bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergy between imatinib and mycophenolic acid in inducing apoptosis in cell lines expressing Bcr-Abl
Authors: Gu Jing Jin , Santiago Lalaine , Mitchell Beverly S. 
Published: December 2004

AbstractBcr-Abl tyrosine kinase activity initiates a number of intracellular signaling cascades that result in leukemogenesis. Imatinib mesylate, a specific Bcr-Abl tyrosine kinase inhibitor, has been highly successful in the treatment of chronic myelogenous leukemia (CML). However, the emergence of imatinib resistance and the incomplete molecular response of a significant number of patients receiving this therapy have led to a search for combinations of drugs that will enhance the efficacy of imatinib. We have demonstrated that mycophenolic acid (MPA), a specific inosine monophosphate dehydrogenase (IMPDH) inhibitor that results in depletion of intracellular guanine nucleotides, is synergistic with imatinib in inducing apoptosis in Bcr-Abl-expressing cell lines. Studies of signaling pathways downstream of Bcr-Abl demonstrated that the addition of MPA to imatinib reduced the phosphorylation of both Stat5 and Lyn, a Src kinase family member. The phosphorylation of S6 ribosomal protein was also greatly reduced. These results demonstrate that inhibitors of guanine nucleotide biosynthesis may synergize with imatinib in reducing the levels of minimal residual disease in CML and lay the foundation for clinical trials in which IMPDH inhibitors are added to imatinib in patients who have suboptimal molecular responses to single agent therapy or who have progressive disease. (Blood. 2005; 105:3270-3277)
Functional analysis of pyrimidine 5′-nucleotidase mutants causing nonspherocytic hemolytic anemia
Authors: Chiarelli Laurent R. , Bianchi Paola , Fermo Elisa , Galizzi Alessandro , Iadarola Paolo , Mattevi Andrea , Zanella Alberto , Valentini Giovanna 
Published: December 2004

AbstractInherited pyrimidine 5′-nucleotidase type I (P5′N-1) deficiency is the third most common erythrocyte enzymopathy that causes hemolysis. Fourteen different mutations have been identified to date. We have investigated the molecular bases of the disease by studying the biochemical properties of the recombinant wild-type human enzyme and 4 variant proteins (D87V, L131P, N179S, and G230R) bearing missense mutations found in patients affected by nonspherocytic hemolytic anemia. P5′N-1 is a relatively stable protein and has essentially identical catalytic efficiency toward cytidine monophosphate (CMP) and uridine monophosphate (UMP). All investigated mutant proteins display impaired catalytic properties and/or reduced thermostability, providing a rationale for the pathological effects of the mutations. Despite the substantial changes in the kinetic and thermostability parameters, the enzyme activity detected in the red blood cells of patients homozygous for mutations L131P and G230R exhibits moderate alterations. This suggests that P5′N-1 deficiency is compensated, possibly by other nucleotidases or alternative pathways in nucleotide metabolism. Therefore, nucleotidase activity may not be considered a prognostic indicator in patients affected by the enzymopathy. (Blood. 2005;105:3340-3345)
Age differences in interrogative suggestibility: a comparison between young and older adults
Authors: Polczyk Romuald , Wesołowska Bogumiła , Gabarczyk Agnieszka , Minakowska Iwona , Supska Magdalena , Bomba Ewa 
Published: December 2004

AbstractSixty‐six young adults (M age: 22.3, SD=3.3, range 18–35), and 43 older adults (M age: 64.1, SD=9.5, range 49–88) were compared on interrogative suggestibility, as measured by the Gudjonsson Suggestibility Scale. Participants listened to a story and were then asked suggestive questions. Afterwards, they were told that they had made a number of errors, and they were questioned once again. The number of accepted suggestions gives an index called Yield 1, and the number of answers changed after negative feedback gives an index called Shift. Older adults scored higher on Yield, but not on Shift. The participants also completed measures of memory performance (Wechsler Memory Scale), and a self‐assessment of memory (Memory Assessment Clinics Self‐Rating Scale). Regression analyses showed that memory performance and memory self‐assessment were independent predictors of yielding to suggestive questions in the group of older adults, when controlling for the effects of age. No reliable independent predictor was identified in any of the groups for Shift. Copyright © 2004 John Wiley & Sons, Ltd.
Age, neuropsychological, and social cognitive measures as predictors of individual differences in susceptibility to the misinformation effect
Authors: Lee Kerry 
Published: December 2004

AbstractThis study examined the relationship between age, neuropsychological performance (indexed by the Wisconsin Card Sorting Test, California Verbal Learning Test, the backward digit span and the verbal paired associates scale, VPA), social cognitive status (indexed by the Children's Social Desirability and the Gudjonsson Suggestibility Scale), and susceptibility to the misinformation effect (Loftus, Miller, & Burns, 1978) in 65 children and adolescents. The predictors accounted for 17% to 22% of variation in the misinformation effect. In particular, participants with better VPA scores were more susceptible to the effect. In a secondary analysis involving interrogative suggestibility, better VPA scores correlated with lower suggestibility. These findings show that better associative memory can be correlated with either higher or lower suggestibility depending on the way in which participants are misled. Copyright © 2004 John Wiley & Sons, Ltd.
Memory and suggestibility in older adults: live event participation and repeated interview
Authors: Mueller‐Johnson Katrin , Ceci Stephen J. 
Published: December 2004

AbstractOne hundred and thirteen young (mean age: 20.2 years) and older adults (mean age: 76.4 years) participated in an event that entailed various relaxation techniques, such as a body massage and aromatherapy. On two separate occasions several weeks following participation, half of each group was given misleading information about certain aspects of the event, including suggestions that they had been massaged on parts of their body which had not been touched. Results showed that older adults were disproportionately influenced by the presentation of erroneous suggestions. These findings add to the small but growing body of knowledge about the vulnerability of older eyewitnesses. Copyright © 2004 John Wiley & Sons, Ltd.
Trisomy 13 due to rea(13q;13q) is caused by i(13) and not rob(13;13)(q10;q10) in the majority of cases
Authors: Bugge Merete , deLozier‐Blanchet Celia , Bak Mads , Brandt Carsten A. , Hertz Jens Michael , Nielsen Jytte Bieber , Duprez Laurance , Petersen Michael B. 
Published: December 2004

AbstractWe have used 20 PCR‐based DNA polymorphisms to determine whether trisomy 13 due to de novo rea(13q;13q) in six cases is caused by translocation (13q;13q) or isochromosome (13q;13q); to determine the parental origin of the rearrangements and the mechanisms of formation. The six probands were three liveborn children with clinical features characteristic of Patau's syndrome and three fetuses diagnosed prenatally by amniocentesis or CVS. Five cases were isochromosomes with two identical q arms, one of maternal and four of paternal origin. Only one case was a Robertsonian translocation of maternal origin. © 2004 Wiley‐Liss, Inc.
Tests for Monotonic Trend from Case‐Control Data: Cochran‐Armitage‐Mantel Trend Test, Isotonic Regression and Single and Multiple Contrast Tests
Authors: Leuraud K. , Benichou J. 
Published: December 2004

AbstractTests for a monotonic trend between an ordered categorical exposure and disease status are routinely carried out from case‐control data using the Mantel‐extension trend test or the asymptotically equivalent Cochran‐Armitage test. In this study, we considered two alternative tests based on isotonic regression, namely an order‐restricted likelihood ratio test and an isotonic modification of the Mantel‐extension test extending the recent proposal by Mancuso, Ahn and Chen (2001) to case‐control data. Furthermore, we considered three tests based on contrasts, namely a single contrast (SC) test based on Schaafsma's coefficients, the Dosemeci and Benichou (DB) test, a multiple contrast (MC) test based on the Helmert, reverse‐Helmert and linear contrasts and we derived their case‐control versions. Using simulations, we compared the statistical properties of these five alternative tests to those of the Mantel‐extension test under various patterns including no relationship, as well as monotonic and non‐monotonic relationships between exposure and disease status. In the case of no relationship, all tests had close to nominal type I error except in situations combining a very unbalanced exposure distribution and small sample size, where the asymptotic versions of the three tests based on contrasts were highly anticonservative. The use of bootstrap instead of asymptotic versions corrected this anticonservatism. For monotonic patterns, all tests had close powers. For non monotonic patterns, the DB‐test showed the most favourable results as it was the least powerful test. The two tests based on isotonic regression were the most powerful tests and the Mantel‐extension test, the SC‐ and MC‐tests had in‐between powers. The six tests were applied to data from a case‐control study investigating the relationship between alcohol consumption and risk of laryngeal cancer in Turkey. In situations with no evidence of a monotonic relationship between exposure and disease status, the three tests based on contrasts did not conclude in favour of a significant trend whereas all the other tests did. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Impact of thymectomy on the peripheral T cell pool in rhesus macaques before and after infection with simian immunodeficiency virus
Authors: Arron Sarah Tuttleton , Ribeiro Ruy M. , Gettie Agegnehu , Bohm Rudolph , Blanchard James , Yu Jian , Perelson Alan S. , Ho David D. , Zhang Linqi 
Published: December 2004

AbstractThe goal of this study was to define, by surgical removal of the thymus in juvenile rhesus macaques, the role of the thymus in peripheral T cell homeostasis and to assess the significance of thymic output in SIV infection. By monitoring the changes in phenotypic T cell markers as well as in the numbers of TCR excisional circles – a recently described marker for recent thymic emigrants – following thymectomy, we present evidence that surgical thymectomy in juvenile macaques results in a faster decay of peripheral CD4+ cells, but does not cause a substantial shift in CD45RA+ and CD45RA– populations. We were able to measure a thymic output of 0.32% and 0.21% per day of CD4+ and CD8+ cells, respectively. No compensatory extra‐thymic source was detected in lymphoid tissues, although there was a small compensatory increase in T cell proliferation in the peripheral T cell pool. After SIV infection, thymectomized animals did not have higher viral loads, greater T cell decay, or faster disease progression. We therefore conclude that peripheral destructive processes, rather than a loss of thymic output, appear to be the main causes of T cell depletion in SIV infection.See accompanying Commentary: http://dx.doi.org/10.1002/eji.200425643
T cell receptor‐induced lipid raft recruitment of the IκB kinase complex is necessary and sufficient for NF‐κB activation occurring in the cytosol
Authors: Sebald Andrea , Mattioli Ivan , Schmitz M. Lienhard 
Published: December 2004

AbstractTCR‐induced NF‐κB activation is necessary for the innate immune response and involves induced lipid raft recruitment of the IκB kinase (IKK) complex. In this study, we systematically investigated lipid raft recruitment of members of the NF‐κB activation pathway in human T cells. All upstream components leading to IKK activation were found constitutively or inducibly in lipid rafts, while the NF‐κB/IκB complex and phosphorylated forms of IKKα/β, IκBα and p65 are exclusively found in the cytosolic fraction. Disruption of raft organization precluded NF‐κB activation induced by T cell costimulation, but IL‐1‐triggered NF‐κB activation remained unaffected. Targeting of the IKK complex to lipid rafts caused constitutive IKK activation and NF‐κB DNA binding, which was further triggered upon T cell costimulation. Various experimental approaches revealed that costimulation‐induced IKKα/β activation loop phosphorylation is independent from IKKβ‐mediated transautophosphorylation, but rather involves phosphorylation by the IKK‐interacting protein NIK and its upstream activator COT.
Contemporaneous fluctuations in T cell responses to persistent herpes virus infections
Authors: Crough Tania , Burrows Jacqueline M. , Fazou Chrysa , Walker Susan , Davenport Miles P. , Khanna Rajiv 
Published: December 2004

AbstractThe classical paradigm for T cell dynamics suggests that the resolution of a primary acute virus infection is followed by the generation of a long‐lived pool of memory T cells that is thought to be highly stable. Very limited alteration in this repertoire is expected until the immune system is re‐challenged by reactivation of latent viruses or by cross‐reactive pathogens. Contradicting this view, we show here that the T cell repertoire specific for two different latent herpes viruses in the peripheral blood displayed significant contemporaneous co‐fluctuations of virus‐specific CD8+ T cells. The coordinated responses to two different viruses suggest that the fluctuations within the T cell repertoire may be driven by sub‐clinical viral reactivation or a more generalized ‘bystander’ effect. The later contention was supported by the observation that, while absolute number of CD3+ T cells and their subsets and also the cell surface phenotype of antigen‐specific T cells remained relatively constant, a loss of CD62L expression in the total CD8+ T cell population was coincident with the expansion of tetramer‐positive virus‐specific T cells. This study demonstrates that the dynamic process of T cell expansion and contractions in persistent viral infections is not limited to the acute phase of infection, but also continues during the latent phase of infection.
Specificity, magnitude, and kinetics of MOG‐specific CD8+ T cell responses during experimental autoimmune encephalomyelitis
Authors: Ford Mandy L. , Evavold Brian D. 
Published: December 2004

AbstractExperimental autoimmune encephalomyelitis (EAE) has traditionally been thought to be almost exclusively mediated by CD4+ effector T cells. Here, we provide evidence for the existence of mouse CD8+ T cells that are specific for an epitope of the myelin oligodendrocyte glycoprotein (MOG). Using a panel of truncated MOG peptides, we have identified the minimal epitope recognized by these T cells as MOG 37–46. This peptide, while possessing relatively low affinity for H‐2Db, efficiently stimulates IFN‐γ production from MOG‐specific CD8+ T cell lines in vitro and induces EAE in vivo. To further characterize the magnitude and kinetics of expansion of the MOG‐specific CD8+ T cell population in vivo, we used MOG 37–50/H‐2Db MHC tetramers to visualize MOG‐specific CD8+ effectors in the peripheral lymphoid organs and central nervous system during the course of EAE induction and progression. Our results identify MOG‐specific CD8+ T cells in the central nervous system prior to and after the onset of disease, suggesting that CD8+ T cells are a possible target for therapeutic intervention during EAE.
Synthesis of Group 14 Metal Enamido, Alkenyl, Imido and Alkenyl‐Amido Complexes from a Monoanionic Pyridyl‐1‐azaallyl Ligand
Authors: Leung Wing‐Por , So Cheuk‐Wai , Wu Yuen‐Sze , Li Hung‐Wing , Mak Thomas C. W. 
Published: December 2004

AbstractThe reactivity of the lithium pyridyl‐1‐azaallyl complex [Li{N(SiMe3)C(Ph)C(R)(C5H4N‐2)}]2 [R = SiMe3 (1) or H (10)] with group 14 metal halides has been studied under various conditions. It undergoes a salt‐elimination reaction with MCl2 (M = Ge, Sn or Pb) to form [Ge{C(C5H4N‐2)C(Ph)N(SiMe3)2}{N(SiMe3)C(Ph)C(SiMe3)(C5H4N‐2)}] (2), [M{N(SiMe3)C(Ph)C(SiMe3)(C5H4N‐2)}2] [M = Sn (3), Pb (4)], and [M{N(SiMe3)C(Ph)C(SiMe3)(C5H4N‐2)}Cl] [M = Ge (5), Sn (6), Pb (7)], where the azaaalyl moiety acts as a monodentate ligand. However, the reaction of 1 with GeCl4 or HSiCl3 forms [Ge{C(C5H4N‐2)C(Ph)N(SiMe3)}Cl2]2 (8) or [{(C5H4N‐2)C(SiMe3)C(Ph)N}(μ‐SiHCl)]2 (9), respectively, by elimination of both the lithium salt and Me3SiCl; the reaction of 10 with GeCl4 gives [{(C5H4N‐2)C(H)C(Ph)N}(μ‐GeCl2)]2 (11) in a similar manner. X‐ray structural analysis of compounds 2−5, 7−9 and 11 showed that the pyridyl‐1‐azaallyl ligand bonds to the metal center in enamido, alkenyl, alkenylamido, and imido bonding modes. A mechanism for the formation of these compounds is proposed and discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Asymmetric Cyclopropanation of Optically Active (1‐Diethoxyphosphoryl)vinyl p‐Tolyl Sulfoxide with Sulfur Ylides: A Rationale for Diastereoselectivity
Authors: Midura Wanda H. , Krysiak Jerzy A. , Cypryk Marek , Mikołajczyk Marian , Wieczorek Michał W. , Filipczak Agnieszka D. 
Published: December 2004

AbstractThe title sulfoxide (S)‐(+)‐1a was found to react with sulfur ylides affording the corresponding cyclopropanes in high yields. With fully deuterated dimethyl(oxo)sulfonium methylide, (CD3)2S(O)CD2, the cyclopropanation reaction occurred in a highly diastereoselective manner producing the cyclopropane 4a‐d2 as a major diastereomer in which the newly formed quaternary α‐carbon atom is chiral due to isotopic substitution (CH2 vs. CD2). The diastereomer 4b‐d2, having the opposite configuration at the α‐carbon atom, was obtained starting form the 2,2‐dideuterio substituted vinyl sulfoxide, (S)‐(+)‐1a‐d2, and the nondeuterated ylide. The diastereomeric ratio in both reactions was found to be ca. 10:1. The reaction of (S)‐(+)‐1a with diphenylsulfonium isopropylide yielded the cyclopropane (+)‐7 as a single diastereomer. X‐ray structural studies of the crystalline 1‐phosphorylvinyl sulfoxide 9 as well as density functional calculations (B3LYP/6‐31G*) on (1‐phosphoryl)vinyl sulfoxides revealed the origin of the experimentally observed diastereoselectivities and allowed us to propose a transition state model for the cyclopropanation reaction of chiral 1‐phosphorylvinyl sulfoxides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Advanced numerical simulation of heat transfer problems
Authors: Ikegawa Masahiro , Kaiho Masayuki , Hayasaka Atsushi 
Published: December 2004

AbstractThis paper describes two kinds of practical numerical techniques for heat transfer problems. One is a parallel large eddy simulation technique with heat transfer using tetrahedral finite elements and the other is the Voxel method using a uniform grid combined with the discrete element method for liquid–solid two‐phase flow problems. These two approaches are taken to be the candidates for the practical use of large‐scale heat transfer analysis for various kinds of problems. The former can reduce the overall computing time in performing a large‐scale heat transfer analysis through the combined use of an automatic mesh generation software, and the latter is very useful and efficient to analyse a complicated heat transfer phenomena such as a liquid–solid two‐phase flow in a fluidized bed. Numerical examples for both approaches show fairly good agreement with experimental results and these two methods are demonstrated to be powerful tools for analysing large‐scale and complicated heat transfer problems. Copyright © 2004 John Wiley & Sons, Ltd.
β‐Catenin (CTNNB1) gene amplification: A new mechanism of protein overexpression in cancer
Authors: Suriano Gianpaolo , Vrcelj Nikoleta , Senz Janine , Ferreira Paulo , Masoudi Hamid , Cox Kelley , Nabais Sergio , Lopes Carlos , Machado José Carlos , Seruca Raquel , Carneiro Fatima , Huntsman David G. 
Published: December 2004

Abstractβ‐Catenin nuclear translocation is frequently observed in different types of malignancies, including gastric cancer. In gastric cancer, however, the molecular mechanisms leading to accumulation of this protein in the nucleus remain unknown. In this setting, β‐catenin (CTNNB1) mutations have been reported, but studies of mutation frequency have yielded conflicting results. Mutations or silencing of other partners of β‐catenin (i.e., APC and AXIN) are also considered rare genetic events in gastric tumorigenesis. Gene amplification is a common mechanism of activation and/or overexpression of oncogenes in gastric and other cancers. In this study, we investigated whether gene amplification is a possible mechanism of β‐catenin activation in gastric cancer by determining its presence in 49 patients with gastric cancer and two gastric‐derived cell lines (KATO III and ST2957). Using fluorescence in situ hybridization, we identified β‐catenin amplification in one of the tumor samples as well as in KATO III cells. β‐Catenin immunostaining revealed nuclear translocation of the protein in both cases. In the KATO III cells, β‐catenin overexpression was confirmed by quantitative real‐time PCR and Western blot analyses and β‐catenin gene amplification by Southern blot analysis and multiplex ligation probe amplification. In the KATO III cell line, no correlation was found between β‐catenin nuclear translocation and increased expression of the WNT1 target gene CCND1 (cyclin D1). Our data suggest that gene amplification is a possible mechanism of β‐catenin overexpression in cancer. © 2004 Wiley‐Liss, Inc.
Dietary flavonols and flavonol‐rich foods intake and the risk of breast cancer
Authors: Adebamowo Clement A. , Cho Eunyoung , Sampson Laura , Katan Martijn B. , Spiegelman Donna , Willett Walter C. , Holmes Michelle D. 
Published: December 2004

AbstractLaboratory and animal studies suggest that dietary flavonols may reduce breast cancer risk but there are limited epidemiological studies. We computed flavonol intakes from dietary data collected by validated food frequency questionnaires in 1991 and 1995 from 90,630 women in the Nurses Health Study II. Using multivariate relative risks (RR) and 95% confidence intervals (95% CI), we evaluated the association of flavonol intake with breast cancer risk in women who were premenopausal and aged between 26 and 46 years at baseline in 1991. During 8 years of follow‐up, we documented 710 cases of invasive breast cancer. The multivariate RR (95% CI), comparing highest to lowest quintiles of cumulative average intake, was 1.05 (0.83, 1.34; p‐value for test of trend = 0.96) for the sum of flavonols and there were no associations seen between individual flavonols such as kaempferol, quercetin and myricetin and breast cancer risk. The multivariate RR (95% CI), comparing highest to lowest quintiles of cumulative average intake, was 0.94 (0.72, 1.22; p‐value for test of trend = 0.54) for sum of flavonol‐rich foods. Among the major food sources of flavonols, we found a significant inverse association with intake of beans or lentils but not with tea, onions, apples, string beans, broccoli, green pepper and blueberries. The multivariate RR (95% CI), comparing the highest category (2 or more times a week) of cumulative average beans or lentils intake with the lowest category (less than once a month), was 0.76 (0.57, 1.00; p‐value for test of trend = 0.03). While we found no overall association between intake of flavonols and risk of breast cancer, there was an inverse association with intake of beans or lentils that merits further evaluation. © 2004 Wiley‐Liss, Inc.