320 research outputs found

    Analisis Faktor Faktor Yang Mempengaruhi Opini Going Concern

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    Penelitian ini bertujuan untuk menguji adanya pengaruh audit tenure, reputasi KAP, disclosure, debt default terhada penerimaan opini audit going concern. Hipotesis yang diajukan adalah (1) Audit tenure berpengaruh terhadap penerimaan opini audit going concern, (2) Reputasi auditor berpengaruh terhadap penerimaan opini audit going concern, (3) Disclosr berpengaruh terhadap penerimaan opini audit going concern, (4) Debt Default berpengauh terhadap penerimaan opini audit going cocern. Penelitian ini dilakukan dengan menggunakan 15 perusahaan manufaktur yang listing di BEI pada tahun 2008-2011. Sampel dipilih dengan menggunakan metode purposive sampling. Data dianilisis dengan menggunakan model analisis regresi logistik. Hasil penelitian menunjukkan bahwa audit tenure, reputasi KAP dan disclosure tidak berpengaruh terhadap penerimaan opini audit going concern. deb default memiliki pengaruh terhadap penerimaan opini audit going concern

    Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

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    Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

    Use of a Javidâ„¢ shunt in the management of axillary artery injury as a complication of fracture of the surgical neck of the humerus: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Axillary artery injury is a rare but severe complication of fractures of the surgical neck of the humerus.</p> <p>Case presentation</p> <p>We present a case of axillary artery pseudoaneurysm secondary to such a fracture, in a 82-year-old white woman, presenting 10 weeks after the initial injury, successfully treated with subclavian to brachial reversed vein bypass together with simultaneous open reduction and internal fixation of the fracture. We discuss the use of a Javidâ„¢ shunt during combined upper limb revascularisation and open reduction and internal fixation of the fractured humerus.</p> <p>Conclusion</p> <p>This case highlights the usefulness of a Javidâ„¢ shunt, over other forms of vascular shunts, in prompt restoration of blood flow to effect limb salvage. It can be considered as a temporary measure whilst awaiting definitive revascularisation which can be performed following fracture fixation.</p

    A Non-Invasive method of quantifying pancreatic volume in mice using micro-MRI

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    In experimental models of pancreatic growth and recovery, changes in pancreatic size are assessed by euthanizing a large cohort of animals at varying time points and measuring organ mass. However, to ascertain this information in clinical practice, patients with pancreatic disorders routinely undergo non-invasive cross-sectional imaging of the pancreas using magnetic resonance imaging (MRI) or computed tomography (CT). The aim of the current study was to develop a thinsliced, optimized sequence protocol using a high field MRI to accurately calculate pancreatic volumes in the most common experimental animal, the mouse. Using a 7 Telsa Bruker micro-MRI system, we performed abdominal imaging in whole-fixed mice in three standard planes: axial, sagittal, and coronal. The contour of the pancreas was traced using Vitrea software and then transformed into a 3-dimensional (3D) reconstruction, from which volumetric measurements were calculated. Images were optimized using heart perfusion-fixation, T1 sequence analysis, and 0.2 to 0.4 mm thick slices. As proof of principle, increases in pancreatic volume among mice of different ages correlated tightly with increasing body weight. In summary, this is the first study to measure pancreatic volumes in mice, using a high field 7 Tesla micro-MRI and a thin-sliced, optimized sequence protocol. We anticipate that micro-MRI will improve the ability to non-invasively quantify changes in pancreatic size and will dramatically reduce the number of animals required to serially assess pancreatic growth and recovery.© 2014 Paredes et al

    Global analysis of gene expression in response to L-Cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica

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    <p>Abstract</p> <p>Background</p> <p><it>Entamoeba histolytica</it>, an enteric protozoan parasite, causes amebic colitis and extra intestinal abscesses in millions of inhabitants of endemic areas. <it>E. histolytica </it>completely lacks glutathione metabolism but possesses L-cysteine as the principle low molecular weight thiol. L-Cysteine is essential for the structure, stability, and various protein functions, including catalysis, electron transfer, redox regulation, nitrogen fixation, and sensing for regulatory processes. Recently, we demonstrated that in <it>E. histolytica</it>, L-cysteine regulates various metabolic pathways including energy, amino acid, and phospholipid metabolism.</p> <p>Results</p> <p>In this study, employing custom-made Affymetrix microarrays, we performed time course (3, 6, 12, 24, and 48 h) gene expression analysis upon L-cysteine deprivation. We identified that out of 9,327 genes represented on the array, 290 genes encoding proteins with functions in metabolism, signalling, DNA/RNA regulation, electron transport, stress response, membrane transport, vesicular trafficking/secretion, and cytoskeleton were differentially expressed (≥3 fold) at one or more time points upon L-cysteine deprivation. Approximately 60% of these modulated genes encoded proteins of no known function and annotated as hypothetical proteins. We also attempted further functional analysis of some of the most highly modulated genes by L-cysteine depletion.</p> <p>Conclusions</p> <p>To our surprise, L-cysteine depletion caused only limited changes in the expression of genes involved in sulfur-containing amino acid metabolism and oxidative stress defense. In contrast, we observed significant changes in the expression of several genes encoding iron sulfur flavoproteins, a major facilitator super-family transporter, regulator of nonsense transcripts, NADPH-dependent oxido-reductase, short chain dehydrogenase, acetyltransferases, and various other genes involved in diverse cellular functions. This study represents the first genome-wide analysis of transcriptional changes induced by L-cysteine deprivation in protozoan parasites, and in eukaryotic organisms where L-cysteine represents the major intracellular thiol.</p

    Murine Pancreatic Adenocarcinoma Reduces Ikaros Expression and Disrupts T Cell Homeostasis

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    Background Maintenance of T cell immune homeostasis is critical for adequate anti-tumor immunity. The transcription factor Ikaros is essential for lymphocyte development including T cells. Alterations in Ikaros expression occur in blood malignancies in humans and mice. In this study, we investigated the role of Ikaros in regulating T cell immune balance in pancreatic cancer mouse models. Methodology and Principal Findings Using our Panc02 tumor-bearing (TB) mouse model, western blot analysis revealed a reduction in Ikaros proteins while qRT-PCR showed no differences in Ikaros mRNA levels in TB splenocytes compared to control. Treatment of naïve splenocytes with the proteasomal inhibitor, MG132, stabilized Ikaros expression and prevented Ikaros downregulation by Panc02 cells, in vitro. Western blot analyses showed a reduction in protein phosphatase 1 (PP1) and protein kinase CK2 expression in TB splenocytes while CK2 activity was increased. Immunofluorescence microscopy revealed altered punctate staining of Ikaros in TB splenocytes. Flow cytometry revealed a significant decrease in effector CD4+ and CD8+ T cell percentages but increased CD4+CD25+ regulatory T cells in TB splenocytes. Similar alterations in T cell percentages, as well as reduced Ikaros and CK2 but not PP1 expression, were observed in a transgenic, triple mutant (TrM) pancreatic cancer model. Ikaros expression was also reduced in enriched TB CD3+ T cells. MG132 treatment of naïve CD3+ T cells stabilized Ikaros expression in the presence of Panc02 cells. Western blots showed reduced PP1 and CK2 expression in TB CD3+ T cells. Conclusions/Significance The results of this study suggest that the pancreatic tumor microenvironment may cause proteasomal degradation of Ikaros, possibly via dysregulation of PP1 and CK2 expression and activity, respectively. This loss of Ikaros expression may contribute to an imbalance in T cell percentages. Ikaros may potentially be a therapeutic target to restore T cell homeostasis in pancreatic cancer hosts, which may be critical for effective anti-tumor immunity

    A physical activity intervention to improve the quality of life of patients with a stoma: a feasibility study

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    Background We hypothesise that a physical activity (PA) intervention will improve the quality of life (QoL) of people with a stoma. A feasibility study of the intervention and trial parameters is necessary to inform a future main trial. Methods Participants received a weekly PA consultation by telephone, video conferencing, or face-to-face for 12 weeks with a PA instructor who prescribed physical activities and supported participants by addressing stoma-related concerns and using behaviour change techniques. A feasibility study of the intervention and trial parameters was conducted in three UK sites using mixed methods. Results The number of eligible patients consenting to the study was 30 out of 174 (17%). Most participants were female (73%); 73% had an ileostomy and 27% a colostomy; mean time since diagnosis was 6 months. A total of 18 (64%) participants completed pre- (baseline) and post-intervention (follow-up) measures. Results show an improvement on all scales measuring QoL and disease-specific fatigue. The median PA consultation rate per participant was eight sessions. Participants reported completing 75% or more of the prescribed PA each week. Eight stoma-related themes were identified from qualitative interviews: fear of hernia, bending down, fatigue, pain, prolapse, surgical wounds, stoma appliance, and stigma. The intervention appeared to address these issues. Conclusion This feasibility study demonstrated that a novel manualised PA intervention for people with a stoma is safe, feasible, and acceptable, and shows promise for improving outcomes. However, difficulties with recruitment will need to be carefully considered to ensure the success of future studies in this area
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