bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of genes putatively involved in the pathogenesis of diffuse large B‐cell lymphomas by integrative genomics
Authors: Oudejans Joost J. , van Wieringen Wessel N. , Smeets Serge J. , Tijssen Marianne , Vosse Sjoerd J. , Meijer Chris J. L. M. , Meijer Gerrit A. , van de Wiel Mark A. , Ylstra Bauke 
Published: December 2008

AbstractDiffuse large B‐cell lymphomas (DLBCL) are highly heterogeneous with regard to clinical presentation and outcome. DLBCL copy number aberrations have been identified previously, of which the deletion at 6q21‐24 was significantly associated with a highly favorable clinical response to chemotherapy. In this study, we aimed to identify genes implicated in this and other genomic regions with recurrent losses and/or gains. To identify implicated genes, we superimposed array comparative genomic hybridization (aCGH) data onto a microarray expression dataset of 42 clinically well‐characterized primary nodal DLBCL biopsies. We confirmed that loss of 6q21‐24 is significantly associated with a highly favorable clinical response to chemotherapy. Our approach identified 316 significant genes restricted to 32 chromosomal regions, including 24 genes identified at 6q21‐24. In an independent dataset, 18% of overexpressed genes in gained regions and 55% of down‐regulated genes in deleted regions were validated. In summary, using integrative genomics novel onco and tumor suppressor genes were identified in DLBCL that were not recognized by expression profiling alone. © 2008 Wiley‐Liss, Inc.
No genomic aberrations in Langerhans cell histiocytosis as assessed by diverse molecular technologies
Authors: da Costa Cristiana E. T. , Szuhai Karoly , van Eijk Ronald , Hoogeboom Manja , Sciot Raphael , Mertens Fredrik , Björgvinsdóttir Helga , Debiec‐Rychter Maria , de Krijger Ronald R. , Hogendoorn Pancras C. W. , Egeler R. Maarten , Annels Nicola E. 
Published: December 2008

AbstractThe etiology of Langerhans cell histiocytosis (LCH), a disease characterized by uncontrolled proliferation of Langerhans cells, is unknown. Although some believe that LCH is reactive, others support a neoplastic origin. We tested the hypothesis that LCH is neoplastic by investigating potential consistent chromosomal aberrations in LCH cells. We used multiparameter DNA flow cytometry to analyze the DNA ploidy LCH cells in 20 cases, performed karyotype analysis in 31 cases, array‐based comparative genomic hybridization (arrayCGH) and single nucleotide polymorphism (SNP) arrays with DNA from flow‐sorted CD1a‐positive and CD1a‐negative cells in 19 cases. Ploidy analysis revealed diploid DNA content in all cases. The karyotype of all patients analyzed was normal, excluding the presence of balanced translocations. ArrayCGH and SNP arrays did not show genome abnormalities. Despite positive TP53 protein immunohistochemical staining, sequencing of exon 5 to 8 of p53 gene showed no alterations in 7 cases. This study strongly suggests that gross chromosomal abnormalities do not cause LCH. Although we cannot exclude cryptic point mutations in as yet unidentified genes, this study of 72 LCH cases shows that LCH may be the result of restricted oligoclonal stimulation rather than unlimited neoplastic proliferation. © 2008 Wiley‐Liss, Inc.
Phosphorylation and lipid raft association of fibroblast growth factor receptor‐2 in oligodendrocytes
Authors: Bryant M. R. , Marta C. B. , Kim F. S. , Bansal R. 
Published: December 2008

AbstractFibroblast growth factors (FGFs) and their receptors (FGFRs) initiate diverse cellular responses that contribute to the regulation of oligodendrocyte (OL) function. To understand the mechanisms by which FGFRs elicit these cellular responses, we investigated the phosphorylation of signal transduction proteins and the role of cholesterol‐glycosphingolipid‐enriched “lipid raft” microdomains in differentiated OLs. Surprisingly, we found that the most abundant tyrosine‐phosphorylated protein in OLs was the 120‐kd isoform of FGFR2 and that it was phosphorylated even in the absence of FGF2, suggesting a potential ligand‐independent function for this receptor. Furthermore, FGFR2, but not FGFR1, was associated with lipid raft microdomains in OLs and myelin (but not in astrocytes). This provides the first evidence for the association of FGFR with TX‐100‐insoluble lipid raft fractions. FGFR2 phosphorylated the key downstream target, FRS2 in OLs. Raft disruption resulted in loss of phosphorylated FRS2 from lipid rafts, coupled with the loss of Akt but not of Mek or Erk phosphorylation. This suggests that FGFR2‐FRS2 signaling in lipid rafts operates via the PI3‐Kinase/Akt pathway rather than the Ras/Mek/Erk pathway, emphasizing the importance of microenvironments within the cell membrane. Also present in lipid rafts in OLs and myelin, but not in astrocytes, was a novel 52‐kd isoform of FGFR2 that lacked the extracellular ligand‐binding region. These results demonstrate that FGFR2 in OLs and myelin possess unique characteristics that are specific both to receptor type and to OLs and provide a novel mechanism to elicit distinct cellular responses that mediate both FGF‐dependent and ‐independent functions. © 2008 Wiley‐Liss, Inc.
Hepatitis B virus surface antigen levels: A guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B # †
Authors: Brunetto Maurizia Rossana , Moriconi Francesco , Bonino Ferruccio , Lau George K. K. , Farci Patrizia , Yurdaydin Cihan , Piratvisuth Teerha , Luo Kangxian , Wang Yuming , Hadziyannis Stephanos , Wolf Eva , McCloud Philip , Batrla Richard , Marcellin Patrick 
Published: December 2008

Abstract
We investigated the relationship between hepatitis B virus surface antigen (HBsAg) serum level decline and posttreatment response in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B from a large multinational study of pegylated interferon alfa-2a (peginterferon alfa-2a), with or without lamivudine, versus lamivudine alone. Serum HBsAg was quantified using the Architect assay (Abbott Diagnostics) at pretreatment, end of treatment (week 48), and 6 months after the end of treatment (week 72) in sera from 386 of the 537 patients who participated in the multinational study (peginterferon alfa-2a, 127; peginterferon alfa-2a plus lamivudine, 137; lamivudine monotherapy, 122). Pretreatment HBsAg levels varied according to genotype, with the highest levels present in patients infected with genotypes A (median, 4.11 log10 IU/mL) and D (median, 3.85 log10 IU/mL). Significant on-treatment decline in HBsAg was observed during treatment with peginterferon alfa-2a (alone or combined with lamivudine; mean decline at week 48, −0.71 and −0.67 log10 IU/mL, respectively, P < 0.001), but not during treatment with lamivudine alone (−0.02 log10 IU/mL). Significantly more patients treated with peginterferon alfa-2a (21%) or peginterferon alfa-2a plus lamivudine (17%) achieved HBsAg levels <100 IU/mL at the end of treatment compared with lamivudine (1%) (both P < 0.001 versus lamivudine). End-of-treatment HBsAg level correlated strongly with HBV DNA suppression to ≤400 copies/mL 6 months posttreatment. An HBsAg level <10 IU/mL at week 48 and on-treatment decline >1 log10 IU/mL were significantly associated with sustained HBsAg clearance 3 years after treatment (both P < 0.0001). Conclusion: On-treatment quantification of HBsAg in patients with HBeAg-negative chronic hepatitis B treated with peginterferon alfa-2a may help identify those likely to be cured by this therapy and optimize treatment strategies. (Hepatology 2009;49:1141–1150.)
Natural killer T cells regulate the homing of chemokine CXC receptor 3-positive regulatory T cells to the liver in mice #
Authors: Santodomingo-Garzon Tania , Han Jinglan , Le Tai , Yang Yang , Swain Mark G. 
Published: December 2008

Abstract
Natural killer T (NKT) cells and regulatory T cells (Tregs) are both found within the liver and are known to exhibit immune regulatory functions. Hepatic NKT cells are activated early during inflammatory responses and release cytokines, including interferon gamma (IFN-γ), which we speculated could regulate Treg recruitment to the liver. To examine this, we treated C57BL/6 mice with a specific NKT cell activating ligand α galactosyl-C18-ceramide (αGal-C18-Cer) and examined the hepatic recruitment of Tregs. We found a time-dependant increase in the hepatic recruitment of Tregs after NKT cell activation, which was absent in NKT cell–deficient mice. Most recruited Tregs expressed interleukin (IL) 10, and to a lesser extent transforming growth factor beta (TGF-β). Because IFN-γ induces the production of chemokine (C-X-C motif) ligand 10 (CXCL10), and Tregs can express the cognate receptor for CXCL10 (that is, CXCR3), we considered that CXCL10 might mediate the hepatic recruitment of Tregs after NKT cell activation. Hepatic CXCL10 levels were markedly increased after αGal-C18-Cer administration in wild-type but not in NKT cell–deficient mice. Moreover, approximately 50% of Tregs recruited to the liver after αGal-C18-Cer administration expressed CXCR3 and CXCR3+ Treg recruitment into the liver was significantly inhibited in IFN-γ KO mice, and after CXCL10 neutralization. In addition, prevention of CXCR3+ Treg recruitment into the liver enhanced inflammatory effector cell recruitment into the liver after αGal-C18-Cer treatment. Conclusion: These results show that activated NKT cells can induce the hepatic recruitment of Tregs through a cytokine-to-chemokine pathway, which could be relevant in the development of chemokine blocking or NKT cell activating strategies to treat liver diseases. (Hepatology 2009.)
Detection of novel biomarkers of liver cirrhosis by proteomic analysis #
Authors: Mölleken Christian , Sitek Barbara , Henkel Corinna , Poschmann Gereon , Sipos Bence , Wiese Sebastian , Warscheid Bettina , Broelsch Christoph , Reiser Markus , Friedman Scott L. , Tornφe Ida , Schlosser Anders , Klöppel Günter , Schmiegel Wolff , Meyer Helmut E. , Holmskov Uffe , Stühler Kai 
Published: December 2008

Abstract
Hepatic cirrhosis is a life-threatening disease arising from different chronic liver disorders. One major cause for hepatic cirrhosis is chronic hepatitis C. Chronic hepatitis C is characterized by a highly variable clinical course, with at least 20% developing liver cirrhosis within 40 years. Only liver biopsy allows a reliable evaluation of the course of hepatitis C by grading inflammation and staging fibrosis, and thus serum biomarkers for hepatic fibrosis with high sensitivity and specificity are needed. To identify new candidate biomarkers for hepatic fibrosis, we performed a proteomic approach of microdissected cirrhotic septa and liver parenchyma cells. In cirrhotic septa, we detected an increasing expression of cell structure associated proteins, including actin, prolyl 4-hydroxylase, tropomyosin, calponin, transgelin, and human microfibril–associated protein 4 (MFAP-4). Tropomyosin, calponin, and transgelin reflect a contribution of activated stellate cells/myofibroblasts to chronic liver injury. The expression of tropomyosin, transgelin, and MFAP-4, an extracellular matrix associated protein, were further evaluated by immunohistochemistry. Tropomyosin and MFAP-4 demonstrated high serum levels in patients with hepatic cirrhosis of different causes. Conclusion: A quantitative analysis of MFAP-4 serum levels in a large number of patients showed MFAP-4 as novel candidate biomarker with high diagnostic accuracy for prediction of nondiseased liver versus cirrhosis [area under receiver operating characteristic curve (AUC) = 0.97, P < 0.0001] as well as stage 0 versus stage 4 fibrosis (AUC = 0.84, P < 0.0001), and stages 0 to 3 versus stage 4 fibrosis (AUC = 0.76, P < 0.0001). (Hepatology 2009.)
Association study between glutathione S‐transferase GST‐M1, GST‐T1, and GST‐P1 polymorphisms and tardive dyskinesia
Authors: Kang Seung‐Gul , Lee Heon‐Jeong , Choi Jung‐Eun , An Hyonggin , Rhee MinKyu , Kim Leen 
Published: December 2008

AbstractObjectivesData from several studies suggest that oxidative stress may play a role in the pathophysiology of tardive dyskinesia (TD). Glutathione S‐transferase (GST) enzymes play important roles in protecting cells against oxidative stress. In the present study, we investigated the hypothesis that polymorphisms in genes for these detoxifying enzymes can influence susceptibility to TD in patients with schizophrenia.MethodsThe GST‐M1, GST‐T1, and GST‐P1 loci were analyzed by polymerase chain reaction (PCR)‐based methods in 83 schizophrenic patients with TD and 126 schizophrenic without TD who were matched for antipsychotic drug exposure and other relevant variables. The multifactor dimensionality reduction (MDR) approach was used to analyze gene–gene interactions.ResultsThere were no significant differences in the distributions of the GST‐M1, GST‐T1, and GST‐P1 genotypes between the TD and non‐TD groups (p > 0.05). However, in comparison of the severity of TD among genotypes using Poisson regression showed that Ile/Ile genotype of GST‐P1 had higher AIMS score compared to Ile/Val + Val/Val genotypes (X2 = 7.13, p = 0.008). MDR analysis did not show a significant interaction between the three GST gene variants and susceptibility to TD (p > 0.05).ConclusionsThese results suggest that GST gene polymorphisms do not confer increased susceptibility to TD in patients with schizophrenia but TD severity might be related with GST‐P1 variants. Copyright © 2008 John Wiley & Sons, Ltd.
The t‐PA‐encapsulated PLGA nanoparticles shelled with CS or CS‐GRGD alter both permeation through and dissolving patterns of blood clots compared with t‐PA solution: An in vitro thrombolysis study
Authors: Wang Shoei‐Shen , Chou Nai‐Kuan , Chung Tze‐Wen 
Published: December 2008

AbstractAccelerated thrombolysis by pressure‐driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t‐PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS‐GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t‐PA encapsulated in NPs. The t‐PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS‐GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t‐PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS‐GRGD NPs revealed extremely rough surfaces to a depth of 100 μm, indicating that a cross‐permeation direction of clot lysis occurred, while those dissolved with t‐PA solution showed slightly rough surfaces to a depth of 12 μm. Permeation through and clot dissolution patterns of thrombolysis with t‐PA encapsulated in NPs shelled with CS or CS‐GRGD distinctly differed from those dissolved with t‐PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Investigations into the development of catalytic activity in anti‐acetylcholinesterase idiotypic and anti‐idiotypic antibodies
Authors: Johnson Glynis , Moore Samuel W. 
Published: December 2008

AbstractWe have previously described anti‐acetylcholinesterase antibodies that display acetylcholinesterase‐like catalytic activity. No evidence of contaminating enzymes was found, and the antibodies are kinetically and apparently structurally distinct from both acetylcholinesterase (AChE) and butyrylcholinesterase. We have also mimicked the antibody catalytic sites in anti‐anti‐idiotypic (Ab3) antibodies. Independently from us, similar acetylcholinesterase‐like antibodies have been raised as anti‐idiotypic (Ab2) antibodies against a non‐catalytic anti‐acetylcholinesterase antibody, AE‐2. In this paper, we describe an epitope analysis, using synthetic peptides in ELISA and competition ELISA, and a peptide array, of five catalytic anti‐acetylcholinesterase antibodies (Ab1s), three catalytic Ab3s, as well as antibody AE‐2 and a non‐catalytic Ab2. The catalytic Ab1s and Ab3s recognized three Pro‐ and Gly‐containing sequences (40PPMGPRRFL,78PGFEGTE, and258PPGGTGGNDTELVAC) on the AChE surface. As these sequences do not adjoin in the AChE structure, recognition would appear to be due to cross‐reaction. This was confirmed by the observation that the sequences superimpose structurally. The non‐catalytic antibodies, AE‐2 and the Ab2, recognized AChE's peripheral anionic site (PAS), in particular, the sequence70YQYVD, which contains two of the site's residues. The crystal structure of the AChE tetramer (Bourneet al., 1999) shows direct interaction and high complementarity between the257CPPGGTGGNDTELVAC sequence and the PAS. Antibodies recognizing the sequence and the PAS may, in turn, be complementary; this may account for the apparent paradox of catalytic development in both Ab1s and Ab2s. The PAS binds, but does not hydrolyze, substrate. The catalytic Ab1s, therefore, recognize a site that may function as a substrate analog, and this, together with the presence of an Arg‐Glu salt bridge in the epitope, suggests mechanisms whereby catalytic activity may have developed. In conclusion, the development of AChE‐like catalytic activity in anti‐AChE Ab1s and Ab2s appears to be the result of a combination of structural complementarity to a substrate‐binding site, charge complementarity to a salt bridge, and specific structural peculiarities of the AChE molecule. Copyright © 2008 John Wiley & Sons, Ltd.
Non‐stationary frequency analysis of extreme daily rainfall in Sao Paulo, Brazil
Authors: Sugahara Shigetoshi , da Rocha Rosmeri Porfírio , Silveira Reinaldo 
Published: December 2008

AbstractThis work is an assessment of frequency of extreme values (EVs) of daily rainfall in the city of Sao Paulo, Brazil, over the period 1933–2005, based on the peaks‐over‐threshold (POT) and Generalized Pareto Distribution (GPD) approach. Usually, a GPD model is fitted to a sample of POT values selected with a constant threshold. However, in this work we use time‐dependent thresholds, composed of relatively largepquantiles (for examplepof 0.97) of daily rainfall amounts computed from all available data. Samples of POT values were extracted with several values ofp. Four different GPD models (GPD‐1, GPD‐2, GPD‐3, and GDP‐4) were fitted to each one of these samples by the maximum likelihood (ML) method. The shape parameter was assumed constant for the four models, but time‐varying covariates were incorporated into scale parameter of GPD‐2, GPD‐3, and GPD‐4, describing annual cycle in GPD‐2, linear trend in GPD‐3, and both annual cycle and linear trend in GPD‐4. The GPD‐1 with constant scale and shape parameters is the simplest model. For identification of the best model among the four models we used rescaled Akaike Information Criterion (AIC) with second‐order bias correction. This criterion isolates GPD‐3 as the best model, i.e. the one with positive linear trend in the scale parameter. The slope of this trend is significant compared to the null hypothesis of no trend, for about 98% confidence level. The non‐parametric Mann–Kendall test also showed presence of positive trend in the annual frequency of excess over high thresholds, withp‐value being virtually zero. Therefore, there is strong evidence that high quantiles of daily rainfall in the city of Sao Paulo have been increasing in magnitude and frequency over time. For example, 0.99 quantiles of daily rainfall amount have increased by about 40 mm between 1933 and 2005. Copyright © 2008 Royal Meteorological Society
Spatio‐temporal rainfall patterns in Southern South America
Authors: Aravena Juan‐Carlos , Luckman Brian H. 
Published: December 2008

AbstractThe dominant spatial and temporal patterns of a network of 23 homogenous instrumental rainfall records of Southern South America were analysed and used to define four regional annual precipitation series: (1) Northwestern Patagonia (1950–2000) with nine stations from both side of the Andes between 41 and 44°S; (2) Central Patagonia (1950–2000) with five Chilean stations between 45 and 47°S; (3) Patagonian plains–Atlantic (1961–2000) with five Argentinean stations spread between 43 and 50°S and from the eastern foothills of the Andes to the Atlantic coast and (4) Southern Patagonia (1950–2000) with four stations east of the Andes, near the Strait of Magellan between 51 and 53°S. Unique patterns were also identified for two of the southernmost stations in Ushuaia and Evangelistas (EVA). Time series analysis of these regional patterns shows marked decadal variability for Northwestern and Central Patagonia, 3–7 years oscillations for the Patagonian plains–Atlantic region and a strong biannual oscillation mode for Southern Patagonia. Regional annual rainfall appears to be strongly influenced by Antarctic circulation modes (Antarctic Oscillation Index), whereas the El Niño‐Southern Oscillation (ENSO) influence on rainfall variability is less evident. Highly significant correlation of precipitation on the west coast of Patagonia with the pressure gradient between the subtropical eastern Pacific and the high‐latitude south eastern Pacific is confirmed. Copyright © 2008 Royal Meteorological Society
Vapor‐Based Polymer Gradients
Authors: Elkasabi Yaseen , Lahann Joerg 
Published: December 2008

AbstractChemical vapor deposition (CVD) co‐polymerization was used to fabricate polymer coatings, which comprise of reactive surface composition gradients. Two functionalized derivatives of [2.2]paracyclophane were fed into a two‐source CVD system at a 180 ° angle, then copolymerized and deposited as a polymer gradient. Infrared and X‐ray photoelectron spectroscopy (XPS) confirmed the compositional changes within the bulk polymer and at the surface. By manipulating process parameters, gradients of tailored compositional slope can be deposited on a wide range of substrates. We also were able to selectively immobilize fluorescence‐labeled ligands onto the reactive polymer gradients, making CVD‐based gradient surfaces a flexible platform for fabricating biomolecular substrates.magnified image
Movement disturbances in the differential diagnosis of Creutzfeldt‐Jakob disease
Authors: Edler Jan , Mollenhauer Brit , Heinemann Uta , Varges Daniela , Werner Carola , Zerr Inga , Schulz‐Schaeffer Walter J. 
Published: December 2008

AbstractMovement disturbances are common in dementia disorders and are a central feature of the clinical classification criteria of Creutzfeldt‐Jakob disease (CJD). Polymorphism at codon 129 of the prion protein gene is known to determine the clinical picture of CJD. The frequency and characteristics of movement disturbances in other dementing disorders, such as Alzheimer's disease (AD), is barely known and leads to misdiagnoses. We investigated the occurrence and characteristics of movement disturbances in 143 patients neuropathologically confirmed with CJD (n = 100), AD (n = 29), dementia with Lewy bodies (DLB) (n = 7), or other diagnoses (n = 7). All patients had been referred with the differential diagnosis of prion disease. Ataxia and dysmetria were significantly more frequent in CJD than in AD or DLB patients, whereas hypokinesia was up to five times more frequent in AD or DLB (P < 0.05). Using an ordered logistic regression to identify constellations of movement disturbances, the diagnosis of CJD was likely in patients presenting ataxia but not hypokinesia. The reverse situation was statistically associated with AD. Ataxia and cogwheel rigidity were associated with valine‐homozygosity and akinesia with methionine‐homozygosity in the CJD patients. Our results indicate that the careful assessment of movement disturbances may be helpful in the differential diagnosis of Creutzfeldt‐Jakob disease. © 2008 Movement Disorder Society