bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of the Tumor Microvasculature by Phosphoinositide-3 Kinase Inhibition Increases Doxorubicin Delivery In Vivo
Authors: Qayum Naseer , Im Jaehong , Stratford Michael R. , Bernhard Eric J. , McKenna W. Gillies , Muschel Ruth J.
Published: November 2011

Purpose: Because effective drug delivery is often limited by inadequate vasculature within the tumor, the ability to modulate the tumor microenvironment is one strategy that may achieve better drug distribution. We have previously shown that treatment of mice bearing tumors with phosphoinositide-3 kinase (PI3K) inhibitors alters vascular structure in a manner analogous to vascular normalization and results in increased perfusion of the tumor. On the basis of that result, we asked whether inhibition of PI3K would improve chemotherapy delivery.

Experimental Design: Mice with xenografts using the cell line SQ20B bearing a hypoxia marker or MMTV-neu transgenic mice with spontaneous breast tumors were treated with the class I PI3K inhibitor GDC-0941. The tumor vasculature was evaluated by Doppler ultrasound, and histology. The delivery of doxorubicin was assessed using whole animal fluorescence, distribution on histologic sections, high-performance liquid chromatography on tumor lysates, and tumor growth delay.

Results: Treatment with GDC-0941 led to approximately three-fold increases in perfusion, substantially reduced hypoxia and vascular normalization by histology. Significantly increased amounts of doxorubicin were delivered to the tumors correlating with synergistic tumor growth delay. The GDC-0941 itself had no effect on tumor growth.

Conclusion: Inhibition of PI3K led to vascular normalization and improved delivery of a chemotherapeutic agent. This study highlights the importance of the microvascular effects of some novel oncogenic signaling inhibitors and the need to take those changes into account in the design of clinical trials many of which use combinations of chemotherapeutic agents. Clin Cancer Res; 18(1); 161–9. ©2011 AACR.
Inhibition of p38 MAPK-Dependent Excision Repair Cross-Complementing 1 Expression Decreases the DNA Repair Capacity to Sensitize Lung Cancer Cells to Etoposide
Authors: Tsai Min-Shao , Weng Shao-Hsing , Chen Huang-Jen , Chiu Yu-Fan , Huang Yu-Ching , Tseng Sheng-Chieh , Kuo Ya-Hsun , Lin Yun-Wei
Published: November 2011

Etoposide (VP-16), a topoisomerase II inhibitor, is an effective anticancer drug currently used for the treatment of a wide range of cancers. Excision repair cross-complementary 1 (ERCC1) is a key protein involved in the process of nucleotide excision repair. High level of ERCC1 expression in cancers is associated with resistance to DNA damage-based chemotherapy. In this study, the effects of p38 mitogen-activated protein kinase (MAPK) signal on the ERCC1 expression induced by etoposide in non–small cell lung cancer (NSCLC) cell lines was investigated. Etoposide increased phosphorylated MAPK kinase 3/6 (MKK3/6)-p38 MAPK and ERCC1 protein and mRNA levels in A549 and H1975 cells. Moreover, SB202190, a p38 inhibitor, or knockdown of p38 expression by specific short interfering RNA (siRNA) significantly decreased the etoposide-induced ERCC1 protein levels and DNA repair capacity in etoposide-exposed NSCLC cells. Enhancement of p38 activation by constitutively active MKK6 (MKK6E) increased ERCC1 protein levels. Specific inhibition of ERCC1 by siRNA significantly enhanced the etoposide-induced cytotoxicity and hypoxanthine guanine phosphoribosyltransferase (hprt) gene mutation rate. Moreover, the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) could decrease the etoposide-induced p38 MAPK-mediated ERCC1 expression and augment the cytotoxic effect and growth inhibition by etopsoside. 17-AAG and etoposide-induced synergistic cytotoxic effect and DNA repair capacity decrease could be abrogated in lung cancer cells with MKK6E or HA-p38 MAPK expression vector transfection. Our results suggest that in human NSCLC cells, ERCC1 is induced by etoposide through the p38 MAPK pathway, and this phenomenon is required for NSCLC survival and resistant DNA damage. Mol Cancer Ther; 11(3); 561–71. ©2011 AACR.
A Novel Platform for Detection of CK+ and CK− CTCs
Authors: Pecot Chad V. , Bischoff Farideh Z. , Mayer Julie Ann , Wong Karina L. , Pham Tam , Bottsford-Miller Justin , Stone Rebecca L. , Lin Yvonne G. , Jaladurgam Padmavathi , Roh Ju Won , Goodman Blake W. , Merritt William M. , Pircher Tony J. , Mikolajczyk Stephen D. , Nick Alpa M. , Celestino Joseph , Eng Cathy , Ellis Lee M. , Deavers Michael T. , Sood Anil K.
Published: November 2011

Metastasis is a complex, multistep process that begins with the epithelial–mesenchymal transition (EMT). Circulating tumor cells (CTC) are believed to have undergone EMT and thus lack or express low levels of epithelial markers commonly used for enrichment and/or detection of such cells. However, most current CTC detection methods target only EpCAM and/or cytokeratin (CK) to enrich epithelial CTCs, resulting in failure to recognize other, perhaps more important, CTC phenotypes that lack expression of these markers. Here, we describe a population of complex aneuploid CTCs that do not express CK or CD45 antigen in patients with breast, ovarian, or colorectal cancer. These cells were not observed in healthy subjects. We show that the primary epithelial tumors were characterized by similar complex aneuploidy, indicating conversion to an EMT phenotype in the captured cells. Collectively, our study provides a new method for highly efficient capture of previously unrecognized populations of CTCs.

Significance: Current assays for CTC capture likely miss populations of cells that have undergone EMT. Capture and study of CTCs that have undergone EMT would allow a better understanding of the mechanisms driving metastasis. Cancer Discovery; 1(7); 580–86. ©2011 AACR.

This article is highlighted in the In This Issue feature, p. 539
Polymorphisms of Hepatitis C Virus Non-Structural Protein 5A and Core Protein and Clinical Outcome of Pegylated-Interferon/Ribavirin Combination Therapy
Authors: El-Shamy Ahmed , Kim Soo-Ryang , Ide Yoshi-Hiro , Sasase Noriko , Imoto Susumu , Deng Lin , Shoji Ikuo , Hotta Hak
Published: November 2011

Objective: Hepatitis C virus (HCV genome) polymorphisms are thought to influence the outcome of pegylated-interferon/ribavirin (PEG-IFN/RBV) therapy. This study aimed to examine non-structural protein 5A (NS5A) polymorphisms, e.g. IFN/RBV resistance-determining region (IRRDR) and IFN sensitivity-determining region (ISDR), and core protein polymorphism as predictive therapeutic markers. Methods: Pretreatment sequences of NS5A and core regions were analyzed in 68 HCV-1b-infected patients treated with PEG-IFN/RBV. Results: Of 24 patients infected withHCV having an IRRDR with 6 or more mutations (IRRDR≧6), 18 (75%) patients achieved sustained virological response (SVR), whereas only 11 (25%) of 44 patients infected with HCV having IRRDR≤5 did. IRRDR≧6 was significantly associated with SVR (p < 0.0001). On the other hand, ISDR≧2 was significantly associated with relapse (either before [breakthrough] or after end-of-treatment response [ETR[-]relapse]) (p < 0.05) and a point mutation of the core protein from Arg to Gln at position 70 (Gln70) was significantly associated with null-response (p < 0.05). Multivariate analysis identified IRRDR≧6 as the only viral genetic factor that independently predicted SVR. Conclusion: NS5A (IRRDR and ISDR) and core protein polymorphisms are associated with the outcome of PEG-IFN/RBV therapy for chronic hepatitis C. In particular, IRRDR≧6 is a useful marker for prediction of SVR.
Development of an Indirect ELISA with Artificially Synthesized N Protein of PPR Virus
Authors: Zhang Guo-rui , Zeng Jiang-yong , Zhu Yu-min , Dong Shi-juan , Zhu Se , Yu Rui-song , Duoji Ciren , Lei Zhi-hai , Li Zhen
Published: November 2011

The full-length gene encoding the nucleocapsid (N) protein of the virus (PPRV) responsible for an outbreak of peste des petits ruminants in Tibet in 2007 was synthesized in two stages using overlapping PCR without the need for viral genomic cDNA as template. The full-length N gene was successfully expressed in Escherichia coli, and the purified gene product bound to monoclonal antibody raised against PPRV N protein. Furthermore, it was able to replace recombinant B-N antigen as the coating antigen in a commercial ELISA kit prepared with another PPRV strain. Recombinant protein was employed as the coating antigen to develop an indirect ELISA for PPRV antibody detection in the sera of infected small ruminants. Antibody detection was optimal at a 1:200 serum dilution and an antigen concentration of 3.2 µg/ml, and the positive threshold (cutoff) value of the assay was 2.18. Analysis of 697 serum samples revealed the sensitivity and specificity of the indirect ELISA to be 96.7 and 96.1%, respectively, compared with a commercially available ELISA test.
Comparative Proteome Analysis of Silkworm in Its Susceptibility and Resistance Responses to Bombyx mori Densonucleosis Virus
Authors: Chen Hui-qing , Yao Qin , Bao Fang , Chen Ke-ping , Liu Xiao-yong , Li Jun , Wang Lin
Published: November 2011

Bombyx mori densonucleosis virus (BmDNV) is one of the most disastrous viruses in cocoon production. Silkworm resistance to BmDNV has been examined previously using a number of traditional biochemical and molecular techniques. In this study, a near isogenic line, BC6, was constructed to eliminate the difference in inherited background, which has 99.9% identity with the susceptible strain but carries a resistant gene. We utilized a proteomic approach involving two-dimensional differential gel electrophoresis and mass spectrometry to examine changes in the midgut proteins from the susceptible and resistant silkworm larvae infected with BmDNV. The protein profiles were compared and 9 differentially expressed proteins were identified by mass spectrometry. In the resistant strains, the heat-shock 70-kDa protein cognate, cytochrome P450, vacuolar ATP synthase subunit B, arginine kinase, vacuolar ATP synthase subunit D and glutathione S-transferase sigma were strongly upregulated and α-tubulin was downregulated. Our results imply that these upregulated genes and the downregulated genes might be involved in B. mori immune responses against BmDNV-Z infection.
Expression of DcR3 and Its Effects in Kaposi’s Sarcoma-Associated Herpesvirus-Infected Human Endothelial Cells
Authors: Yoo Seungmin , Jang Jaehyuk , Kim Sil , Cho Haewol , Lee Myung-Shin
Published: November 2011

Objective: Kaposi’s sarcoma-associated herpesvirus (KSHV) is classified as a gamma-herpesvirus and it causes Kaposi’s sarcoma in patients infected with the human immunodeficiency virus (HIV). Decoy receptor 3 (DcR3) is known as a decoy receptor for Fas ligand, LIGHT and TL1A and it can neutralize the biological effect of TL1A by inhibiting the TL1A-DR3 interaction in human endothelial cells. The present study examined the expression of DcR3 in human endothelial cells and its effect during the early stages of KSHV infection. Methods: The expression of DcR3 was assessed using real-time RT-PCR and ELISA in human umbilical cord vein endothelial cells (HUVECs) infected with KSHV. Cell proliferation and apoptosis of KSHV-infected HUVECs were assessed after treatment of infected cells with an anti-DcR3 antibody or recombinant human TL1A. Results: DcR3 expression was induced during the early phase of KSHV infection. Inhibition of DcR3 with anti-DcR3 antibodies or recombinant human TL1A-induced apoptosis in KSHV-infected HUVECs. Conclusion: The expression of DcR3 plays an important role in the prevention of apoptosis in HUVECs during the early phases of KSHV infection, thus ensuring the successful establishment and maintenance of the viral infection.
Characterization of Hepatitis B Virus Molecular Genotypes in Chongqing and Quantitative Serological Markers in Patients during Natural Phases of Chronic Hepatitis B Infection
Authors: Xiang Yu , Huang Shifeng , Xia Jirong , Ye Diqing , Chen Pu , Zhang Liping
Published: November 2011

Background/Aims: The present study was launched to systematically characterize the molecular genotypes and quantitative serological biomarkers during the natural course of chronic hepatitis B (CHB) infection in a patient population from Chongqing, China. Methods: A total of 140 patients were enrolled and grouped according to the natural phases of HBV infection: HBeAg (+) immune tolerance, immune clearance, HBeAg (–) low replicative and reactivation phase. Nested PCR was used for HBV molecular genotyping and chemiluminescent microparticle immunoassay for quantitative serological detection. Results: Subgenotypes B2 and C2 were found to be most prevalent with genotype B patients showing more potent viral activity. HBsAg level was found to be significantly correlated with HBV DNA, HBeAg, age, ALT and AST levels during some phases of CHB. Conclusion: These results indicated that molecular genotyping and quantitative serological detection might be helpful for earlier prediction of the long-term disease outcomes.
Neuroimmunoendocrine Interactions in Patients with Recurrent Major Depression, Increased Early Life Stress and Long-Standing Posttraumatic Stress Disorder Symptoms
Authors: Lopes Rodrigo Pestana , Grassi-Oliveira Rodrigo , de Almeida Lettícia R. , Stein Lilian Milnitsky , Luz Clarice , Teixeira Antonio L. , Bauer Moisés E.
Published: November 2011

Background: Traumatic events experienced in childhood may lead to psychiatric diseases in adult life, including major depressive disorder (MDD). It remains obscure to what extent early life stress (ELS) is associated with biologically relevant changes in MDD. Objective: We investigated both neuroendocrine and immunological correlates in recurrent MDD with ELS and current posttraumatic stress disorder symptoms. Methods: Thirty-eight female MDD patients with or without childhood trauma and 15 healthy controls took part in this study. Salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed by radioimmunoassays. Peripheral blood mononuclear cells (PBMCs) were isolated and T cell proliferation and cellular sensitivity to steroids and DHEAS were evaluated by colorimetric assays. Th1/Th2 cytokines were assessed by cytometric bead arrays. Results: MDD patients with or without previous trauma had similarly lower salivary cortisol and DHEAS in parallel with blunted T cell proliferation. PBMCs of depressives were significantly less sensitive to dexamethasone or epinephrine than those of the controls. PBMCs of MDD patients produced significantly lower interleukin (IL)-2, IL-4 and tumor necrosis factor-α levels when compared to healthy controls. Conclusion: We found that a history of ELS did not modify the blunted neuroendocrine and immunological alterations presented by recurrent depressed patients.
Dendritic Cells in Experimental Renal Inflammation – Part I
Authors: Lindenmeyer Maja , Noessner Elfriede , Nelson Peter J. , Segerer Stephan
Published: November 2011

Dendritic cells (DCs) are bone marrow-derived professional antigen-presenting cells that act as master regulators of acquired and innate immune responses. While descriptions of cells with dendritic morphology in rodent kidneys date back to the early 1970s, a network of DCs in the mouse kidney has only recently been described. DCs acquire distinct phenotypic and functional characteristics depending on the microenvironment and the disease stages. Concomitantly, their communication with cells of the adaptive immunity might have tissue-protective or tissue-deleterious consequences. This review summarizes results from recent studies on the role of DCs in experimental renal inflammation.
Dendritic Cells in Human Renal Inflammation – Part II
Authors: Noessner Elfriede , Lindenmeyer Maja , Nelson Peter J. , Segerer Stephan
Published: November 2011

Dendritic cells (DCs) are bone marrow-derived professional antigen-presenting cells that act as master regulators of acquired and innate immune responses. Here, we review the available information on their role in human renal inflammation. In the 1980s and early 1990s, major histocompatibility complex class II antigen- (HLA-DR) positive DCs were first described in normal human kidneys and in the interstitium of kidneys from patients with glomerulonephritis. Several DC subtypes were subsequently distinguished based on their expression of CD1c/BDCA-1, CD141/BDCA-3 and CD209/DC-SIGN (in combination with HLA-DR). These cells were almost exclusively found in the tubulointerstitium, with increased numbers seen during glomerulonephritis. It appears that the human renal tubulointerstitium harbors different DC types which allow the collection of both exogenous as well as endogenous antigens. Plasmacytoid DCs have a plasma cell-like morphology and were commonly found within nodular tubulointerstitial infiltrates. Follicular DCs are rarely seen, but show a predominant localization in organized infiltrates. CD207/langerin is a marker for Langerhans cells. Langerin-positive cells have been found in association with the collecting ducts and urothelium. A functional characterization of these subtypes has been hampered by the difficulty of obtaining samples for analysis. However, these studies are clearly required to define the role of DCs and DC subsets in the pathophysiology of renal disease.
Mannitol Reduces the Hydrostatic Pressure in the Proximal Tubule of the Isolated Blood-Perfused Rabbit Kidney during Hypoxic Stress and Improves Its Function
Authors: Bipat Robbert , Steels Paul , Cuypers Yves , Toelsie Jerry R.
Published: November 2011

Background/Aims: Hypoxia may play a role in the development of renal failure in donated kidneys. In the present study, the effects of hypoxia on isolated blood-perfused rabbit kidneys were investigated and the effects of mannitol were explored, giving special attention to intratubular pressure. Methods: Kidneys were perfused with their autologous blood during four 30-min periods (P1–P4). P1 was considered baseline function. In P2, hypoxia was induced either alone or with an infusion of mannitol (15 mg/min) during P2–P4. Reoxygenation was applied after P2. Proximal intratubular pressure was measured in all conditions. Results: During hypoxia, renal blood flow doubled and restored immediately in P3. Urine flow stopped in P2, except in the series with mannitol, but gradually resumed in P3 and P4. Likewise, creatinine clearance recovered slightly (<25%) in P4, except for the series with mannitol, where it still could be measured in P2 and reached a value >50% of P1. Proximal intratubular pressure (mean ± SD) increased from 12 ± 5 in P1 to 24 ± 11 mm Hg during hypoxia and returned to 10 ± 6 mm Hg in P3. This increase was not observed with mannitol. Conclusion: Cellular swelling might be responsible for the suppressed filtration during hypoxia and can be prevented by mannitol.
Renal Involvement in Psychological Eating Disorders
Authors: Li Cavoli Gioacchino , Mulè Giuseppe , Rotolo Ugo
Published: November 2011

Psychological eating disorders – anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder – are an increasing public health problem with severe clinical manifestations: hypothermia, hypotension, electrolyte imbalance, endocrine disorders and kidney failure; they are of interest to nephrologists, but pathophysiological mechanisms in determining the renal involvement are still unclear. We describe pathophysiology, histological features and clinical manifestations of the most frequent psychological eating disorders: AN and BN. Regarding AN, we analyze the recent literature, and identify 3 principal pathways towards renal involvement: chronic dehydration-hypokalemia, nephrocalcinosis and chronic rhabdomyolysis. Regarding BN, we describe the correlation between obesity and many proinflammatory cytokines, chemokines, growth factors and adipokines, having potential metabolic and hemodynamic effects on the kidney and an important role in the pathogenesis of obesity-related renal injury, independently of hypertension and diabetes.
RAGE Does Not Contribute to Renal Injury and Damage upon Ischemia/Reperfusion-Induced Injury
Authors: Dessing Mark C. , Pulskens Wilco P. , Teske Gwendoline J. , Butter Loes M. , van der Poll Tom , Yang Huan , Tracey Kevin J. , Nawroth Peter P. , Bierhaus Angelika , Florquin Sandrine , Leemans Jaklien C.
Published: November 2011

The receptor for advanced glycation end products (RAGE) mediates a variety of inflammatory responses in renal diseases, but its role in renal ischemia/reperfusion (I/R) injury is unknown. We showed that during renal I/R, RAGE ligands HMGB1 and S100B are expressed. However, RAGE deficiency does not affect renal injury and function upon I/R-induced injury.
ApoE Suppresses Atherosclerosis by Reducing Lipid Accumulation in Circulating Monocytes and the Expression of Inflammatory Molecules on Monocytes and Vascular Endothelium
Authors: Gaudreault Nathalie , Kumar Nikit , Posada Jessica M. , Stephens Kyle B. , Reyes de Mochel Nabora Soledad , Eberlé Delphine , Olivas Victor R. , Kim Roy Y. , Harms Matthew J. , Johnson Sean , Messina Louis M. , Rapp Joseph H. , Raffai Robert L.
Published: November 2011

Objective—

We investigated atheroprotective properties of apolipoprotein (apo) E beyond its ability to lower plasma cholesterol. We hypothesized that apoE reduces atherosclerosis by decreasing lipid accumulation in circulating monocytes and the inflammatory state of monocytes and the vascular endothelium.

Methods and Results—

We developed mice with spontaneous hyperlipidemia with and without plasma apoE. Hypomorphic apoE mice deficient in low-density lipoprotein receptor (
Apoe
h/h
Ldlr
−/−
) were compared to
Apoe
−/−
Ldlr
−/−
mice. Despite 4-fold more plasma apoE than WT mice,
Apoe
h/h
Ldlr
−/−
mice displayed similar plasma cholesterol as
Apoe
−/−
Ldlr
−/−
mice but developed 4-fold less atherosclerotic lesions by 5 months of age. The aortic arch of
Apoe
h/h
Ldlr
−/−
mice showed decreased endothelial expression of ICAM-1, PECAM-1, and JAM-A. In addition,
Apoe
h/h
Ldlr
−/−
mice had less circulating leukocytes and proinflammatory Ly6C
high
monocytes. These monocytes had decreased neutral lipid content and reduced surface expression of ICAM-1, VLA-4, and L-Selectin.
Apoe
h/h
Ldlr
−/−
mice displayed increased levels of apoA1-rich HDL that were potent in promoting cellular cholesterol efflux.

Conclusions—

Our findings suggest that apoE reduces atherosclerosis in the setting of hyperlipidemia by increasing plasma apoA1-HDL that likely contribute to reduce intracellular lipid accumulation and thereby the activation of circulating leukocytes and the vascular endothelium.
Stroke Epidemiology, Patterns of Management, and Outcomes in Fortaleza, Brazil
Authors: de Carvalho João José Freitas , Alves Monique Bueno , Viana Georgiana Álvares Andrade , Machado Cícera Borges , dos Santos Bento Fortunato Cardoso , Kanamura Alberto Hideki , Lottenberg Claudio Luiz , Neto Miguel Cendoroglo , Silva Gisele Sampaio
Published: November 2011

Background and Purpose—

Little information exists on the epidemiology and patterns of treatment of patients admitted to Brazilian hospitals with stroke. Our objective was to describe the frequency of risk factors, patterns of management, and outcome of patients admitted with stroke in Fortaleza, the fifth largest city in Brazil.

Methods—

Data were prospectively collected from consecutive patients admitted to 19 hospitals in Fortaleza with a diagnosis of stroke or transient ischemic attack from June 2009 to October 2010.

Results—

We evaluated 2407 consecutive patients (mean age, 67.7±14.4 years; 51.8% females). Ischemic stroke was the most frequent subtype (72.9%) followed by intraparenchymal hemorrhage (15.2%), subarachnoid hemorrhage (6.0%), transient ischemic attack (3%), and undetermined stroke (2.9%). The median time from symptoms onset to hospital admission was 12.9 (3.8–32.5) hours. Hypertension was the most common risk factor. Only 1.1% of the patients with ischemic stroke received thrombolysis. The median time from hospital admission to neuroimaging was 3.4 (1.2–26.5) hours. In-hospital mortality was 20.9% and the frequency of modified Rankin Scale score ≤2 at discharge was less than 30%. Older age, prestroke disability, and having a depressed level of consciousness at admission were independent predictors of poor outcome; conversely, male gender was a predictor of good outcome.

Conclusions—

The prevalence of stroke risk factors and clinical presentation in our cohort were similar to previous series. Treatment with thrombolysis and functional independency after a stroke admission were infrequent. We also found long delays in hospital admission and in evaluation with neuroimaging and high in-hospital mortality.
The X-Chromosome Has a Different Pattern of Gene Expression in Women Compared With Men With Ischemic Stroke
Authors: Stamova Boryana , Tian Yingfang , Jickling Glen , Bushnell Cheryl , Zhan Xinhua , Liu Dazhi , Ander Bradley P. , Verro Piero , Patel Vihar , Pevec William C. , Hedayati Nasim , Dawson David L. , Jauch Edward C. , Pancioli Arthur , Broderick Joseph P. , Sharp Frank R.
Published: November 2011

Background and Purpose—

Differences in ischemic stroke between men and women have been mainly attributed to hormonal effects. However, sex differences in immune response to ischemia may exist. We hypothesized that differential expression of X-chromosome genes in blood immune cells contribute to differences between men and women with ischemic stroke.

Methods—

RNA levels of 683 X-chromosome genes were measured on Affymetrix U133 Plus2.0 microarrays. Blood samples from patients with ischemic stroke were obtained at ≤3 hours, 5 hours, and 24 hours (n=61; 183 samples) after onset and compared with control subjects without symptomatic vascular diseases (n=109). Sex difference in X-chromosome gene expression was determined using analysis of covariance (false discovery rate ≤0.05, fold change ≥1.2).

Results—

At ≤3, 5, and 24 hours after stroke, there were 37, 140, and 61 X-chromosome genes, respectively, that changed in women; and 23, 18, and 31 X-chromosome genes that changed in men. Female-specific genes were associated with post-translational modification, small-molecule biochemistry, and cell–cell signaling. Male-specific genes were associated with cellular movement, development, cell-trafficking, and cell death. Altered sex specific X-chromosome gene expression occurred in 2 genes known to be associated with human stroke, including galactosidase A and
IDS
, mutations of which result in Fabry disease and Hunter syndrome, respectively.

Conclusions—

There are differences in X-chromosome gene expression between men and women with ischemic stroke. Future studies are needed to decipher whether these differences are associated with sexually dimorphic immune response, repair or other mechanisms after stroke, or whether some of them represent risk determinants.
The Neural Underpinings of Simultanagnosia: Disconnecting the Visuospatial Attention Network
Authors: Chechlacz Magdalena , Rotshtein Pia , Hansen Peter C. , Riddoch Jane M. , Deb Shoumitro , Humphreys Glyn W.
Published: November 2011

Because of our limited processing capacity, different elements of the visual scene compete for the allocation of processing resources. One of the most striking deficits in visual selection is simultanagnosia, a rare neuropsychological condition characterized by impaired spatial awareness of more than one object at time. To decompose the neuroanatomical substrates of the syndrome and to gain insights into the structural and functional organization of visuospatial attention, we performed a systematic evaluation of lesion patterns in a group of simultanagnosic patients compared with patients with either (i) unilateral visuospatial deficits (neglect and/or extinction) or (ii) bilateral posterior lesions without visuospatial deficits, using overlap/subtraction analyses, estimation of lesion volume, and a lesion laterality index. We next used voxel-based morphometry to assess the link between different visuospatial deficits and gray matter and white matter (WM) damage. Lesion overlap/subtraction analyses, lesion laterality index, and voxel-based morphometry measures converged to indicate that bilateral parieto-occipital WM disconnections are both distinctive and necessary to create symptoms associated with simultanagnosia. We also found that bilateral gray matter damage within the middle frontal area (BA 46), cuneus, calacarine, and parieto-occipital fissure as well as right hemisphere parietal lesions within intraparietal and postcentral gyri were associated with simultanagnosia. Further analysis of the WM based on tractography revealed associations with bilateral damage to major pathways within the visuospatial attention network, including the superior longitudinal fasciculus, the inferior fronto-occipital fasciculus, and the inferior longitudinal fasciculus. We conclude that damage to the parieto-occipital regions and the intraparietal sulcus, together, with bilateral WM disconnections within the visuosptial attention network, contribute to poor visual processing of multiple objects and the loss of processing speed characteristic of simultanagnosia.
Mechanisms Linking Volcanic Aerosols to the Atlantic Meridional Overturning Circulation
Authors: Iwi Alan M. , Hermanson Leon , Haines Keith , Sutton Rowan T.
Published: November 2011

This study examines the sensitivity of the climate system to volcanic aerosol forcing in the third climate configuration of the Met Office Unified Model (HadCM3). The main test case was based on the 1880s when there were several volcanic eruptions, the well-known Krakatau being the largest. These eruptions increased atmospheric aerosol concentrations and induced a period of global cooling surface temperatures. In this study, an ensemble of HadCM3 has been integrated with the standard set of radiative forcings and aerosols from the Intergovernmental Panel on Climate Change Fourth Assessment Report simulations, from 1860 to present. A second ensemble removes the volcanic aerosols from 1880 to 1899. The all-forcings ensemble shows an attributable 1.2-Sv (1 Sv ≡ 106 m3 s−1) increase in the Atlantic meridional overturning circulation (AMOC) at 45°N—with a 0.04-PW increase in meridional heat transport at 40°N and increased northern Atlantic SSTs—starting around 1894, approximately 11 years after the first eruption, and lasting a further 10 years at least. The mechanisms responsible are traced to the Arctic, with suppression of the global water cycle (high-latitude precipitation), which leads to an increase in upper-level Arctic and Greenland Sea salinities. This then leads to increased convection in the Greenland–Iceland–Norwegian (GIN) Seas, enhanced Denmark Strait overflows, and AMOC changes with density anomalies traceable southward along the western Atlantic boundary. The authors investigate whether a similar response to the Pinatubo eruption in 1991 could still be ongoing, but do not find strong evidence.
The Usefulness of Piecewise Potential Vorticity Inversion
Authors: Røsting Bjørn , Kristjánsson Jón Egill
Published: November 2011

It is today widely accepted that potential vorticity (PV) thinking is a highly useful approach for understanding important aspects of dynamic meteorology and for validation of output from state-of-the-art numerical weather prediction (NWP) models. Egger recently presented a critical view on piecewise potential vorticity inversion (PPVI). This was done by defining a PV anomaly by retaining the observed PV field in a specific region, while changing the observed PV fields to zero elsewhere. Inversion of such a modified PV field yields a flow vastly different from the observed. On the basis of this result it was argued that PPVI is useless for understanding the dynamics of the flow.

The present paper argues that the results presented by Egger are incomplete in the context of PPVI, since the complementary cases were not considered and that the results also depend on the idealized model formulations. The complementary case is defined by changing the observed PV to zero in the specific region, while retaining the observed PV field elsewhere.

By including the complementary cases, it can be demonstrated that the streamfunction fields associated with the PV and boundary temperature anomalies presented by Egger add up to yield the observed streamfunction field, as expected if PPVI is to be valid. It follows that PPVI is indeed valid and useful in these cases.
Analytic Solutions for Evolving Size Distributions of Spherical Crystals or Droplets Undergoing Diffusional Growth in Different Regimes
Authors: Lewellen D. C.
Published: November 2011

Motivated by simulations of slow-growing contrail cirrus, the solution of the diffusional growth equations for a population of spherical ice crystals or water droplets is reexamined. For forcing specified by the evolution of the total water content above saturation within a parcel (whether driven by vertical motions, radiative heating, turbulent mixing, etc.) three behavior regimes are identified: “very fast growth” that cannot equilibrate, “fast growth” with a narrowing size spectrum, and “slow growth” with a broadening spectrum. The boundaries between regimes, time scales involved, and evolution of the condensate mass, number, and supersaturation are determined. The slow-growth regime represents an example of “spectral ripening,” with crystal or droplet numbers falling in time because of surface tension effects. Surprisingly the diffusional growth equations for the size spectrum evolution can be solved exactly in this case: in appropriate coordinates the spectral shape becomes steady, crystal or droplet numbers fall as a forcing-dependent power law, and the mean particle mass grows linearly with time. Dependence on different physical variables, fluctuating forcing, and modifications due to kinetic theory corrections are all considered. In the limit of zero external forcing on the parcel the size-spectrum solution is mathematically equivalent to a classic result in the theory of Ostwald ripening of solid solutions. It is argued that the slow-growth regime may be important in the evolution of contrail cirrus and perhaps in setting upper limits on droplet number densities in stratiform boundary layer clouds. The theoretical results are compared with parcel model simulations for illustration and to study numerical issues in binned microphysics models.
Courts as Coordinators
Authors: Johns Leslie
Published: November 2011

Why do states build international courts, submit cases, and enforce court judgments? This article examines the role of a court that is neither a “decider” nor an “information provider.” Litigation is costly and does not reveal private information. The court’s ruling is not binding and bargaining can occur before and after the court has ruled. Nevertheless, an alternative dispute resolution mechanism emerges: court rulings can coordinate endogenous multilateral enforcement. Disinterested states will enforce to ensure that they can profitably use the court in the future. Accepting jurisdiction of the court allows a state to make efficiency-enhancing “trades,” winning high-value disputes in exchange for losing low-value disputes. This is possible because litigation is a screening device: states only sue when they derive relatively high value from the disputed asset. The use of the court as a coordination device for multilateral enforcement allows for the existence of a court with endogenous enforcement and jurisdiction.
Beautiful Thus Innocent? The Impact of Defendants' and Victims' Physical Attractiveness and Participants' Rape Beliefs on Impression Formation in Alleged Rape Cases
Authors: Vrij Alder , Firmin Hannah R.
Published: November 2011

This experiment examined the possible beneficial effects of victims' and defendants' good-looks in an alleged rape case. It was hypothesized that people who especially endorsed ‘Rape Myths’ would be more favourable towards victims and defendants who are good-looking. Moreover, it was hypothesized that females would be more favourable towards the victim than males and that this gender difference would be mediated by differences in “Rape Myths Acceptance”.

In the experiment, 80 observers were exposed to an extract of a victim's story about an alleged rape case. The physical attractiveness of both the victim and the defendant were systematically varied. Observers' Rape Myths Acceptance were measured with Burt's (1980) Rape Myths Acceptance scale. The results support the hypotheses; it is therefore suggested that the acceptance of these myths should be investigated in selection procedures of people who are likely to be confronted with victims of sexual offenses, such as police officers and jury members in rape or sexual harassment cases.
Refugees and Asylum Seekers as Victims: The Australian Case
Authors: Jupp James
Published: November 2011

Australia has had two centuries of state planned and controlled immigration, with official policies excluding those felt undesirable for racial, social or economic reasons, Visa controls have been tightened in recent years even against the previously welcomed British. Australia has also accepted refugees for permanent settlement under the 1951 UN Convention. Since the 1990s this approach has been steadily modified, making it increasingly difficult to achieve settlement as an asylum seeker. Detention in prison-like camps, limitation of the right to permanent residence, and policies designed to expedite homeland return have all led to victimisation of the relatively small numbers seeking asylum outside the universal visa system. This has been accompanied by forcible removal to locations outside Australian territory and attempts to limit rights of appeal. Official demonisation of asylum seekers has damaged public acceptance of refugees, while draconian policies towards them have undermined Australia’s previous reputation as a safe haven.
The Disassociation Between Domestic Violence Service Provision and Multi-Agency Initiatives on Domestic Violence
Authors: Welsh Kirsty
Published: November 2011

In recent years in England and Wales, the multi-agency approach has come to be increasingly promoted in government circles as a response in domestic violence. In this article, I reflect on doctoral research to question the assumption that the multi-agency approach should be celebrated as a leading response to the problem. Rather, I argue that such approaches increase neither women's protection nor their safety. Focusing on findings from two research areas in Northern England, I argue that there was a separation or disassociation between multi-agency domestic violence initiatives and service provision in these areas. I illustrate the argument using three examples from the research. Other issues are important in founding the argument that such approaches are not increasing women's protection or safety. These issues centre on the interaction between service provision and prevention. I argue that, because appropriate service provision is essential in preventing domestic violence, an approach that is not grounded in service provision but is disassociated from it can do little to prevent domestic violence and protect women.
Do African Immigrants in Turku Experience More Racist Harassment in Finland? A Victim-Oriented-Approach
Authors: Egharevba Stephen
Published: November 2011

Harassment of immigrant citizens due to their race, colour and national origin is still a disturbing phenomenon in the streets, homes, restaurants, shops, and schools, as well as in the universities across Finland. This harassment and intimidation is usually racially motivated and creates fear in the minds of many African immigrants in Turku. My objective in this paper is to try to understand and evaluate racial harassment and the frequency with which African immigrants experience racial hostility on the streets in Turku. In addition, this is an attempt to identify the characteristics which tend to precipitate racially motivated forms of harassment. Finally, I will also be exploring the reasons why so few official complaints of racial harassment are made to the police. To address these issues of harassment and intimidation, 120 African immigrants were surveyed through a prepared questionnaire and semi-structured interviews were subsequently carried out with 25 of these. The study revealed that the majority of respondents had frequently experienced harassment on the streets, outside restaurants and by their neighbours. In general, males seemed to experience a higher level of harassment due to their frequent excursions in the evenings and at night in Turku. Overall, this study revealed that African immigrants are still sceptical about reporting racially-motivated crimes to the authorities due to the distance between them and the police in Turku. There is a need to raise awareness amongst African immigrants in this city in order for the police to win back their confidence, since they are presently very sceptical of the Finnish police.
Victimology Between the Local and the Global
Authors: Shalhoub-Kevorkian Nadera , Braithwaite John
Published: November 2011

This special issue is about victimization as a very personal experience that is profoundly susceptible to communal forgetting. It includes an important quantitative contribution in the conventional routine activities theory tradition. At the same time, it challenges conventional victimological examinations, while raising critical race, class and gendered issues. The essays herein help us to see more abstract architectures of routine activity that channel whole societies and the entire global community to see victimization or to be wilfully blind to it; to classify victimization into legal categories that neuter it or that acknowledge it; that silence victims or listen to them; that promote collective amnesia or collective memory and to propose new critical lenses to the study of victimology. To connect local experience of victimization to global transformation at least several loops of learning are needed. Perhaps the art of liberating victims is figuring out how to link local loops of learning from personal stories to more encompassing loops through events like national enquiries, up to institutions like the International Criminal Court. When national loops of learning wilfully obstruct international learning from the experience of victims, victim advocates must figure out how to by-pass obstructive intermediate communication loops. They must use modalities like the internet and NGO networks to connect to different loops of communication that will take their experience more seriously. Victimology between the local and the global aims at challenging globalized and localized workings of power, by offering localized voices of victims that allow theorizing bottom up. Yet, and at the same time, it hopes to challenge localized architectures and geographies of power that construct and re-produce victimization, while offering larger theoretical critical directions.
17β-Estradiol (E-2) administration to male (NZB × SWR)F1 mice results in increased IdLNF1-reactive memory T-lymphocytes and accelerated glomerulonephritis
Authors: Feng F , Silvin CJ , Fiore NC , Stoll ML , Price KE , Shanley PS , Silverstone AE , Gavalchin J
Published: November 2011

While it has been shown that estradiol treatment accelerates the onset of lupus nephritis with autoantibody production and kidney damage in both male and female lupus-prone mice, the specific mechanism(s) involved are unknown. Our previous work has shown that alterations in IdLNF1-reactive T cells and IdLNF1+ antibodies correlated closely with the onset of autoimmune nephritis in female F1 progeny of SWR and NZB (SNF1) mice, supporting a critical role for the IdLNF1 idiotype in the development of disease. Since male SNF1 mice normally do not develop nephritis, we tested whether administration of 17β-estradiol (E-2) to male SNF1 mice would increase IdLNF1 IgG levels and autoreactive T cells, and further, induce nephritis. We found that E-2-treated male SNF1 mice developed nephritis with the same time course and mean survival as normal female SNF1 mice. Moreover, it appeared that the mechanism involved increased serum IdLNF1+IgG and its deposition in kidney glomeruli, preceded by astriking twofold increase in T-lymphocytes expressing the memory phenotype (CD44+CD45RBlo) predominantly in the IdLNF1-reactive T-cell population. In addition, we noted that cells with this phenotype were increased in the nephritic kidneys of treated mice, suggesting a direct involvement of those cells in the renal pathology. E-2 treatment also induced increased numbers of pathogenic IdLNF1+ antibody-producing B cells and elevated presentation of pathogenic IdLNF1+ peptide. Taken together, these results suggest a mechanism of E-2-induced acceleration of autoimmune disease in lupus-prone mice may involve expansion of autoreactive idiotypic T and B-cell populations.
War of Words: Bridging the Language Divide in the Great War
Authors: Constantine Simon
Published: November 2011

This article explores the different ways in which soldiers in the First World War communicated with the enemy. Drawing, in particular, on accounts of capture and captivity recorded in interview with escaped and exchanged British prisoners of war, it argues that language was central to these experiences, and that a soldier’s ability to understand, and make himself understood, was often pivotal to the question of whether he survived or perished.
Perspectives of Nursing Faculty About Nursing in Iraq
Authors: Al-Da’mi Lahay A. Hussain , Boyle Joyceen S.
Published: November 2011

Purpose: Long standing problems are apparent in professional nursing in Iraq. This is a critical point in time and feedback and input from nurses will be important in advancing the profession. Design: A questionnaire was used to explore the attitudes of faculty members about professional nursing, women’s roles and nursing, and the Iraqi Nurses Association. The questionnaire was administered to 31 faculty members at the College of Nursing, University of Baghdad. Findings: The respondents reported the poor image of Iraqi nursing and the relationship between physicians and nurses as the most immediate problems facing the profession. The respondents are not active in their professional association and believe that the association is not addressing current problems. Profound changes are needed in professional nursing before nurses can play significant roles in the Iraqi health care system.
Interactions in and between Strategic Action Fields
Authors: Özen Hayriye , Özen Şükrü
Published: November 2011

This study addresses how multinational corporations and protesters in an environmental struggle learn from the proximate struggles within the same field and how they structure the broader institutional field. Drawing on the literature integrating the social movement and new institutional theory, particularly the “strategic action fields” (SAFs) approach of Fligstein and McAdam, the authors comparatively study the interactions in and between two sequential environmental struggles in the field of gold mining in Turkey. The findings suggest that the interactive processes in an SAF and their consequences are largely built on the lessons drawn from both “successes” and “failures” in the proximate SAF that preceded it. Furthermore, those actors that act proactively are more likely to stabilize the SAF according to their interests. Finally, state interventions from the outside create temporary stability that involves the acquiescence of challengers, whereas the consent-seeking actions of incumbents are more likely to generate a permanent stability, stabilizing the broader field.