to a psychiatric hospital were included; thus, the results cannot be generalized to patients in primary care.
Non-Invasive Measurement of Cardiac Output during Atrial Fibrillation: Comparison between Cardiac Magnetic Resonance Imaging and Inert Gas Rebreathing
Authors: Saur J. , Trinkmann F. , Doesch C. , Weissmann J. , Hamm K. , Schoenberg S.O. , Borggrefe M. , Haghi D. , Kaden J.J.
Published: March 2010

Objectives: Atrial fibrillation (AF) is one of the most frequent heart rhythm disorders. It potentially influences cardiac function and its measurement. Cardiac magnetic resonance imaging (CMR) has become the new gold standard for non-invasive assessment of cardiac output (CO). A novel inert gas rebreathing (IGR) device based on the Fick Principle also proved promising in patients in sinus rhythm (SR). The aim of our study was to compare the agreement of non-invasive CO measurements between CMR and IGR in AF patients. Methods: A total of 68 patients, 34 with AF and 34 pair-matched controls in SR, were included. Results: Bland-Altman analysis showed good agreement between both methods, with an average deviation of 0.2 ±1.2 l/min in the AF group versus 0.3 ±1.0 l/min in the SR group (p = 0.77). IGR demonstrated good agreement for CO between 2.0 and 5.4 l/min. However, in hyperdynamic circulatory conditions (CO >5.5 l/min), the increasing disagreement of IGR and CMR measurements reached statistical significance. Conclusions: Non-invasive CO measurements using CMR and IGR are feasible in patients suffering from AF. Good agreement was found between the two methods in an unselected cohort. Hyperdynamic circulatory conditions can lead to significant measurement differences which, however, do not affect the reproducibility of IGR.
Maternal Serum ADAM12 Levels Correlate with PAPP-A Levels during the First Trimester
Authors: Valinen Yrtti , Peuhkurinen Sini , Järvelä Ilkka Y. , Laitinen Päivi , Ryynanen Markku
Published: March 2010

Background: We wished to investigate the correlation between a new Down screening marker ADAM12 (a disintegrin and metalloproteinase-12) and pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (fβ-hCG) during the first trimester of pregnancy. Methods: ADAM12, PAPP-A and fβ-hCG were measured in 225 serum samples of randomly chosen pregnancies with completely normal outcome. The samples were taken between pregnancy weeks 9+0 and 12+6. Results: The ADAM12 levels tended to increase with advanced gestational age and the highest levels were detected at pregnancy week 12. The ADAM12 levels correlated with PAPP-A levels. After weight correction and logarithmic transformation the multiples of median (MoM) of ADAM12 still correlated with the MoMs of PAPP-A and also with the MoMs of fβ-hCG. Smokers had lower ADAM12 levels than non-smokers. Conclusion: The secretion of ADAM12 seems to resemble the secretion of PAPP-A in the end of the first trimester. Accordingly ADAM12 appears not to be a separate marker independent of PAPP-A. It remains to be assessed whether adding ADAM12 in Down screening risk calculation will reduce the false positive rate during the first trimester of pregnancy.
Fatty Acid-Bearing Albumin Induces VCAM-1 Expression through c-Src Kinase-AP-1/NF-ĸB Pathways: Effect of L-Carnitine
Authors: Baek Joo Eun , Yang Won Suk , Chang Jai Won , Kim Soon Bae , Park Su Kil , Park Jung Sik , Lee Sang Koo
Published: March 2010

Background: Fatty acid-bearing albumin [FA(+) albumin] exerts more deleterious effects in tubular cells than albumin alone. We investigated the effect of FA(+) albumin on the vascular cell adhesion molecule-1 (VCAM-1) expression and elucidated the underlying signaling pathways. We further examined the effect of L-carnitine, since it was known to modulate intracellular fatty acid concentration. Methods: Activation of AP-1 and NF-ĸB was assessed by electrophoretic mobility shift assay. Phosphorylation of protein kinase was examined by Western blot analysis. VCAM-1 mRNA and protein expression were measured by Northern blot analysis and cell ELISA. Results: FA(+) albumin induced VCAM-1 expression via activation of AP-1 and NF-ĸB, which was mediated through activation of c-Src kinase, followed by MAP kinases (p38, ERK 1/2, JNK-1) and IĸB kinase and IĸB-α, respectively. Inhibitors of protein kinase C and tyrosine kinase, anti-oxidants and intracellular calcium chelator suppressed the FA(+) albumin-induced activation of c-Src kinase. L-Carnitine suppressed the FA(+) albumin-induced VCAM-1 expression via inhibition of c-Src kinase. Conclusions: VCAM-1 expression with activation of c-Src kinase-AP-1/NFĸB pathways might be one of the possible mechanisms that linked FA(+) albumin to tubulointerstitial injury. L-Carnitine might be beneficial in attenuating FA(+) albumin-induced tubular injury.
A Simple Modification of the Separation Method Reduces Heterogeneity of Adipose-Derived Stem Cells
Authors: Griesche Nadine , Luttmann Werner , Luttmann Arlette , Stammermann Thekla , Geiger Helmut , Baer Patrick C.
Published: March 2010

High hopes are put into the use of mesenchymal stem cells (MSCs) in various approaches for tissue engineering and regenerative medicine. MSCs are derived from different tissues with only small differences in their phenotype or their differentiation potential, but higher differences in the cell yield. Since fat is easily accessible and contains a high amount of MSCs to be isolated, adipose-derived stem cells (ASCs) are very promising for clinical approaches. ASCs are not a completely homogeneous cell population. Our study was initiated to explore an easy and convenient method to reduce heterogeneity. We tested different isolation methods: (1) the standard isolation method for ASCs based on plastic attachment, (2) the standard method with an initial washing step after 60 min of adherence and (3) immunomagnetic isolation by 4 typical markers (CD49a, CD90, CD105 and CD271). Cells isolated by these methods were evaluated using quantitative PCR and flow cytometry as well as by their differentiation potential. Washing led to a significantly lower expression of desmin, smA and six2, and a higher expression of the stem cell markers nestin, oct-4 and sall-1, compared to standard isolated cells, while the immunomagnetically isolated cells showed no significant changes. All cells independent of the isolation method could be induced to differentiate into adipocytes and osteoblasts. Our study demonstrates that a simple washing step reduces heterogeneity of cultured ASCs according to PCR analysis, whereas the immunomagnetic isolation only showed minor advantages compared to the standard method, but the disadvantage of significantly lower cell yields in the primary isolates.
In vivo Detection of Vulnerable Atherosclerotic Plaque by MRI in a Rabbit Model
Authors: Phinikaridou Alkystis , Ruberg Frederick L. , Hallock Kevin J. , Qiao Ye , Hua Ning , Viereck Jason , Hamilton James A.
Published: March 2010

Background—

The ability to identify atherosclerotic plaques with a high risk for sudden disruption before stroke or myocardial infarction would be of great utility. We used a rabbit model of controlled atherothrombosis to test whether in vivo MRI can noninvasively distinguish between plaques that disrupt after pharmacological triggering (vulnerable) and those that do not (stable).

Methods and Results—

Atherosclerosis was induced in male New Zealand White (n=17) rabbits by cholesterol diet and endothelial denudation of the abdominal aorta. After baseline (pretrigger) MRI with and without gadolinium contrast, the rabbits underwent 2 pharmacological triggerings to induce atherothrombosis, followed by another MRI 48 hours later (post-triggering). Atherosclerosis was identified by the pretriggered images in all rabbits, and thrombosis was identified in 9 of 17 animals (53%) by post-trigger MRI. After the animals were euthanized, 95 plaques were analyzed; 28 (29.5%) had thrombi (vulnerable) and 67 did not (stable) (70.5%). Pretriggered MRI revealed comparable stenosis in stable and vulnerable plaques, but vulnerable plaques had a larger plaque area (4.8�1.6 versus 3.0�1.0 mm
2
;
P
=0.01), vessel area (9.2�3.0 versus. 15.8�4.9 mm
2
;
P
=0.01), and higher remodeling ratio (1.16�0.2 versus 0.93�0.2;
P
=0.01) compared with stable plaques. Furthermore, vulnerable plaques more frequently exhibited (1) positive remodeling (67.8% versus 22.3%;
P
=0.01), in which the plaque is hidden within the vessel wall instead of occluding the lumen; and (2) enhanced gadolinium uptake (78.6% versus 20.9%;
P
=0.01) associated with histological findings of neovascularization, inflammation, and tissue necrosis.

Conclusions—

We demonstrate that in vivo MRI at 3.0 T detects features of vulnerable plaques in an animal model of controlled atherothrombosis. These findings suggest that MRI may be used as a noninvasive modality for localization of plaques that are prone to disruption.
Thioredoxin-1 Gene Therapy Enhances Angiogenic Signaling and Reduces Ventricular Remodeling in Infarcted Myocardium of Diabetic Rats
Authors: Samuel Samson Mathews , Thirunavukkarasu Mahesh , Penumathsa Suresh Varma , Koneru Srikanth , Zhan Lijun , Maulik Gautam , Sudhakaran Perumana R. , Maulik Nilanjana
Published: March 2010

Background—

The present study evaluated the reversal of diabetes-mediated impairment of angiogenesis in a myocardial infarction model of type 1 diabetic rats by intramyocardial administration of an adenoviral vector encoding thioredoxin-1 (
Ad.Trx1
). Various studies have linked diabetes-mediated impairment of angiogenesis to dysfunctional antioxidant systems in which thioredoxin-1 plays a central role.

Methods and Results—

Ad.Trx1
was administered intramyocardially in nondiabetic and diabetic rats immediately after myocardial infarction.
Ad.LacZ
was similarly administered to the respective control groups. The hearts were excised for molecular and immunohistochemical analysis at predetermined time points. Myocardial function was measured by echocardiography 30 days after the intervention. The
Ad.Trx1
-administered group exhibited reduced fibrosis, oxidative stress, and cardiomyocyte and endothelial cell apoptosis compared with the diabetic myocardial infarction group, along with increased capillary and arteriolar density. Western blot and immunohistochemical analysis demonstrated myocardial overexpression of thioredoxin-1, heme oxygenase-1, vascular endothelial growth factor, and p38 mitogen-activated protein kinase-β, as well as decreased phosphorylated JNK and p38 mitogen-activated protein kinase-α, in the
Ad.Trx1
-treated diabetic group. Conversely, we observed a significant reduction in the expression of vascular endothelial growth factor in nondiabetic and diabetic animals treated with tin protoporphyrin (SnPP, a heme oxygenase-1 enzyme inhibitor), even after
Ad.Trx1
therapy. Echocardiographic analysis after 4 weeks of myocardial infarction revealed significant improvement in myocardial functional parameters such as ejection fraction, fractional shortening, and E/A ratio in the
Ad.Trx1
-administered group compared with the diabetic myocardial infarction group.

Conclusions—

This study demonstrates for the first time that impairment of angiogenesis and myocardial dysfunction can be regulated by
Ad.Trx1
gene therapy in streptozotocin-induced diabetic rats subjected to infarction.
Dietary Intervention to Reverse Carotid Atherosclerosis
Authors: Shai Iris , Spence J. David , Schwarzfuchs Dan , Henkin Yaakov , Parraga Grace , Rudich Assaf , Fenster Aaron , Mallett Christiane , Liel-Cohen Noah , Tirosh Amir , Bolotin Arkady , Thiery Joachim , Fiedler Georg Martin , Blüher Matthias , Stumvoll Michael , Stampfer Meir J.
Published: March 2010

Background—

It is currently unknown whether dietary weight loss interventions can induce regression of carotid atherosclerosis.

Methods and Results—

In a 2-year Dietary Intervention Randomized Controlled Trial–Carotid (DIRECT-Carotid) study, participants were randomized to low-fat, Mediterranean, or low-carbohydrate diets and were followed for changes in carotid artery intima-media thickness, measured with standard B-mode ultrasound, and carotid vessel wall volume (VWV), measured with carotid 3D ultrasound. Of 140 complete images of participants (aged 51 years; body mass index, 30 kg/m
2
; 88% men), higher baseline carotid VWV was associated with increased intima-media thickness, age, male sex, baseline weight, blood pressure, and insulin levels (
P
<0.05 for all). After 2 years of dietary intervention, we observed a significant 5% regression in mean carotid VWV (−58.1 mm
3;
95% confidence interval, −81.0 to −35.1 mm
3
;
P
<0.001), with no differences in the low-fat, Mediterranean, or low-carbohydrate groups (−60.69 mm
3
, −37.69 mm
3
, −84.33 mm
3
, respectively;
P
=0.28). Mean change in intima-media thickness was −1.1% (
P
=0.18). A reduction in the ratio of apolipoprotein B
100
to apolipoprotein A1 was observed in the low-carbohydrate compared with the low-fat group (
P
=0.001). Participants who exhibited carotid VWV regression (mean decrease, −128.0 mm
3
; 95% confidence interval, −148.1 to −107.9 mm
3
) compared with participants who exhibited progression (mean increase, +89.6 mm
3
; 95% confidence interval, +66.6 to +112.6 mm
3
) had achieved greater weight loss (−5.3 versus −3.2 kg;
P
=0.03), greater decreases in systolic blood pressure (−6.8 versus −1.1 mm Hg;
P
=0.009) and total homocysteine (−0.06 versus +1.44 μmol/L;
P
=0.04), and a higher increase of apolipoprotein A1 (+0.05 versus −0.00 g/L;
P
=0.06). In multivariate regression models, only the decrease in systolic blood pressure remained a significant independent modifiable predictor of subsequent greater regression in both carotid VWV (β=0.23;
P
=0.01) and intima-media thickness (β=0.28;
P
=0.008) levels.

Conclusions—

Two-year weight loss diets can induce a significant regression of measurable carotid VWV. The effect is similar in low-fat, Mediterranean, or low-carbohydrate strategies and appears to be mediated mainly by the weight loss–induced decline in blood pressure.

Clinical Trial Registration—

http://www.clinicaltrials.gov. Unique Identifier: NCT00160108.
Response to Ticagrelor in Clopidogrel Nonresponders and Responders and Effect of Switching Therapies
Authors: Gurbel Paul A. , Bliden Kevin P. , Butler Kathleen , Antonino Mark J. , Wei Cheryl , Teng Renli , Rasmussen Lars , Storey Robert F. , Nielsen Tonny , Eikelboom John W. , Sabe-Affaki Georges , Husted Steen , Kereiakes Dean J. , Henderson David , Patel Dharmendra V. , Tantry Udaya S.
Published: March 2010

Background—

The antiplatelet effects of the Platelet Inhibition and Patient Outcomes (PLATO) trial dose of ticagrelor in patients nonresponsive to clopidogrel and after they switch agents are unknown.

Methods and Results—

Patients with stable coronary artery disease on aspirin therapy received a 300-mg clopidogrel load; nonresponders were identified by light transmittance aggregometry. In a 2-way crossover design, nonresponders (n=41) and responders (n=57) randomly received clopidogrel (600 mg/75 mg once daily) or ticagrelor (180 mg/90 mg twice daily) for 14 days during period 1. In period 2, all nonresponders switched treatment; half of the responders continued the same treatment, whereas the others switched treatment. Inhibition of platelet aggregation was higher in nonresponders treated with ticagrelor compared with clopidogrel (
P
<0.05). Treatment with ticagrelor among nonresponders resulted in a >10%, >30%, and >50% decrease in platelet aggregation from baseline in 100%, 75%, and 13% of patients, respectively. Platelet aggregation fell from 59±9% to 35±11% in patients switched from clopidogrel to ticagrelor and increased from 36±14% to 56±9% in patients switched from ticagrelor to clopidogrel (
P
<0.0001 for both). Platelet reactivity was below the cut points previously associated with ischemic risk measured by light transmittance aggregometry, VerifyNow P2Y
12
assay, and vasodilator-stimulated phosphoprotein phosphorylation in 98% to 100% of patients after ticagrelor therapy versus 44% to 76% of patients after clopidogrel therapy.

Conclusions—

Ticagrelor therapy overcomes nonresponsiveness to clopidogrel, and its antiplatelet effect is the same in responders and nonresponders. Nearly all clopidogrel nonresponders and responders treated with ticagrelor will have platelet reactivity below the cut points associated with ischemic risk.

Clinical Trial Registration—

http://www.clinicaltrials.gov. Unique Identifier: NCT00642811.
The Politics of Inequality: Voter Mobilization and Left Parties in Advanced Industrial States
Authors: Pontusson Jonas , Rueda David
Published: March 2010

Why is it that some countries have witnessed significant increases in inequality since the 1960s while at the same time experiencing very little change in the way politics is conducted? And why is it that in other countries, where inequality has increased much less, the Left has become substantially more redistributive? The answer, the authors argue, has to do with the interaction between inequality and political mobilization of low-income voters. The authors make two points in this article. First, high levels of inequality move Left parties to the left. Second, although increasing inequality pushes the core constituencies of Left parties to the left, it also makes some individuals less likely to be involved in politics. The authors argue that Left parties will respond to an increase in inequality only when low-income voters are politically mobilized. They explore these claims through a comparative analysis of Left party programs in 10 Organisation for Economic Co-operation and Development countries over the period 1966 to 2002.
Something to Hide? Anonymity and Pseudonyms in the Colonial West African Press
Authors: Newell Stephanie
Published: March 2010

This article examines the wide range of anonymous and pseudonymous naming practices to be found in West African newspapers between the 1880s and 1930s, and asks about the shape of a West African history of anonymity as compared with recent histories of anonymity in European literature. The article also discusses the ways in which colonial West African uses of anonymity and pseudonyms challenge postcolonial scholarship on agency, subjectivity, resistance, authenticity and identity.
Can You Really See through a Squint? Theoretical Underpinnings in Ama Ata Aidoo’s Our Sister Killjoy
Authors: Sterling Cheryl
Published: March 2010

Ama Ata Aidoo’s Our Sister Killjoy is read as an inversion of the colonial travel narrative, addressing the continued asymmetrical power relations between Europe and Africa. The paper posits Sissie, its focal character, as a site of theoretical transformations, engaging with issues of racial subjectivity, sexuality and political positionality in relation to the neo-colonial African state. It further argues that Aidoo situates a performative self in the text through an interrogatory narrative voice that succeeds in both deforming the novelistic pattern and participating in the critique of Western subjectivity and hegemonic feminist positioning, while inserting a resistant feminist ideology into Pan-Africanist discourse to re-envision the role of African women in Africa’s development.
Embodiment and the Reconstruction of Gender Roles in Leow Puay Tin’s Family
Authors: Philip Susan
Published: March 2010

Through an analysis of both the text and performance of Malaysian playwright Leow Puay Tin’s Family, this paper looks at the construction of the family unit in a particular segment of Malaysian society, in order to examine the tension existing between socially and authoritatively imposed gender identities and individuals’ responses to these imposed identities. Individuals within Leow’s fictional family are embodied in specific ways which support and perpetuate patriarchal structures. However, this embodiment is revealed to be groundless and they are therefore forced to reconstitute imposed identities by imagining or living within their bodies differently. The analysis of these issues is enhanced through a study of the production of this play in Kuala Lumpur in 1998, which re-articulated Leow’s vision through unusual and confrontational staging, casting and costuming choices which were able to go further than the text in examining and physicalizing questions about the borders and limits of gender identity.
A Pastoral for Mr. Biswas
Authors: Hentea Marius
Published: March 2010

The opening chapter of V.S. Naipaul’s A House for Mr. Biswas is entitled “Pastoral”, but the word itself never appears in the novel. This is especially odd because all of the other chapter titles are grounded within the text as either geographic or temporal designations. “Pastoral” stands out for its absence, and this article reads A House for Mr. Biswas through the lens of the missing pastoral. While many works treat Naipaul’s use of landscape, this essay looks at the pastoral as a literary form and also, in Naipaul’s view, as a representative metaphor for the British literary tradition. While Biswas is saturated with pastoral imagery, the pastoral is impossible in the colonial society Naipaul depicts. It is only by escaping the temptations of the pastoral, both for Mr. Biswas and also for Naipaul, that meaningful experience can be achieved.
Gender and Attitudes Toward People Using Wheelchairs: A Multidimensional Perspective
Authors: Vilchinsky Noa , Werner Shirli , Findler Liora
Published: March 2010

This study aims to investigate the effect of observer’s gender and target’s gender on attitudes toward people who use wheelchairs due to a physical disability. Four hundred four Jewish Israeli students without disabilities completed the Multidimensional Attitudes Scale Toward Persons With Disabilities (MAS). Initially, confirmatory factor analysis was used to revalidate the MAS. Five factors of attitudes were confirmed: distancing behaviors, positive cognitions, negative emotions, interpersonal stress, and calm. Findings showed that an encounter with a person using a wheelchair raised more positive cognitions and less distancing behaviors, but also evoked more negative emotions, than an encounter with a person without a disability. In the case of an encounter with a person without a disability, men contributed to greater interpersonal stress among women, whereas women contributed to greater interpersonal stress among men. The multidimensional approach revealed that the effect of gender was mostly salient with regard to interpersonal stress.
New Frontiers of the Reputation—Performance Relationship: Insights From Multiple Theories
Authors: Bergh Donald D. , Ketchen David J. , Boyd Brian K. , Bergh Julianne
Published: March 2010

Understanding the influences on organizational performance is a key goal of the strategic management field. A prior study (Rindova, Williamson, Petkova, & Sever, 2005) offered significant progress toward this goal in the context of the concept of reputation through the application of multiple theories and alternate empirical tests. In a subsequent article (Boyd, Bergh, & Ketchen, 2010), the authors sought to extend that knowledge via the application of a third theoretical perspective and additional analyses. In this reply, the authors extend on the comments made by Rindova, Williamson, and Petkova (2010) and offer additional theoretical insights on reputation, leveraging ideas from the resource-based view, transaction cost economics, signaling theory, and social status research. The authors also attempt to lay a foundation for future inquiry by using those theories to identify a series of research questions.