bluuebunny/crossref_metadata_2025_split huggingface dataset:
Museums and Museum Studies in New Zealand: A Survey of Historical Developments
Authors: McCarthy Conal , Cobley Joanna 
Published: February 2009

AbstractWhat relationship has the university subject of museum studies had with the museum sector? It is often claimed that there is an oversupply of graduates in museum studies ill‐equipped to work in museums, an issue that reveals tensions between understandings of academic study and practical experience. This article addresses these tensions between museums and museum studies through a survey of the historical development of museums and the closely related development of training, professional development and university degrees. The generalist role of the museum worker in the embryonic museums of colonial New Zealand did not require formal academic training. The 1930s witnessed a turning point with grants for professional development from the Carnegie Corporation. The Second World War disrupted the museum sector but from the 1950s museums experienced rapid growth in type and number, developments requiring larger numbers of specialised staff. At the same time the International Council of Museums (ICOM) and the museum branch of UNESCO were formed, along with a national professional body The Art gallery and Museums Association of New Zealand (AGMANZ), which provided an international and local voice and focus for the museum sector. Finally, in the 1960s, only 100 years after the first museum was opened, we see the birth of museum‐centred training programmes first administered by the museum sector and in the late 1980s by the university. The article concludes that the increasingly complex and specialised museum profession and the increasingly sophisticated academic analysis of museums emerged at the same time and are inevitably and necessarily intertwined.
Phosphorylation of p70S6 kinase predicts overall survival in patients with clear margin‐resected hepatocellular carcinoma
Authors: Baba Hideo A. , Wohlschlaeger Jeremias , Cicinnati Vito R. , Hilgard Philip , Lang Hauke , Sotiropoulos Georgios C. , Takeda Atsushi , Beckebaum Susanne , Schmitz Klaus J. 
Published: February 2009

AbstractBackground/Aims: The mammalian target of rapamycin (mTOR) inhibitors play a key role in regulating signal transduction by blocking the mTOR pathway and combining anticancer and immunosuppressive properties. This study was undertaken to determine the prevalence and clinicopathological relevance of phospho‐p70S6 (p‐p70S6) kinase in hepatocellular carcinoma (HCC) and to investigate the effects of rapamycin on HCC in vitro.Methods: A total of 196 patients with HCCs were treated either with surgical resection (n=106) or liver transplantation (n=90). Tumour tissue was investigated for p‐p70S6, phospho‐AKT, Ki‐67, Cyclin‐D1 and apoptosis, and staining results were correlated with clinicopathologically relevant parameters.Results: Overall, p‐p70S6 was detected in 24.5% (48/196) of HCCs. In the resection group, 26.4% (28/106) of HCC were positive and 22.2% (20/90) in the transplant group. p‐p70S6 was significantly associated with elevated Cyclin‐D1 immunoexpression and was correlated with decreased overall survival (P=0.011) in patients resected with a clear margin. In multivariate COX regression analysis, p‐p70S6 was identified as an independent prognostic parameter in patients resected with a clear margin. Rapamycin induced apoptosis and growth inhibition by G0/G1 cell cycle arrest in vitro. However, in HCC patients p‐p70S6 kinase was not associated with proliferation or apoptosis.Conclusions: Activation of p70S6 kinase indicates aggressive tumour behaviour in patients with clear margin‐resected HCC. Identification of p‐p70S6 kinase in HCC selects high‐risk patients who may benefit from drugs targeting the mTOR pathway.
Effects of silymarin on hepatitis C virus and haem oxygenase‐1 gene expression in human hepatoma cells
Authors: Bonifaz Vania , Shan Ying , Lambrecht Richard W. , Donohue Susan E. , Moschenross Darcy , Bonkovsky Herbert L. 
Published: February 2009

AbstractBackground/Aims:Hepatitis C virus (HCV) infection is a global medical problem. The current standard treatment of chronic hepatitis C (CHC), pegylated interferon plus ribavirin, is prolonged, expensive, has serious side effects and, at best, is only 50% effective. Silymarin (SI) is a natural antioxidant often used by patients with CHC, although its efficacy for decreasing HCV levels or ameliorating CHC remains uncertain. HCV infection is associated with increased hepatic oxidative stress, and one of the antioxidant enzymes that protect cells against this stress is haem oxygenase‐1 (HO‐1).Methods:We investigated effects of SI on HCV and HO‐1 gene expression in Huh‐7 cells, CNS3 and 9‐13 cells (the latter two stably expressing HCV‐proteins).Results:Silymarin significantly downregulated HCV core mRNA (by 20%–36%) and protein (by 30%–60%) in CNS3 cells. In contrast, SI did not decrease HCV NS5A mRNA or protein expression in 9‐13 cells. HO‐1 mRNA was upregulated (60%–400%) by SI in Huh‐7, CNS3 and 9‐13 cells, whereas BTB and CNC homology 1 and nuclear factor erythroid related factor 2 mRNA levels were not affected. The effect of SI to downregulate HCV core was not related to changes in the Janus‐activated tyrosine kinases–signal transducer and activators of transcription signalling pathway.Conclusions:Silymarin may be of benefit in CHC, although prospective, randomized, controlled trials are needed to be certain.
Alternative transporter pathways in patients with untreated early‐stage and late‐stage primary biliary cirrhosis
Authors: Takeyama Yasuaki , Uehara Yuko , Inomata Shinjiro , Morihara Daisuke , Nishizawa Shinya , Ueda Shu‐ichi , Matsumoto Teruo , Tanaka Takashi , Anan Akira , Nishimura Hirokatsu , Irie Makoto , Iwata Kaoru , Shakado Satoshi , Sohda Tetsuro , Sakisaka Shotaro 
Published: February 2009

AbstractBackground/Aims: The hepatic expression of bile acid transporters is altered in experimental cholestasis and it is unclear whether regulation exists in human cholestatic diseases. We investigated the expression of genes involved in bile acid detoxification, basolateral export and nuclear factor regulation in untreated primary biliary cirrhosis (PBC).Methods: Liver tissues were obtained from patients with early‐stage and late‐stage PBC. The hepatic expression levels of messenger RNAs were determined by the real‐time reverse transcription polymerase chain reaction.Results: The hepatic expression of multidrug‐resistance protein 4 messenger RNA was significantly upregulated in early‐stage and late‐stage PBC patients compared with controls. The hepatic expression of multidrug‐resistance protein 2 and multidrug‐resistance protein 3 messenger RNAs was significantly elevated only in early‐stage PBC patients. The hepatic expression levels of farnesoid X receptor, fetoprotein transcription factor and constitutive androstane receptor mRNAs were correlated with those of multidrug‐resistance protein 2, multidrug‐resistance protein 3 and multidrug‐resistance protein 4 respectively.Conclusions: The hepatic expression of multidrug‐resistance protein 4 was enhanced in patients with untreated PBC at all stages. However, the hepatic expression of multidrug‐resistance protein 2 and multidrug‐resistance protein 3 was enhanced only in early‐stage patients. The lack of upregulation of these proteins might contribute to the progression of PBC.
Over‐expression of glutamine synthetase in focal nodular hyperplasia: a novel easy diagnostic tool in surgical pathology
Authors: Bioulac‐Sage Paulette , Laumonier Hervé , Rullier Anne , Cubel Gaelle , Laurent Christophe , Zucman‐Rossi Jessica , Balabaud Charles 
Published: February 2009

AbstractBackground and Aims: Glutamine synthetase (GS) is a useful marker in tumour liver pathology, including hepatocellular adenomas and nodules in cirrhosis. We investigated the use of GS as a marker in various clinical situations, in which FNH diagnosis had been firmly established to determine its contribution to diagnosis.Methods: Seventy‐nine cases of resected FNH, all on normal (or occasionally steatotic) livers, were retrieved from our collection. The control group was composed of hepatocellular adenomas and well‐differentiated hepatocellular carcinoma. The following stains: H&E, Masson's trichrome, Gordon‐Sweet, PAS, perls and immunostains: CK7 and 19, and GS were carried out. FNH was diagnosed based on traditional pathological techniques. In case of uncertainty, particularly with hepatocellular adenoma, additional immunostainings including liver fatty acid‐binding protein, serum amyloid A and β‐catenin were performed.Results: Glutamine synthetase immunostaining was similar in all FNH cases. Positive GS staining of hepatocytic cytoplasms formed large areas, anastomosed in a ‘map‐like’ pattern, often surrounding hepatic veins, whereas GS was not expressed in hepatocytes close to fibrotic bands containing arteries and ductules. In comparison, hepatocellular adenoma staining was completely different, even in cases of fibrotic bands due to tumour remodelling related to necrosis or haemorrhage. In hepatocellular adenomas or well‐differentiated hepatocellular carcinoma presenting β‐catenin mutation, GS was positive but with a completely different pattern that appeared diffuse and not ‘map‐like’.Conclusion: Regardless of the FNH size or steatotic content, GS produced a similar and characteristic pattern and consequently represents a good marker for easily identifying resected FNH from other hepatocellular nodules.
Does cirrhosis affect quality of life in hepatitis C virus‐infected patients?
Authors: Hsu Priscilla C. , Krajden Mel , Yoshida Eric M. , Anderson Frank H. , Tomlinson George A. , Krahn Murray D. 
Published: February 2009

AbstractBackground: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and is associated with impairments in health‐related quality of life.Aims: To evaluate quality of life (QOL) in cirrhotic (compensated and decompensated) and non‐cirrhotic patients with chronic HCV infection, using preference‐based (utilities) and non‐preference‐based methods of evaluating QOL.Methods: In a tertiary care setting, 271 patients completed a self‐administered time trade‐off utility instrument, the Health Utility Index Mark 2 and Mark 3, and the Hepatitis Quality of Life Questionnaire Version 2. Mean QOL scores were compared across HCV disease stages and sociodemographical categories. We examined the association between QOL and disease stage using linear regression adjusting for age, education, marital status, log income and Charlson comorbidity scores. Mean utility scores were compared across disease stages using a propensity score method.Results: Mean utilities were lower than general population norms (0.81–0.92) and ranged from 0.62 to 0.82 in non‐cirrhotic patients (n=197), 0.56–0.84 in compensated cirrhotic patients (n=17) and 0.55–0.76 for decompensated cirrhotic patients (n=57). No significant association found was between disease stage and utility for current health status. Higher income, fewer comorbidities and living in a married or common‐law relationship were significantly associated with higher utilities and better QOL. No significant difference in utilities was found between disease stages using propensity score matching.Conclusions: Our study confirms that changes in HCV disease stage explain only small changes in QOL and suggests that factors such as underlying comorbidities, income and marital status have a greater effect on QOL than disease stage.
Adefovir dipivoxil is effective for the treatment of cirrhotic patients with lamivudine failure
Authors: Zoulim Fabien , Parvaz Parviz , Marcellin Patrick , Zarski Jean‐Pierre , Beaugrand Michel , Benhamou Yves , Bailly François , Maynard Marianne , Trepo Christian , Trylesinski Aldo , Monchecourt Françoise ,   the VIRESPA study group
Published: February 2009

AbstractBackground/Aims:Data on the efficacy of adefovir dipivoxil (ADV) in elderly and cirrhotic patients with lamivudine‐resistant (LAM‐R) chronic hepatitis B are scarce. This retrospective cohort study evaluated the safety and efficacy of ADV in this specific patient population.Methods:Sixty‐eight cirrhotic LAM‐R patients, of whom 19 (27.9%) were elderly (≥65 years of age) and nine had severe disease (two post‐orthotopic liver transplantation, four pre‐orthotopic liver transplantation and three decompensated), with hepatitis B virus (HBV) infection received ADV. Virological and biochemical responses to the addition of ADV were analysed.Results:At inclusion, all patients were receiving LAM; ADV was added. 75.4% of patients received a combination of LAM and ADV throughout this study for a median treatment duration of 12.6 months; the remainder received ADV with an overlap with LAM treatment for a median duration of 7.9 months. At the end of follow‐up, 41.2% of patients had undetectable HBV DNA (≤2000 copies/ml) with a median reduction of 3.4 log10 copies/ml. Time to reach undetectable HBV DNA was dependent on baseline alanine aminotransferase (ALT) levels and HBeAg status. Normalization of serum ALT levels was observed in 55.2% (32/58) of patients. In patients who were HBeAg positive at baseline, HBeAg loss and seroconversion occurred in 23% (9/39) and 10% (4/39) respectively. No resistance mutations and no significant side effects were observed during the study period.Conclusion:Adefovir dipivoxil provides effective and safe treatment in cirrhotic and elderly patients who failed LAM therapy.
Duplication of MER115 on chromosome 4 in patients with primary biliary cirrhosis
Authors: Xu Lizhe , Guo Linsheng , Shen Zhiwei , Loss George , Gish Robert , Wasilenko Shawn , Mason Andrew L. 
Published: February 2009

AbstractBackground: Primary biliary cirrhosis (PBC) is a complex disease with genetic and environmental influences. The disease is more prevalent in families with PBC and candidate gene case–control studies have linked PBC with DRB1*08 human leucocyte antigen class II alleles.Aims: The goal of this study was to characterize a MER115 intergenic region on chromosome 4 as a putative genetic variant associated with PBC.Methods/Results: This region was incidentally identified during investigations to discover candidate microbial agents using representational difference analysis (RDA) with liver samples from patients with PBC and primary sclerosing cholangitis (PSC). blast search analysis of all the RDA products from the PBC liver revealed genomic sequences, whereas Escherichia coli, mycoplasma and hepatitis B virus DNA were found in the PSC liver. We identified one of the PBC RDA products as an ancestral repeat, referred to as MER115. Southern blot analysis with the PBC product uncovered a restriction fragment length polymorphism in PBC patients' liver. Southern blot hybridization signal showed increased signal intensity in PBC vs. control patients' DNA (P<0.005) and slot blot hybridization studies confirmed a copy number variation of the MER115 in hepatic DNA of PBC vs. control patients (P=0.02).Conclusions: Further comparative genetic studies will be required to determine the extent of genomic duplication associated with MER115 and provide data on the possible copy number variants of genes close to this intergenic region in patients with PBC.
Hepatocyte expression of angiotensin II type 1 receptor is downregulated in advanced human liver fibrosis
Authors: Schulte Sigrid , Oidtmann Annika , Kociok Norbert , Demir Münevver , Odenthal Margarete , Drebber Uta , Dienes Hans‐Peter , Nierhoff Dirk , Goeser Tobias , Toex Ulrich , Steffen Hans‐Michael 
Published: February 2009

AbstractBackground: The renin–angiotensin system plays an important role in fibrosis. Angiotensin II regulates key steps in tissue remodelling processes through angiotensin II type 1 receptor (AT1R). In bile duct‐occluded rats, AT1R expression is significantly decreased in advanced liver fibrosis. Therefore, we studied the AT1R expression in human liver tissue during different stages of fibrosis caused by chronic hepatitis C.Methods: Liver biopsy specimens from 85 patients were analysed. Real‐time reverse transcription polymerase chain reaction was used to quantify AT1R mRNA. Immunohistochemical labelling of AT1R and double staining for AT1R, CD31, CD68, CD3 and fibulin‐2 were performed.Results: AT1R mRNA was significantly reduced in human liver tissue with end‐stage cirrhosis compared with early fibrosis. In liver cirrhosis, immunohistochemistry revealed a decreased expression of AT1R on hepatocytes, together with an increased staining intensity on myofibroblasts, vascular endothelium and bile duct epithelium.Conclusion: In conclusion, AT1R expression is downregulated in human liver cirrhosis specimens because of the reduced expression levels on hepatocytes. Therefore, antifibrogenic therapy with AT1R blockers may be most promising if initiated during early stages of fibrosis.
Determinants of transhepatic cholesterol flux and their relevance for gallstone formation
Authors: Zanlungo Silvana , Rigotti Attilio 
Published: February 2009

AbstractCholesterol available for bile secretion is controlled by a wide variety of proteins that mediate lipoprotein cholesterol uptake and cholesterol transport and metabolism in the liver. From a disease perspective, abnormalities in the transhepatic traffic of cholesterol from plasma into the bile may influence the risk of cholesterol gallstone formation. This review summarizes some recent progress in understanding the hepatic determinants of biliary cholesterol secretion and its potential pathogenic implications in cholesterol gallstone disease. This information together with new discoveries in this field may lead to improved risk evaluation, novel surrogate markers and earlier diagnosis, better preventive approaches and more effective pharmacological therapies for this prevalent human disease.
Mannitol facilitates neurotrophic factor up‐regulation and behavioural recovery in neonatal hypoxic‐ischaemic rats with human umbilical cord blood grafts
Authors: Yasuhara T. , Hara K. , Maki M. , Xu L. , Yu G. , Ali M. M. , Masuda T. , Yu S. J. , Bae E. K. , Hayashi T. , Matsukawa N. , Kaneko Y. , Kuzmin‐Nichols N. , Ellovitch S. , Cruz E. L. , Klasko S. K. , Sanberg C. D. , Sanberg P. R. , Borlongan C. V. 
Published: February 2009

AbstractWe recently demonstrated that blood–brain barrier permeabilization using mannitol enhances the therapeutic efficacy of systemically administered human umbilical cord blood (HUCB) by facilitating the entry of neurotrophic factors from the periphery into the adult stroke brain. Here, we examined whether the same blood–brain barrier manipulation approach increases the therapeutic effects of intravenously delivered HUCB in a neonatal hypoxic‐ischaemic (HI) injury model. Seven‐day‐old Sprague–Dawley rats were subjected to unilateral HI injury and then at day 7 after the insult, animals intravenously received vehicle alone, mannitol alone, HUCB cells (15k mononuclear fraction) alone or a combination of mannitol and HUCB cells. Behavioural tests at post‐transplantation days 7 and 14 showed that HI animals that received HUCB cells alone or when combined with mannitol were significantly less impaired in motor asymmetry and motor coordination compared with those that received vehicle alone or mannitol alone. Brain tissues from a separate animal cohort from the four treatment conditions were processed for enzyme‐linked immunosorbent assay at day 3 post‐transplantation, and revealed elevated levels of GDNF, NGF and BDNF in those that received HUCB cells alone or when combined with mannitol compared with those that received vehicle or mannitol alone, with the combined HUCB cells and mannitol exhibiting the most robust neurotropic factor up‐regulation. Histological assays revealed only sporadic detection of HUCB cells, suggesting that the trophic factor–mediated mechanism, rather than cell replacement per se, principally contributed to the behavioural improvement. These findings extend the utility of blood–brain barrier permeabilization in facilitating cell therapy for treating neonatal HI injury.
Differential regulation of connective tissue growth factor in renal cells by histone deacetylase inhibitors
Authors: Komorowsky Claudiu , Ocker Matthias , Goppelt‐Struebe Margarete 
Published: February 2009

AbstractRegulation of the profibrotic and angiogenesis modulating cytokine connective tissue growth factor (CTGF) occurs primarily at the transcriptional level. Therefore, we hypothesized that histone deacetylating enzymes (HDAC), which modulate the accessibility of transcriptionally active promoter regions, might play a role in the regulation of CTGF gene expression. We analyzed microvascular endothelial cells, which showed immunoreactivity for acetylated histone in kidney sections, and compared them with renal tubular epithelial cells. Treatment of cultured endothelial cells with different HDAC inhibitors up‐regulated CTGF mRNA and protein. Pre‐treatment with HDAC inhibitors facilitated induction of CTGF by transforming growth factor–beta (TGF‐β) or lysophosphatidic acid. Transcription factors of the FoxO family were involved in the up‐regulation of CTGF as shown at protein level and by reporter gene analyses. In tubular epithelial cells, up‐regulation of CTGF was only observed when these cells were cultured as subconfluent cells. Dense cells, which are more likely to resemble tubular cells in vivo, showed no up‐regulation upon treatment with HDAC inhibitors and were protected against CTGF induction by TGF‐β. Taken together, our data indicate that the effect of HDAC inhibitors on CTGF expression is largely cell dependent in non‐tumour cells. Different cell type–specific transcription factors seem to determine whether CTGF expression is reduced or increased in cells exposed to HDAC inhibitors.
Immune thrombocytopenic purpura: the treatment paradigm
Authors: Stasi Roberto 
Published: February 2009

AbstractImmune (idiopathic) thrombocytopenic purpura (ITP) is a heterogeneous disease with highly variable severity and an unpredictable response to therapy. This heterogeneity presents a range of problems to the clinician when deciding who should receive pharmacological treatment and when such interventions should be initiated. Treatment guidelines are available but, given the current small amount of data from research and randomized, controlled trials, the guidelines are largely based on expert opinion rather than on evidence. At the moment, it is only recommended that those patients with severe bleeding and/or extremely low platelet counts (<10 × 109/L) definitely require treatment. In all other patients the decision to treat must be made based on a careful evaluation of disease severity, patient characteristics, and the possibility of treatment‐related adverse events. This article describes a structured approach to the management of adults with ITP.