bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caffeine Inhibits Human Immunodeficiency Virus Type 1 Transduction of Nondividing Cells
Authors: Daniel René , Marusich Elena , Argyris Elias , Zhao Richard Y. , Skalka Anna Marie , Pomerantz Roger J. 
Published: January 2005

ABSTRACT
Caffeine is an efficient inhibitor of DNA repair and DNA damage-activated checkpoints. We have shown recently that caffeine inhibits retroviral transduction of dividing cells, most likely by blocking postintegration repair. This effect may be mediated at least in part by a cellular target of caffeine, the ataxia telangiectasia-mutated and Rad3-related (ATR) kinase. In this study, we present evidence that caffeine also inhibits efficient transduction of nondividing cells. We observed reduced transduction in caffeine-treated growth-arrested cells as well as caffeine-treated terminally differentiated human neurons and macrophages. Furthermore, this deficiency was observed with a human immunodeficiency virus type 1 (HIV-1) vector lacking Vpr, indicating that the effect is independent of the presence of this viral protein in the infecting virion. Finally, we show that HIV-1 transduction of nocodazole-arrested cells is reduced in cells that express an ATR dominant-negative protein (kinase-dead ATR [ATRkd]) and that the residual transduction of ATRkd-expressing cells is relatively resistant to caffeine. Taken together, these data suggest that the effect(s) of caffeine on HIV-1 transduction is mediated at least partly by the inhibition of the ATR pathway but is not dependent on the caffeine-mediated inhibition of cell cycle checkpoints.
Identification of a Movement Protein of Rice Yellow Stunt Rhabdovirus
Authors: Huang Yan-Wei , Geng Yun-Feng , Ying Xiao-Bao , Chen Xiao-Ying , Fang Rong-Xiang 
Published: January 2005

ABSTRACTRice yellow stunt rhabdovirus(RYSV) encodes seven genes in its negative-sense RNA genome in the order 3′-N-P-3-M-G-6-L-5′. The existence of gene 3 in the RYSV genome and an analogous gene(s) of other plant rhabdoviruses positioned between the P and M genes constitutes a unique feature for plant rhabdoviruses that is distinct from animal-infecting rhabdoviruses in which the P and M genes are directly linked. However, little is known about the function of these extra plant rhabdovirus genes. Here we provide evidence showing that the protein product encoded by gene 3 of RYSV, P3, possesses several properties related to a viral cell-to-cell movement protein (MP). Analyses of the primary and secondary protein structures suggested that RYSV P3 is a member of the “30K” superfamily of viral MPs. Biolistic bombardment transcomplementation experiments demonstrated that RYSV P3 can support the intercellular movement of a movement-deficient potexvirus mutant inNicotiana benthamianaleaves. In addition, Northwestern blot analysis indicated that the RYSV P3 protein can bind single-stranded RNA in vitro, a common feature of viral MPs. Finally, glutathioneS- transferase pull-down assays revealed a specific interaction between the RYSV P3 protein and the N protein which is a main component of the ribonucleocapsid, a subviral structure believed to be involved in the intercellular movement of plant rhabdoviruses. Together, these data suggest that RYSV P3 is likely a MP of RYSV, thus representing the first example of characterized MPs for plant rhabdoviruses.
Norovirus Proteinase-Polymerase and Polymerase Are Both Active Forms of RNA-Dependent RNA Polymerase
Authors: Belliot Gaël , Sosnovtsev Stanislav V. , Chang Kyeong-Ok , Babu Vijay , Uche Uzo , Arnold Jamie J. , Cameron Craig E. , Green Kim Y. 
Published: January 2005

ABSTRACT

In vitro mapping studies of the MD145 norovirus (
Caliciviridae
) ORF1 polyprotein identified two stable cleavage products containing the viral RNA-dependent RNA polymerase (RdRp) domains: ProPol (a precursor comprised of both the proteinase and polymerase) and Pol (the mature polymerase). The goal of this study was to identify the active form (or forms) of the norovirus polymerase. The recombinant ProPol (expressed as Pro
−
Pol with an inactivated proteinase domain to prevent autocleavage) and recombinant Pol were purified after synthesis in bacteria and shown to be active RdRp enzymes. In addition, the mutant His-E1189A-ProPol protein (with active proteinase but with the natural ProPol cleavage site blocked) was active as an RdRp, confirming that the norovirus ProPol precursor could possess two enzymatic activities simultaneously. The effects of several UTP analogs on the RdRp activity of the norovirus and feline calicivirus Pro
−
Pol enzymes were compared and found to be similar. Our data suggest that the norovirus ProPol is a bifunctional enzyme during virus replication. The availability of this recombinant ProPol enzyme might prove useful in the development of antiviral drugs for control of the noroviruses associated with acute gastroenteritis.
Prognostic value of Bax, Bcl-2, p53, and TUNEL staining in patients with radically resected ampullary carcinoma
Authors: Santini D , Tonini G , Vecchio F M , Borzomati D , Vincenzi B , Valeri S , Antinori A , Castri F , Coppola R , Magistrelli P , Nuzzo G , Picciocchi A 
Published: January 2005

Background:There is a lack of data in the literature concerning the identification of potential prognostic factors in ampullary adenocarcinoma.Aims:To examine the prognostic significance of Bax, Bcl-2, and p53 protein expression and the apoptotic index in a large cohort of uniformly treated patients with radically resected ampullary cancer.Methods:All patients with a pathological diagnosis of ampullary cancer and radical resection were evaluated. Expression analysis for p53, Bax, and Bcl-2 was performed by immunohistochemistry. Apoptotic cells were identified by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL).Results:Thirty nine tumour specimens from patients with radically resected ampullary adenocarcinoma were studied. A positive significant correlation between Bax and p53 expression was found by rank correlation matrix (p < 0.001). A trend towards a positive correlation was found between the apoptotic index and p53 expression (p  =  0.059). By univariate analysis, overall survival was influenced by Bax expression, p53 expression, and TUNEL staining (p  =  0.001, p  =  0.01, and p  =  0.03, respectively). Bcl-2 expression did not influence overall survival in these patients (p  =  0.55). By multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was Bax expression (p  =  0.020).Conclusions:These results provide evidence that apoptosis may be an important prognostic factor in patients with radically resected ampullary cancer. This study is the first to assess the clinical usefulness of Bax expression in radically resected ampullary cancer.
Clinicopathological study of cellular proliferation and invasion in gliomatosis cerebri: important role of neural cell adhesion molecule L1 in tumour invasion
Authors: Suzuki T , Izumoto S , Fujimoto Y , Maruno M , Ito Y , Yoshimine T 
Published: January 2005

Background/Aims:In patients with gliomatosis cerebri (GC), glial fibrillary acidic protein (GFAP) positive cells invade the entire brain, particularly the white matter. Because the nosological definition and histogenesis of GC remain controversial, the morphology and immunohistochemical staining patterns of neoplastic GC cells were compared with those of other gliomas.Methods:An immunohistochemical analysis of neoplastic cells from four patients with GC and 20 with astrocytic tumours using antibodies against Ki-67, GFAP, and L1, the last of which is a neural cell adhesion molecule putatively related to glioma invasion.Results:GC tumour cells can be divided into two types, those mainly composed of strongly GFAP and L1 positive gemistocytic cells, the other composed of small, GFAP and L1 negative spindle shaped cells. The two types did not differ with respect to Ki-67 positivity. Cells from patients with other gliomas were positive for GFAP but concurrent L1 expression was negative or weakly positive.Conclusion:The strong expression of L1 in patients with GC and its poor expression in the 20 patients with other types of glioma, including those with GFAP positive gemistocytic astrocytomas, suggest that L1 expression may play a role in the histogenesis of GC.
Imprinting, expression, and localisation of DLK1 in Wilms tumours
Authors: Fukuzawa R , Heathcott R W , Morison I M , Reeve A E 
Published: January 2005

Background:Loss of imprinting (LOI) of the H19/IGF2 domain is a common feature of Wilms tumour. The GTL2/DLK1 domain is also imprinted and is structurally similar to H19/IGF2. The question arises as to whether DLK1 also undergoes LOI in Wilms tumour, or whether the LOI mechanism is restricted to the H19/IGF2 domain.Aim:To investigate the imprinting status of DLK1 in Wilms tumours with IGF2 LOI. The cellular localisation of DLK1 in the tumours was also examined.Methods:DLK1 expression was measured by quantitative real time polymerase chain reaction (Q-PCR) in 30 Wilms tumours that had previously been classified according to whether they had IGF2 LOI, WT1 mutations, or 11p15.5 loss of heterozygosity. Allele specific expression of DLK1 was examined by direct sequencing using a DLK1 exon 5 polymorphism (rs1802710). Immunohistochemical analysis of DLK1 was performed on 13 tumours and two intralobar nephrogenic rests, in addition to two fetal kidneys and one fetal skeletal muscle sample.Results:Ten of 30 tumours were heterozygous for rs1802710 and all tumours showed retention of imprinting of DLK1. Moderate to high expression of DLK1 was detected by Q-PCR in nine of 13 tumours with myogenic differentiation. Immunohistochemical expression of DLK1 was detected in the myogenic elements.Conclusion:LOI does not occur at the GTL2/DLK1 domain in Wilms tumour. This finding suggests that LOI at 11p15.5 does not reflect non-specific disruption of a shared imprinting mechanism. DLK1 expression in Wilms tumour might reflect the presence of myogenic differentiation, rather than an alteration of its imprinting status.
Apolipoprotein E Promotes the Regression of Atherosclerosis Independently of Lowering Plasma Cholesterol Levels
Authors: Raffai Robert L. , Loeb Samuel M. , Weisgraber Karl H. 
Published: January 2005

Objective—The mechanisms by which apolipoprotein E (apoE) can promote the regression of atherosclerosis are not well understood. This study examined whether apoE can promote atherosclerosis regression independently of lowering plasma cholesterol levels.Methods and Results—We studied hypomorphic apoE mice (Apoeh/h), which express an apoE4-like form of mouse apoE at ≈2% to 5% of normal levels in plasma and are normolipidemic. After 18 weeks of diet-induced hypercholesterolemia, which resulted in advanced aortic atherosclerotic lesions composed of a lipid-rich layer of foam cells covering a fibrotic core, 2 groups of mice were fed a chow diet for 16 weeks. One group continued to express low levels of apoE; the other was induced to express physiological levels of plasma apoE by Cre-mediated recombination of the hypomorphicApoeallele. In both groups, plasma cholesterol levels fell rapidly to similar levels, and histological analysis at 16 weeks revealed elimination of the foam-cell layer. However, physiological levels of plasma apoE also enhanced the removal of neutral lipids from the fibrotic cores.Conclusion—These findings demonstrate for the first time that apolipoprotein E promotes the regression of atherosclerosis independently of lowering plasma cholesterol levels.
Mineralogical and geochemical characteristics (major, minor, trace elements and REE) of detrital and authigenic clay minerals in a Cenozoic sequence from Ross Sea, Antarctica
Authors: Setti M. , Marinoni L. , López-Galindo A. 
Published: January 2005

AbstractThe mineralogy and geochemistry of the clay fraction of Victoria Land Basin (Ross Sea, Antarctica) sediments was investigated, to determine the origin of clay minerals and the features of authigenic smectite. The investigated core (CRP-3) is ~800 m long, mostly of Oligocene age. The clay fraction of the upper sequence consists of mica, chlorite and detrital smectite, while that of the central and lower part is largely made up of authigenic smectite. Authigenic smectites are ditrioctahedral, with a composition close to saponite, while detrital smectites such as Al-Fe beidellites are dioctahedral. Authigenic smectites have no illite mixed layers, show a higher degree of crystallization, higher MgO, Fe2O3, V, Cr, Co, Ni and Sc contents and lower SiO2, Al2O3, K2O, TiO2, Ba, Rb and Zr contents with respect to detrital clay minerals, and a clear depletion of LREE with respect to HREE. Authigenic smectite formed from the alteration of volcanic materials and clay minerals.
Identification of novel prognostic markers in cervical intraepithelial neoplasia using LDMAS (LOH Data Management and Analysis Software)
Authors: Hamoudi Rifat A , El-Hamidi Amina , Du Ming-Qing 
Published: January 2005

Abstract
Background
Detection of Loss of Heterozygosity (LOH) is one of the most common molecular applications in the study of human diseases, in particular cancer. The technique is commonly used to examine whether a known tumour suppressor gene is inactivated or to map unknown tumour suppressor gene(s). However, with the increasing number of samples analysed using different software, no tool is currently available to integrate and facilitate the extensive and efficient data retrieval and analyses, such as correlation of LOH data with various clinical data sets.

Results
An algorithm to identify prognostic disease markers is devised and implemented as novel software called LDMAS. LDMAS is a software suite designed for data retrieval, management and integrated analysis of the clinico-pathological data and molecular results from independent databases. LDMAS is used in stratification of disease stages according to clinical stage or histological features and correlation of various clinico-pathological features with molecular findings to obtain relevant prognostic markers such as those used in predicting the outcome of cervical intraepithelial neoplasia (CIN). This approach lead to the identification of novel prognostic cervical cancer markers and extraction of useful clinical information such as correlation of Human Papilloma Virus (HPV) status with CIN lesions.

Conclusions
A novel software called LDMAS is implemented and used to extract and identify prognostic disease markers. The software is used to successfully identify 4 novel prognostic markers that can be used to predict the outcome of CIN. LDMAS provides an essential platform for the extraction of useful information from large amount of data generated by LOH studies. LDMAS provides three unique and novel features for LOH analysis : (1) automatic extraction of relevant data from patient records and reports (2) correlation of LOH data with clinico-pathological data and (3) storage of complex data in flexible format. The first feature automates the creation of database of clinically relevant information from huge amount of data, the second feature extracts useful biomedical information such as prognostic markers in CIN and the third feature simplifies the statistical analyses of the data and allows non-statisticians to carry out the analysis. Additionally, LDMAS can be used to extract clinically useful markers from other diseases and interface to high throughput genotyping analysis software such as GDAS used to generate LOH data from Affymetrix® GeneChip Mapping arrays.
Assessing stability and change of four performance measures: a longitudinal study evaluating outcome following total hip and knee arthroplasty
Authors: Kennedy Deborah M , Stratford Paul W , Wessel Jean , Gollish Jeffrey D , Penney Dianne 
Published: January 2005

Abstract
Background
Physical performance measures play an important role in the measurement of outcome in patients undergoing hip and knee arthroplasty. However, many of the commonly used measures lack information on their psychometric properties in this population. The purposes of this study were to examine the reliability and sensitivity to change of the six minute walk test (6MWT), timed up and go test (TUG), stair measure (ST), and a fast self-paced walk test (SPWT) in patients with hip or knee osteoarthritis (OA) who subsequently underwent total joint arthroplasty.

Methods
A sample of convenience of 150 eligible patients, part of an ongoing, larger observational study, was selected. This included 69 subjects who had a diagnosis of hip OA and 81 diagnosed with knee OA with an overall mean age of 63.7 ± 10.7 years. Test-retest reliability, using Shrout and Fleiss Type 2,1 intraclass correlations (ICCs), was assessed preoperatively in a sub-sample of 21 patients at 3 time points during the waiting period prior to surgery. Error associated with the measures' scores and the minimal detectable change at the 90% confidence level was determined. A construct validation process was applied to evaluate the measures' abilities to detect deterioration and improvement at two different time points post-operatively. The standardized response mean (SRM) was used to quantify change for all measures for the two change intervals. Bootstrapping was used to estimate the 95% confidence intervals (CI) for the SRMs.

Results
The ICCs (95% CI) were as follows: 6MWT 0.94 (0.88,0.98), TUG 0.75 (0.51, 0.89), ST 0.90 (0.79, 0.96), and the SPWT 0.91 (0.81, 0.97). Standardized response means varied from .79 to 1.98, being greatest for the ST and 6MWT over the studied time intervals.

Conclusions
The test-retest estimates of the 6MWT, ST, and the SPWT met the requisite standards for making decisions at the individual patient level. All measures were responsive to detecting deterioration and improvement in the early postoperative period.
Influence of Sex on Toxicity and Treatment Outcome in Small-Cell Lung Cancer
Authors: Singh Simron , Parulekar Wendy , Murray Nevin , Feld Ronald , Evans William K. , Tu Dongsheng , Shepherd Frances A. 
Published: January 2005

Purpose Female sex has been shown consistently to be a favorable prognostic factor in small-cell lung cancer (SCLC). Studies have shown that women with other tumor types experience greater treatment toxicity, but there have been few studies of sex-related toxicity in SCLC. Patients and Methods This was a sex-based retrospective analysis of four SCLC trials conducted by the National Cancer Institute of Canada Clinical Trials Group between 1987 and 1999. The 1,006 patients (648 males and 358 females) received similar chemotherapy consisting of cyclophosphamide-doxorubicin-vincristine and etoposide-cisplatin. Toxicities examined included myelosuppression, stomatitis, vomiting, and infection. Other end points included dose reductions and omissions, response, and survival. Results Women experienced significantly more hematologic toxicity than men (grade 3 and 4 anemia, 16.3% v 7.6%, respectively, P < .001; grade 3 and 4 leukopenia, 80.4% v 69.2%, respectively, P = .0001). However, toxic death rates were similar for men and women (1.5% v 1.1%, respectively, P = .58). Women also had significantly more stomatitis and vomiting of all grades. Despite increased toxicity, 76% of females versus 73.4% of males received all six treatment cycles (P = .38), but 52% of females versus 43.4% of males had treatment delayed for 2 weeks or more (P = .022). Only 31.8% of females and 28.2% of males had at least one cycle of chemotherapy dose reduction (P = .23). The overall response rate was 80.3% for females and 66.9% for males (P < .0001), and the median survival time was 1.31 years for females compared with only 0.91 year for males (P < .0001). Conclusion Women experience more chemotherapy-related toxicity in the treatment of SCLC, but they also have increased response rates and survival.
Randomized Phase III Trial of Capecitabine Compared With Bevacizumab Plus Capecitabine in Patients With Previously Treated Metastatic Breast Cancer
Authors: Miller Kathy D. , Chap Linnea I. , Holmes Frankie A. , Cobleigh Melody A. , Marcom P. Kelly , Fehrenbacher Louis , Dickler Maura , Overmoyer Beth A. , Reimann James D. , Sing Amy P. , Langmuir Virginia , Rugo Hope S. 
Published: January 2005

Purpose This randomized phase III trial compared the efficacy and safety of capecitabine with or without bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. Patients and Methods Patients were randomly assigned to receive capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks, alone or in combination with bevacizumab (15 mg/kg) on day 1. The primary end point was progression-free survival (PFS), as determined by an independent review facility. Results From November 2000 to March 2002, 462 patients were enrolled. Treatment arms were balanced. No significant differences were found in the incidence of diarrhea, hand-foot syndrome, thromboembolic events, or serious bleeding episodes between treatment groups. Of other grade 3 or 4 adverse events, only hypertension requiring treatment (17.9% v 0.5%) was more frequent in patients receiving bevacizumab. Combination therapy significantly increased the response rates (19.8% v 9.1%; P = .001); however, this did not result in a longer PFS (4.86 v 4.17 months; hazard ratio = 0.98). Overall survival (15.1 v 14.5 months) and time to deterioration in quality of life as measured by the Functional Assessment Of Cancer Treatment—Breast were comparable in both treatment groups. Conclusion Bevacizumab was well tolerated in this heavily pretreated patient population. Although the addition of bevacizumab to capecitabine produced a significant increase in response rates, this did not translate into improved PFS or overall survival.
Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones
Authors: Norton Will H. , Mangoli Maryam , Lele Zsolt , Pogoda Hans-Martin , Diamond Brianne , Mercurio Sara , Russell Claire , Teraoka Hiroki , Stickney Heather L. , Rauch Gerd-Jörg , Heisenberg Carl-Philipp , Houart Corinne , Schilling Thomas F. , Frohnhoefer Hans-Georg , Rastegar Sepand , Neumann Carl J. , Gardiner R. Mark , Strähle Uwe , Geisler Robert , Rees Michelle , Talbot William S. , Wilson Stephen W. 
Published: January 2005

In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol-/- embryos,we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol-/- mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves.Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphénucleus and the trochlear motor nucleus are absent in mol-/- embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins.