bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of new translocations involving ETV6 in hematologic malignancies by fluorescence in situ hybridization and spectral karyotyping
Authors: Odero María D. , Carlson Katrin , Calasanz María J. , Lahortiga Idoya , Chinwalla Vandana , Rowley Janet D. 
Published: November 2004

AbstractTEL/ETV6 is the first transcription factor identified that is specifically required for hematopoiesis within the bone marrow. This gene has been found to have multiple fusion partners; 35 different chromosome bands have been involved in ETV6 translocations, of which 13 have been cloned. To identify additional ETV6 partner genes and to characterize the chromosomal abnormalities more fully, we studied bone marrow samples from patients known to have rearrangements of 12p, using fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY). FISH analysis was done with 14 probes located on 12p12.1 to 12p13.3. Nine ETV6 rearrangements were identified using FISH. The aberrations include t(1;12)(p36;p13), t(4;12)(q12;p13) (two patients), t(4;12)(q22;p13), t(6;12)(p21;p13), der(6)t(6;21)(q15;q?)t(12;21)(p13;q22), t(6;12)(q25;p13), inv(12)(p13q24), and t(2;2;5;12;17)(p25;q23;q31;p13;q12). Six new ETV6 partner bands were identified: 1p36, 4q22, 6p21, 6q25, 12q24, and 17q12. Our present data as well previous data from us and from other researchers suggest that ETV6 is involved in 41 translocations. The breakpoints in ETV6 were upstream from the exons coding for the HLH (helix‐loop‐helix) domain in six cases. Although cytogenetic analysis identified 12p abnormalities in all cases, FISH and SKY detected new and unexpected chromosomal rearrangements in many of them. Thus, complete characterization of the samples was achieved by using all three techniques in combination. © 2001 Wiley‐Liss, Inc.
Multivariate analyses of genomic imbalances in solid tumors reveal distinct and converging pathways of karyotypic evolution
Authors: Höglund Mattias , Gisselsson David , Mandahl Nils , Johansson Bertil , Mertens Fredrik , Mitelman Felix , Säll Torbjörn 
Published: November 2004

AbstractA total of 3,016 malignant solid tumors (kidney, colorectal, breast, head and neck, ovarian, and lung carcinomas, neuroglial tumors, malignant melanoma, and testicular germ cell tumors) were selected for statistical analyses regarding karyotypic evolution. Genomic imbalances, i.e., net gains and losses, present in more than 5% of each tumor type were identified. Individual tumors were then classified with respect to absence or presence of these imbalances. To analyze for possible patterns of correlated imbalances, principal component analyses (PCA) were performed. Furthermore, algorithms were developed to analyze the temporal order of the imbalances, as well as the possible selection for early or late appearance in the karyotypic evolution. By analyzing the temporal order of imbalances common to many tumor types, a general order for nine of these emerged, namely, +7, −3p, −6q, −1p, −8p, −17p, −9p, −18, and −22. The distributions of the number of imbalances per case revealed a geometrical distribution, ranging from one to nine imbalances per tumor, in the majority of the tumor types. In tumor types in which cases with a high number of imbalances per case were frequent, notably head and neck, ovarian, and lung carcinomas, the overall distributions were bimodal, indicating the presence of two modes of chromosome evolution. By combining data from the PCA with the temporal analyses, it was possible to identify karyotypic pathways. It was found that the majority of the tumor types displayed more than one cytogenetic route, but, as the karyotypic evolution continued, these converged to a common pathway. © 2001 Wiley‐Liss, Inc.
Spectral karyotyping reveals 17;22 fusions in a cytogenetically atypical dermatofibrosarcoma protuberans with a large marker chromosome as a sole abnormality
Authors: Mrózek Krzysztof , Iliszko Mariola , Ryś Janusz , Babińska Małgorzata , Niezabitowski Aleksander , Bloomfield Clara D. , Limon Janusz 
Published: November 2004

AbstractThe presence of an extra ring chromosome containing material from 17q and 22q, or, less frequently, a t(17;22)(q22;q13), is a cytogenetic hallmark of dermatofibrosarcoma protuberans (DFSP). However, occasionally tumors with other, atypical karyotypes are encountered. We describe a case of recurrent DFSP without a ring chromosome or a t(17;22) on standard cytogenetic analysis. In all cells analyzed by G‐banding, an additional, large marker chromosome was present as a sole abnormality. This chromosome apparently included chromosome 8 or the 8q arm, but the origin of its remaining part could not be determined with certainty. To characterize further the abnormal chromosome, we applied spectral karyotyping (SKY). SKY confirmed the presence of an extra chromosome 8 or arm 8q in the marker and showed that its remaining part was composed of segments from chromosomes 7, 17, 21, and 22, with two copies of a 17;22 fusion. Our results and the literature data suggest that, in addition to a specific 17;22 fusion, amplification of material from chromosomes 17, 22, 8, 5, 7, and 21 may play a role in DFSP development and/or progression. Furthermore, our case demonstrates the usefulness of SKY in detection of a diagnostically relevant 17;22 fusion in DFSP patients who have unusual karyotypic features. © 2001 Wiley‐Liss, Inc.
Coduplication of the MLL and FLT3 genes in patients with acute myeloid leukemia
Authors: Jamal Rahman , Taketani Takeshi , Taki Tomohiko , Bessho Fumio , Hongo Teruaki , Hamaguchi Hiroyuki , Horiike Shigeo , Taniwaki Masafumi , Hanada Ryoji , Nakamura Hideo , Hayashi Yasuhide 
Published: November 2004

AbstractTandem duplication (TD) of the MLL or FLT3 gene in acute myeloid leukemia (AML) has been reported. We examined whether TD of these two genes occurs simultaneously. We analyzed 13 AML and 2 myelodysplastic syndrome patients, including 6 adult patients with trisomy 11 and 9 pediatric patients with TD of the FLT3 gene, using RT‐PCR followed by sequencing. Among these, TD of the MLL and FLT3 genes was found in 5 and 10 patients, respectively. Notably, TD of both the MLL and FLT3 genes (coduplication) was detected in two AML patients, who died 6 and 14 months after diagnosis. TD of these two genes in AML is rare; thus, coduplication of these genes in the same patient is predicted to be very rare. Although the mechanisms of TD of both genes are different, development of TD of both genes may be related to an unknown similar etiology in leukemia because the frequency of coduplication of these genes in a single patient is considered to be very low. Further studies of the coduplication of these genes in AML patients may lead to the clarification of its mechanism and clinical implications. © 2001 Wiley‐Liss, Inc.
Lymphoid gene expression as a predictor of risk of secondary brain tumors
Authors: Edick Mathew J. , Cheng Cheng , Yang Wenjian , Cheok Meyling , Wilkinson Mark R. , Pei Deqing , Evans William E. , Kun Larry E. , Pui Ching‐Hon , Relling Mary V. 
Published: November 2004

AbstractGene expression profiles are tissue‐specific but may also reflect germ‐line‐driven expression patterns across tissue types. Previously, using a targeted pharmacologic approach, we identified germ‐line polymorphisms in a single gene (thiopurine methyltransferase) associated with the risk of irradiation‐ and chemotherapy‐induced secondary brain tumors in children with acute lymphoblastic leukemia (ALL). To identify additional candidate genetic risk factors, in identically treated patients, we compared the gene expression profiles of diagnostic ALL blasts of those who did develop irradiation‐associated brain tumors (n = 9) with the profiles from those who did not (n = 33). Weighted rank regression was used to identify 33 probe sets associated with the time‐dependent development of brain tumors; k‐means clustering (k = 2) identified 2 groups that differed significantly in cumulative incidence of brain tumors (P = 0.012). Permutation analysis was used to estimate the probability (P = 0.18) of obtaining 2 such clusters by chance. Linear discriminant analysis (time‐independent categorization of outcome) was used to identify 70 probe sets whose expression differentiated between the 2 groups of patients. Permutation analyses (n = 1,000) was used to estimate the probability of selecting these probe sets by chance (P = 0.055). Five probe sets were in common between the time‐independent and time‐dependent methods. The distinguishing genes are involved in neural growth (FGFR1) and in nuclear trafficking (HNRPL, KPNB1). These data suggest that gene expression profiling from accessible tissues may identify targets involved in therapy‐related malignancies in unrelated tissues. (
). © 2004 Wiley‐Liss, Inc.
Formation of der(19)t(1;19)(q23;p13) in acute lymphoblastic leukemia
Authors: Paulsson Kajsa , Horvat Andrea , Fioretos Thoas , Mitelman Felix , Johansson Bertil 
Published: November 2004

AbstractThe t(1;19)(q23;p13), which results in a fusion of TCF3 (previously E2A) at 19p13 with PBX1 at 1q23, is one of the most common translocations in acute lymphoblastic leukemia (ALL). It is seen either as a balanced t(1;19) or as an unbalanced der(19)t(1;19); occasional cases with coexisting t(1;19)‐ and der(19)‐positive clones also have been described. Although it generally has been assumed that the unbalanced form arises from the balanced t(1;19) through loss of the derivative chromosome 1 followed by duplication of the normal homologue, this has never been proved. At least two other mechanisms are possible for the formation of the der(19): an initial trisomy 1 followed by translocation and subsequent loss of the der(1) or a rearrangement during the G2 phase of the cell cycle, with the derivative chromosomes 1 and 19 ending up in separate daughter cells. The different alternatives may be distinguished by investigation of markers proximal to the breakpoint in 1q23 because they would be expected to lead to different allelic patterns. Thus, loss of heterozygosity as a result of the presence of uniparental disomy (UPD)—both copies of a chromosome being derived from only one parent—for chromosome 1 would be present in all der(19)‐harboring cases arising via the duplication pathway and in one‐third of cases arising via the trisomy pathway, but in none of the der(19) formed via the G2 pathway. In this study, we used quantitative fluorescence PCR with polymorphic microsatellite markers to investigate chromosomes 1 and 19 in two t(1;19)‐ and four der(19)‐positive ALLs. None of the der(19) cases displayed UPD for chromosome 1, excluding that this aberration arises through the duplication pathway. Because previous findings of cases with coexisting t(1;19) and der(19) clones are difficult to explain if the translocation originated in G2, the present results suggest that an unbalanced der(19) may arise from an initial trisomy 1 followed by t(1;19) translocation and loss of the derivative chromosome 1. © 2004 Wiley‐Liss, Inc.
Evaluating associations of haplotypes with traits
Authors: Schaid Daniel J. 
Published: November 2004

AbstractHaplotypes have played a major role in the study of highly‐penetrant single‐gene disorders, and recent evidence that the human genome has hot‐spots and cold‐spots for recombination have suggested that haplotype‐based methods may play a key role in the study of common complex traits. This report reviews the motivation of using haplotypes for the study of the genetic basis of human traits, ranging from biologic function, to statistical power advantages of haplotypes, to linkage disequilibrium fine‐mapping. Recent developments of regression models for haplotype analyses are reviewed, offering a synthesis of current methods, as well as their limitations and areas that require further research. Regression models provide significant advantages, such as the ability to control for non‐genetic covariates, the effects of the haplotypes can be modeled, step‐wise selection can be used to screen for a subset of markers that explain most of the association, haplotype × environment interactions can be evaluated, and regression diagnostics are well developed. Despite these strengths, the current regression methods tend to lack the sophisticated population genetic perspectives offered by coalescent and other similar approaches. Future work that links regression methods with population genetic models may prove beneficial.Genet. Epidemiol. © 2004 Wiley‐Liss, Inc.
SNPs, haplotypes, and model selection in a candidate gene region: The SIMPle analysis for multilocus data
Authors: Conti David V. , Gauderman W. James 
Published: November 2004

AbstractModern molecular techniques make discovery of numerous single nucleotide polymorphims (SNPs) in candidate gene regions feasible. Conventional analysis relies on either independent tests with each variant or the use of haplotypes in association analysis. The first technique ignores the dependencies between SNPs. The second, though it may increase power, often introduces uncertainty by estimating haplotypes from population data. Additionally, as the number of loci expands for a haplotype, ambiguity in interpretation increases for determining the underlying genetic components driving a detected association. Here, we present a genotype‐level analysis to jointly model the SNPs via a SNP interaction model with phase information (SIMPle) to capture the underlying haplotype structure. This analysis estimates both the risk associated with each variant and the importance of phase between pairwise combinations of SNPs. Thus, rather than selecting between genotype‐ or haplotype‐level approaches, the SIMPle method frames the analysis of multilocus data in a model selection paradigm, the aim to determine which SNPs, phase terms, and linear combinations best describe the relation between genetic variation and a trait of interest. To avoid unstable estimation due to sparse data and to incorporate both the dependencies among terms and the uncertainty in model selection, we propose a Bayes model averaging procedure. This highlights key SNPs and phase terms and yields a set of best representative models. Using simulations, we demonstrate the utility of the SIMPle model to identify crucial SNPs and underlying haplotype structures across a variety of causal models and genetic architectures. Genet. Epidemiol. © 2004 Wiley‐Liss, Inc.
Hippocampus and remote spatial memory in rats
Authors: Clark Robert E. , Broadbent Nicola J. , Squire Larry R. 
Published: November 2004

AbstractDamage to the hippocampus typically produces temporally graded retrograde amnesia, whereby memories acquired recently are impaired more than memories acquired remotely. This phenomenon has been demonstrated repeatedly in a variety of species and tasks. It has also figured prominently in theoretical treatments of memory and hippocampal function. Yet temporally graded retrograde amnesia has not been demonstrated following hippocampal damage in spatial tasks like the water maze. We have assessed recent and remote spatial memory following hippocampal lesions in three different tests of spatial memory: (1) the standard water maze; (2) the Oasis maze, a dry‐land version of the water maze; and (3) the annular water maze, where training and testing occur within a circular corridor. Training protocols were developed for each task such that retention of spatial memory could be expressed after very long retention intervals. In addition, retention in each task was assessed with single probe trials so that the assessment of remote memory did not depend on the ability to relearn across multiple trials. The findings were consistent across the three tasks. In the standard water maze (Experiment 1), spatial memory was impaired after training–surgery intervals of 1 day, 8 weeks, or 14 weeks. Similarly, in the Oasis maze (Experiment 2), spatial memory was impaired after training–surgery intervals of 1 day and 9 weeks. Finally, in the annular water maze (Experiment 3), spatial memory was impaired after training–surgery intervals of 9 weeks and 14 weeks. Dorsal hippocampal lesions impaired performance to the same extent as complete lesions. The impairment in remote spatial memory could reflect disruption of previously acquired spatial information. Alternatively, it is possible that in these tasks hippocampal lesions might produce an impairment in performance that prevents the expression of an otherwise intact spatial memory. Published 2004 Wiley‐Liss, Inc.
Expression and prognostic value of lactoferrin mRNA isoforms in human breast cancer
Authors: Benaïssa Monique , Peyrat Jean‐Philippe , Hornez Louis , Mariller Christophe , Mazurier Joël , Pierce Annick 
Published: November 2004

AbstractWe investigated the expression levels of human lactoferrin (Lf), a steroid hormone‐inducible gene product the expression of which is often altered during oncogenesis, and of Δ‐lactoferrin (ΔLf), its alternative isoform, which has been shown to be absent from tumor cell lines in commonly used human breast epithelial cell lines, using semiquantitative RT‐PCR. Both mRNAs were detected but with levels of expression lower than those found in normal breast epithelial cells. This downregulation was much more visible forΔLfsince its expression was either significantly diminished (BT‐20, MCF‐7 cell lines) or practically absent (MDA‐MB‐231, T‐47D, HBL 100 cell lines). In order to determine whetherLfgene products are useful prognosic tools, we further analyzed their expression levels in 99 primary breast cancer biopsies. ΔLf transcripts were found in all of the samples, whereas Lf transcripts were found in 88% of them. Lf and ΔLf expression levels were positively correlated (p= 0.003). Lf expression was related to tumor type with a higher recovery in lobular‐type tumors (p= 0.04). ΔLf expression was related to the histoprognostic grading (p= 0.02). In univariate analyses, ΔLf and Lf expressions were prognosis parameters, high concentrations being associated with a longer overall survival. © 2004 Wiley‐Liss, Inc.
Poly(N‐isopropylacrylamide) copolymer films as vehicles for the sustained delivery of proteins to vascular endothelial cells
Authors: Kavanagh C. A. , Gorelova T. A. , Selezneva I. I. , Rochev Y. A. , Dawson K. A. , Gallagher W. M. , Gorelov A. V. , Keenan A. K. 
Published: November 2004

AbstractThe aim of this study was to establish the capacity of thermoresponsive poly(N‐isopropylacrylamide) copolymer films to deliver bioactive concentrations of vascular endothelial growth factor (VEGF165) to human aortic endothelial cells (HAEC) over an extended time period. Films were prepared using a 50:50 (w/w) mixture of non‐crosslinkable and crosslinkable copolymers of the following monomer compositions (w/w): 85:15, N‐isopropylacrylamide (NiPAAm):N‐tert‐butylacrylamide (NtBAAm); and 85:13:2 NiPAAm:NtBAAm:acrylamidobenzophenone (ABzPh, crosslinking agent), respectively. After crosslinking by UV irradiation, the ability of films to incorporate a fluorescently labeled carrier protein (FITC‐labeled BSA, 1 mg loaded per film), at 4°C, was first established. Incorporation into the matrix was confirmed by the observation that increasing film thickness from 5 to 10 μm increased release from collapsed films at 37°C (1.76 ± 0.15 and 10.98 ± 3.38 μg/mL, respectively, at 24 h postloading) and that this difference was maintained at 5 days postloading (1.81 ± 0.25 and 13.8 ± 2.3 μg/mL, respectively). Incorporation was also confirmed by visualization using confocal microscopy. When 10‐μm films were loaded with a BSA solution (1 mg/mL) containing VEGF165 (3 μg/mL), sustained release of VEGF165 was observed (10.75 ± 3.11 ng at 24 h; a total of 31.32 ± 8.50 ng over 7 days). Furthermore, eluted VEGF165 increased HAEC proliferation by 18.2% over control. The absence of cytotoxic species in medium released from the copolymer films was confirmed by the lack of effect of medium (incubated with copolymer films for 3 days) on HAEC viability. In conclusion this study has shown that NiPAAm:NtBAAm copolymers can be loaded with a therapeutic protein and can deliver bioactive concentrations to human vascular endothelial cells over an extended time period. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 72A: 25–35, 2005
Elution from light‐cured dental composites: Comparison of trimethacrylate and dimethacrylate as base monomers
Authors: Kim Joong‐Gon , Chung Chan‐Moon 
Published: November 2004

AbstractThe effect of the number of functional units on a monomer on the elution property of dental composites was first studied. Elution from a composite of a trifunctional methacrylate, 1,1,1‐tris[4‐(2′‐hydroxy‐3′‐methacryloyloxypropoxy)phenyl]ethane (THMPE), was compared to that of bis‐GMA, a typical difunctional base monomer in current dental composites. The degrees of cure and the water solubilities of composites prepared from the two kinds of methacrylates were measured. The concentration of unreacted methacrylates (base monomer and diluent) present in the photo‐cured composites as well as the quantity of the methacrylates eluted into water (or 75%, volume fraction, of ethanol in water) from the composites were determined by high‐performance liquid chromatography (HPLC). THMPE‐based composites showed lesser amounts of residual and eluted methacrylates when compared with bis‐GMA composites. This is attributed to the higher degree of functionality and larger molecular size of THMPE compared with those of bis‐GMA. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 72B: 328–333, 2005
Static mechanical properties of hydroxyapatite (HA) powder‐filled acrylic bone cements: Effect of type of HA powder
Authors: Morejón Lizette , Mendizábal Alonso Eduardo , García‐Menocal José Angel Delgado , Ginebra María Pau , Aparicio Conrado , Mur Francisco Javier Gil , Marsal Montserrat , Davidenko Natalia , Ballesteros María E. , Planell Josep Anton 
Published: November 2004

AbstractThis work reports on the effect of the amount (0, 10, and 30 wt %) and type of HA powder incorporated into an acrylic bone cement on the tensile properties, compression properties, and fracture toughness. The three different types of HA powders used were synthesized in the laboratory and coated with a silane agent prior to incorporation into the cement powder, and differed in particle size, water content, surface area, and crystallinity. It was found that the inclusion of any type of HA powder led to an increase in the tensile modulus (ET), but all the other mechanical properties of the cement decreased (relative to the values of the unfilled cement). The increase in ET is attributed to the good adhesion between the filler and the cement matrix, which is due to the silane coating agent. The decrease in the other mechanical properties may be a consequence of HA powder agglomeration and porosity. Hydroxyapatite morphology and crack‐growth mechanisms were analyzed by scanning electronic microscopy (SEM). © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 72B: 345–352, 2005
Enzymatic synthesis of [1‐14C‐N‐acetyl, P18O2] cytidine monophosphate neuraminic acid
Authors: Burke Erin E. , Horenstein Nicole A. 
Published: November 2004

AbstractA method for the enzymatic synthesis of [1‐14C‐N‐acetyl, P18O2] cytidine monophosphate neuraminic acid (CMP‐NeuAc) is described. Central to the synthesis of [1‐14C‐N‐acetyl, P18O2]CMP‐NeuAc was the enzymatic preparation of [γ‐P18O3]ATP for use in a reaction with uridine kinase and cytidine to provide 5′‐[P18O3]CMP. The [1‐14C‐N‐acetyl, P18O2]CMP‐NeuAc isotopomer was then synthesized from a reaction involving nucleoside monophosphate kinase, pyruvate kinase and CMP‐NeuAc synthetase. The isolated reaction yield was 35%. Copyright © 2004 John Wiley & Sons, Ltd.