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I am not able to find the file with supplementary methods of the present paper. Can somebody help me to find it ?
i could not find the supplementary data for this paper. please help me find them. thank you
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Articles from this Volume

Charles C Chu, Lu Zhang, Arjun Dhayalan, Briana M Agagnina, Amanda R Magli, Gia Fraher, Sebastien Didier, Linda P Johnson, William J Kennedy, Rajendra N Damle, Xiao-Jie Yan, Piers E M Patten, Saul Teichberg, Prasad Koduru, Jonathan E Kolitz, Steven L Allen, Kanti R Rai, and Nicholas Chiorazzi more...
Posted by Leah Caracappa on May 14, 2012 9:26 AM CDT
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Posted by Leah Caracappa on Dec 15, 2011 12:00 AM CST
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Posted by Leah Caracappa on Dec 14, 2011 12:00 AM CST
Review Article

Michał Kukla, Włodzimierz Mazur, Rafał J Bułdak, and Krystyna Zwirska-Korczala

Chronic hepatitis C (CHC) is generally a slowly progressive disease, but some factors associated with rapid progression have been identified. Steatosis, independently of its metabolic or viral origin, leads to liver injury and fibrosis. It is suggested that hepatitis C virus may contribute to a wide spectrum of metabolic disturbances—namely, steatosis, insulin resistance, increased prevalence of impaired glucose tolerance, type 2 diabetes mellitus and lipid metabolism abnormalities. Adipokines, which are produced mainly by adipose tissue, may influence the inflammatory response and insulin sensitivity and contribute to the development of metabolic abnormalities in CHC and also regulate fibrogenesis and angiogenesis. Visfatin was described as an adipokine with immunomodulating and proinflammatory properties that promotes B-cell maturation and enhances activation of leukocytes, synthesis of adhesion molecules and production of proinflammatory cytokines. Visfatin exerts insulin-mimetic effects, decreases plasma glucose levels and regulates cell energy balance. Chemerin stimulates chemotaxis of dendritic cells, macrophages and natural killer (NK) cells toward the site of inflammation. On the other hand, it inhibits synthesis of proinflammatory mediators and enhances adiponectin production, influences adipocyte differentiation and maturation and regulates glucose uptake in adipocytes. Vaspin expression in human adipose tissue seems to be a compensatory mechanism associated with obesity and insulin resistance. Vaspin suppresses leptin, tumor necrosis factor (TNF)-ooand resistin expression. Leptin protects against liver steatosis but accelerates fibrosis progression and exacerbates the inflammatory process. In contrast, adiponectin exerts a hepatoprotective effect. In this report, data indicating a possible role of these adipokines in the pathogenesis of chronic hepatitis are summarized.

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Posted by Leah Caracappa on Dec 13, 2011 12:00 AM CST
Review Article

Ning Wang, Nan Shen, Timothy J Vyse, Vidya Anand, Iva Gunnarson, Gunnar Sturfelt, Solbritt Rantapää-Dahlqvist, Kerstin Elvin, Lennart Truedsson, Bengt A Andersson, Charlotte Dahle, Eva Örtqvist, Peter K Gregersen, Timothy W Behrens, and Lennart Hammarström

Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety of concomitant autoimmune diseases. In this review, we present data on the prevalence of IgAD in patients with Graves disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD), myasthenia gravis (MG) and rheumatoid arthritis (RA) on the basis of both our own recent large-scale screening results and literature data. Genetic factors are important for the development of both IgAD and various autoimmune disorders, including GD, SLE, T1D, CD, MG and RA, and a strong association with the major histocompatibility complex (MHC) region has been reported. In addition, non-MHC genes, such as interferon-induced helicase 1 (IFIH1) and c-type lectin domain family 16, member A (CLEC16A), are also associated with the development of IgAD and some of the above diseases. This indicates a possible common genetic background. In this review, we present suggestive evidence for a shared genetic predisposition between these disorders.

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Posted by Leah Caracappa on Dec 12, 2011 12:00 AM CST
Zhe Dong, Tingting Wu, Weidong Qin, Chuankai An, Zhihao Wang, Mingxiang Zhang, Yun Zhang, Cheng Zhang, and Fengshuang An

Although serum amyloid A (SAA) is an excellent marker for coronary artery disease, its direct effect on atherogenesis in vivo is obscure. In this study we investigated the direct effect of SAA on promoting the formation of atherosclerosis in apolipoprotein E–deficient (ApoE–/–) mice. Murine SAA lentivirus was constructed and injected into ApoE–/– mice intravenously. Then, experimental mice were fed a chow diet (5% fat and no added cholesterol) for 14 wks. The aortic atherosclerotic lesion area was larger with than without SAA treatment. With increased SAA levels, the plasma levels of interleukin-6 and tumor necrosis factor-α were significantly increased. Macrophage infiltration in atherosclerotic regions was enhanced with SAA treatment. A migration assay revealed prominent dose-dependent chemotaxis of SAA to macrophages. Furthermore, the expression of monocyte chemotactic protein-1 and vascular cell adhesion molecule-1 (VCAM-1) was upregulated significantly with SAA treatment. SAA-induced VCAM-1 production was detected in human aortic endothelial cells in vitro. Thus, an increase in plasma SAA directly accelerates the progression of atherosclerosis in ApoE–/– mice. SAA is not only a risk marker for atherosclerosis but also an active participant in atherogenesis.

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Posted by Leah Caracappa on Dec 9, 2011 12:00 AM CST
Meggan Mackay, Mathew P Bussa, Cynthia Aranow, Aziz M Ulug, Bruce T Volpe, Patricio T Huerta, Miklos Argyelan, Arthur Mandel, Joy Hirsch, Betty Diamond, and David Eidelberg

The mediators of tissue damage in systemic lupus erythematosus (SLE) such as antibodies, cytokines and activated immune cells have direct access to most organs in the body but must penetrate the blood-brain barrier (BBB) to gain access to brain tissue. We hypothesized that compromise of the BBB occurs episodically such that the brain will acquire tissue damage slowly and not at the same rate as other organs. On the basis of these assumptions, we wished to determine if duration of disease correlated with brain injury, as measured with functional magnetic resonance imaging (fMRI), and if this was independent of degree of tissue damage in other organs. We investigated differences in brain activation patterns using fMRI in 13 SLE patients stratified by disease duration of ≤2 years (short-term [ST]) or ≥10 years (long-term [LT]). Two fMRI paradigms were selected to measure working memory and emotional response (fearful faces task). Performance in the working memory task was significantly better in the ST group for one and two shape recall; however, both groups did poorly with three shape recall. Imaging studies demonstrated significantly increased cortical activation in the ST group in regions associated with cognition during the two shape retention phase of the working memory task (P < 0.001) and increased amygdala (P < 0.05) and superior parietal (P < 0.01) activation in response to the fearful faces paradigm. In conclusion, analysis of activation patterns stratified by performance accuracy, differences in comorbid disease, corticosteroid doses or disease activity suggests that these observed differences are attributable to SLE effects on the central nervous system exclusive of vascular disease or other confounding influences. Our hypothesis is further supported by the lack of correlation between regional brain abnormalities on fMRI and the Systemic Lupus International Collaborating Clinics (SLICC) damage index.

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Posted by Leah Caracappa on Dec 8, 2011 12:00 AM CST
Hannelore Ehrenreich, Anne Kästner, Karin Weissenborn, Jackson Streeter, Swetlana Sperling, Kevin K Wang, Hans Worthmann, Ronald L Hayes, Nico von Ahsen, Andreas Kastrup, Andreas Jeromin, and Manfred Herrmann

The German Multicenter EPO Stroke Trial, which investigated safety and efficacy of erythropoietin (EPO) treatment in ischemic stroke, was formally declared a negative study. Exploratory subgroup analysis, however, revealed that patients not receiving thrombolysis most likely benefited from EPO during clinical recovery, a result demonstrated in the findings of the Göttingen EPO Stroke Study. The present work investigated whether the positive signal on clinical outcome in this patient subgroup was mirrored by respective poststroke biomarker profiles. All patients of the German Multicenter EPO Stroke Trial nonqualifying for thrombolysis were included if they (a) were treated per protocol and (b) had at least two of the five follow-up blood samples for circulating damage markers drawn (n = 163). The glial markers S100B and glial fibrillary acid protein (GFAP) and the neuronal marker ubiquitin C-terminal hydrolase (UCH-L1) were measured by enzyme-linked immunosorbent assay in serum on d 1, 2, 3, 4 and 7 poststroke. All biomarkers increased poststroke. Overall, EPO-treated patients had significantly lower concentrations (area under the curve) over 7 d of observation, as reflected by the composite score of all three markers (Cronbach α = 0.811) and by UCH-L1. S100B and GFAP showed a similar tendency. To conclude, serum biomarker profiles, as an outcome measure of brain damage, corroborate an advantageous effect of EPO in ischemic stroke. In particular, reduction in the neuronal damage marker UCH-L1 may reflect neuroprotection by EPO.

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Posted by Leah Caracappa on Dec 4, 2011 12:00 AM CST
M Hadi Falahatpisheh, Adrian Nanez, and Kenneth S Ramos

Mounting evidence suggests that the blueprint of chronic renal disease is established during early development by environmental cues that dictate alterations in differentiation programming. Here we show that aryl hydrocarbon receptor (AHR), a ligand-activated basic helix-loop-helix-PAS homology domain transcription factor, disrupts murine renal differentiation by interfering with Wilms tumor suppressor gene (WT1) signaling in the developing kidney. Embryonic kidneys of C57BL/6J Ahr–/– mice at gestation d (GD) 14 showed reduced condensation in the nephrogenic zone and decreased numbers of differentiated structures compared with wild-type mice. These deficits correlated with increased expression of the (+) 17aa Wt1 splice variant, decreased mRNA levels of Igf-1 rec., Wnt-4 and E-cadherin, and reduced levels of 52 kDa WT1 protein. AHR knockdown in wild-type embryonic kidney cells mimicked these alterations with notable increases in (+) 17aa Wt1 mRNA, reduced levels of 52 kDa WT1 protein, and increased (+) 17aa 40-kDa protein. AHR downregulation also reduced Igf-1 rec., Wnt-4, secreted frizzled receptor binding protein-1 (sfrbp-1) and E-cadherin mRNAs. In the case of Igf-1 rec. and Wnt-4, genetic disruption was fully reversed upon restoration of cellular Wt1 protein levels, confirming that functional interactions between AHR and Wt1 represent a likely molecular target for renal developmental interference.

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Posted by Leah Caracappa on Dec 1, 2011 12:00 AM CST
Zhu Yuan, Kang Cao, Chao Lin, Lei Li, Huan-yi Liu, Xin-yu Zhao, Lei Liu, Hong-xin Deng, Jiong Li, Chun-lai Nie, and Yu-quan Wei

Ovarian cancer is the number one cause of death from gynecologic malignancy. A defective p53 pathway is a hallmark of ovarian carcinoma. The p53 mutation correlates significantly with resistance to platinum-based chemotherapy, early relapse and shortened overall survival in ovarian cancer patients. PUMA (p53 upregulated modulator of apoptosis), a BH3-only Bcl-2 family protein, was recently identified as a transcriptional target of p53 and a potent apoptosis inducer in various cancer cells. In this study, we showed that the induction of PUMA by cisplatin was abolished in p53-deficient SKOV3 cells. Elevated expression of PUMA- induced apoptosis and sensitized A2780s and SKOV3 ovarian cancer cells to cisplatin, and the combination of PUMA and low-dose cisplatin, significantly suppressed xenograft tumor growth in vivo through enhanced induction of apoptosis compared with treatment with PUMA or cisplatin alone. The effects of PUMA were mediated by enhanced caspase activation and release of cytochrome c and Smac (second mitochondria–derived activator of caspase) into the cytosol. Furthermore, PUMA chemosensitized intrinsically resistant SKOV3 cells to cisplatin through downregulation of B-cell lymphoma-extra large (Bcl-xL) and myeloid cell leukemia sequence 1 (Mcl-1). PUMA-mediated Bcl-xL downregulation mainly happened at the transcription level, whereas PUMA-induced Mcl-1 downregulation
was associated with caspase- dependent cleavage and proteasome-mediated degradation. To our knowledge, these data suggest a new mechanism by which overexpression of PUMA enhances sensitivity of SKOV3 cells to cisplatin by lowering the threshold set simultaneously by Bcl-xL and Mcl-1. Taken together, our findings indicate that PUMA is an important modulator of therapeutic responses of ovarian cancer cells and is potentially useful as a chemosensitizer in ovarian cancer therapy.

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Posted by Leah Caracappa on Nov 17, 2011 12:00 AM CST
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