bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignant insulinoma
Authors: Hirshberg Boaz , Cochran Craig , Skarulis Monica C. , Libutti Steven K. , Alexander H. Richard , Wood Bradford J. , Chang Richard , Kleiner David E. , Gorden Phillip 
Published: June 2005

AbstractBACKGROUNDMalignant insulinoma occurs in a few patients with insulinoma. Due to the small sample of patients, there are little data regarding their clinical manifestation as well as the preferred treatment modalities. The aims of the current study were to summarize the National Institutes of Health experience during the last two decades and to conduct a critical review of the current literature.METHODSThe authors identified 10 patients with metastatic insulinoma.RESULTSThe patients presented with four patterns of clinical behavior. First, four patients presented with lymph node metastasis and, after surgical excision, maintained a prolonged tumor‐free survival. Second, four patients presented with metastatic disease to the liver, which appeared years after the initial diagnosis and presumed curative surgery. Third, one patient presented with a large α‐fetoprotein‐secreting liver mass. Finally, 9 of the 10 patients had a prolonged survival. Various treatment modalities were used to control hypoglycemia. Short‐term benefits were most often achieved with embolization and diazoxide. Less successful modalities included radiofrequency ablation, radical debulking surgery, verapamil therapy, octreotide therapy, and chemotherapy.CONCLUSIONSThe current study, as well as others, suggested that metastatic insulinoma may have a variable natural history. After the initial surgical resection, the biology of the tumor, rather than any treatment modality, was most likely the major determinant of long‐term survival. Cancer 2005. © Published 2005 American Cancer Society.
The natural history of breast carcinoma in patients with ≥ 10 metastatic axillary lymph nodes before and after the advent of adjuvant therapy
Authors: Montero Alberto J. , Rouzier Roman , Lluch Ana , Theriault Richard L. , Buzdar Aman U. , Delaloge Suzette , Bermejo Begoñia , Le Monique , Kau Shu‐Wan , Dunant Ariane , Arriagada Rodrigo , Spielmann Marc , Garcia‐Conde Javier , Sahin Aysegul A. , Singletary Sonja E. , Hortobagyi Gabriel N. , Valero Vicente 
Published: June 2005

AbstractBACKGROUNDThe majority of patients with breast carcinoma with ≥ 10 metastatic axillary lymph nodes (ALNs) develop recurrent disease within 5 years from diagnosis. The purpose of the current study, performed retrospectively, was to characterize the natural history of this subset of patients, both before and after the advent of adjuvant anthracycline‐based chemotherapy and tamoxifen.METHODSRetrospectively, patients with primary breast carcinoma (N= 882) with ≥ 10 metastatic ALNs, treated between 1954 and 1998, were selected from 3 institutions: The University of Texas M. D. Anderson Cancer Center (Houston, TX); the Institut Gustave Roussy (Villejuif, France); and Hospital Clinico Universitario (Valencia, Spain). All patient data had been registered prospectively in clinical databases. One group consisted of 314 patients treated with locoregional therapy alone (no adjuvant therapy) from 1954 to 1983. The second group included 568 patients who received adjuvant anthracycline‐based chemotherapy between 1974 and 1998 with or without adjuvant tamoxifen.RESULTSThe median follow‐up time was 140 months. Disease‐free survival rates at 15 and 20 years for the no adjuvant therapy and adjuvant therapy groups were 17% and 16% versus 26% and 24%, respectively. The overall survival rates at 20 years for the no adjuvant therapy and the adjuvant therapy groups were 9% and 21%, respectively. By multivariate analysis, the independent factors associated with survival in the adjuvant therapy group were tumor size and the number of metastatic lymph nodes.CONCLUSIONSThe retrospective analysis suggested that adjuvant anthracycline‐based chemotherapy and hormonal therapy have altered the natural history in this high‐risk group of patients. However, despite such improvements, survival rates remained low, and innovative therapeutic approaches are, therefore, needed to improve clinical outcomes. Cancer 2005. © 2005 American Cancer Society.
The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it
Authors: Hay Elizabeth D. 
Published: June 2005

AbstractThis review centers on the role of the mesenchymal cell in development. The creation of this cell is a remarkable process, one where a tightly knit, impervious epithelium suddenly extends filopodia from its basal surface and gives rise to migrating cells. The ensuing process of epithelial–mesenchymal transformation (EMT) creates the mechanism that makes it possible for the mesenchymal cell to become mobile, so as to leave the epithelium and move through the extracellular matrix. EMT is now recognized as a very important mechanism for the remodeling of embryonic tissues, with the power to turn an epithelial somite into sclerotome mesenchyme, and the neural crest into mesenchyme that migrates to many targets. Thus, the time has come for serious study of the underlying mechanisms and the signaling pathways that are used to form the mesenchymal cell in the embryo. In this review, I discuss EMT centers in the embryo that are ready for such serious study and review our current understanding of the mechanisms used for EMT in vitro, as well as those that have been implicated in EMT in vivo. The purpose of this review is not to describe every study published in this rapidly expanding field but rather to stimulate the interest of the reader in the study of the role of the mesenchymal cell in the embryo, where it plays profound roles in development. In the adult, mesenchymal cells may give rise to metastatic tumor cells and other pathological conditions that we will touch on at the end of the review. Developmental Dynamics 233:706–720, 2005. © 2005 Wiley‐Liss, Inc.
Fly Six‐type homeodomain proteins Sine oculis and Optix partner with different cofactors during eye development
Authors: Kenyon Kristy L. , Li Dan Jun , Clouser Christopher , Tran Susan , Pignoni Francesca 
Published: June 2005

AbstractTwo members from the Six class of homeobox transcription factors, Sine oculis (SO) and Optix, function during development of the fly visual system. Differences in gain‐of‐function phenotypes and gene expression suggest that these related factors play distinct roles in the formation of the fly eye. However, the molecular nature of their functional differences remains unclear. In this study, we report the identification of two novel factors that participate in specific partnerships with Sine oculis and Optix during photoreceptor neurons formation and in eye progenitor cells. This work shows that different cofactors likely mediate unique functions of Sine oculis and Optix during the development of the fly eye and that the repeated requirement for SO function at multiple stages of eye development reflects the activity of different SO–cofactor complexes. Developmental Dynamics 234:497–504, 2005. © 2005 Wiley‐Liss, Inc.
Microarray analysis of zebrafish cloche mutant using amplified cDNA and identification of potential downstream target genes
Authors: Qian Feng , Zhen Fenghua , Ong Chinthing , Jin Suk‐Won , Meng Soo Hui , Stainier Didier Y.R. , Lin Shuo , Peng Jinrong , Wen Zilong 
Published: June 2005

AbstractZebrafish is an excellent model organism for studying vertebrate development and human disease. With the availability of increased numbers of zebrafish mutants and microarray chips, gene expression profiling has become a powerful tool for identification of downstream target genes perturbed by a specific mutation. One of the obstacles often encountered, however, is to isolate large numbers of zebrafish mutant embryos that are indistinguishable in morphology from the wild‐type siblings for microarray analysis. Here, we report a method using amplified cDNA derived from five embryos for gene expression profiling of the 18‐somite zebrafish cloche (clo) mutant, in which development of hematopoietic and endothelial lineages is severely impaired. In total, 31 differentially expressed target genes are identified, of which 13 have not been reported previously. We further determine that of these 13 new targets, 8 genes, including coproporphyrinogen oxidase (cpo), carbonic anhydrase (cahz), claudin g (cldn g), zinc‐finger–like gene 2 (znfl2), neutrophil cytosol factor 1 (ncf1), matrix metalloproteinase 13 (mmp13), dual specificity phosphatase 5 (dusp5), and a novel gene referred as zebrafish vessel‐specific gene 1 (zvsg1) are predominantly expressed in hematopoietic and endothelial cells. Comparative analysis demonstrates that this method is comparable and complementary to that of the conventional approach using unamplified sample. Our study provides valuable information for studying hematopoiesis and vessel formation. The method described here offers a powerful tool for gene expression profiling of zebrafish mutants in general. Developmental Dynamics 233:1163–1172, 2005. © 2005 Wiley‐Liss, Inc.
Neonatal dexamethasone induces premature microvascular maturation of the alveolar capillary network
Authors: Roth‐Kleiner Matthias , Berger Thomas M. , Tarek Mojmir R. , Burri Peter H. , Schittny Johannes C. 
Published: June 2005

AbstractPostnatal glucocorticoid treatment of preterm infants was mimicked by treating newborn rats with dexamethasone (0.1–0.01 μg/g, days 1–4). This regimen has been shown to cause delayed alveolarization. Knowing that microvascular maturation (transformation of double‐ to single‐layered capillary networks in alveolar septa) and septal thinning prevent further alveolarization, we measured septal maturation on electron photomicrographs in treated and control animals. In treated rats and before day 10, we observed a premature nonreversing microvascular maturation and a transient septal thinning, which both appeared focally. In vascular casts of both groups, we observed contacts between the two capillary layers of immature alveolar septa, which were predictive for capillary fusions. Studying serial electron microscopic sections of human lungs, we were able to confirm the postulated fusion process for the first time. We conclude that alveolar microvascular maturation indeed occurs by capillary fusion and that the dexamethasone‐induced impairment of alveolarization is associated with focal premature capillary fusion. Developmental Dynamics 233:1261–1271, 2005. © 2005 Wiley‐Liss, Inc.
Chk2/Cds1 protein kinase blocks apoptosis during early development of Xenopus laevis
Authors: Wroble Brian N. , Sible Jill C. 
Published: June 2005

AbstractEarly Xenopus laevis embryos possess cell cycles that do not arrest at checkpoints in response to damaged DNA. At the midblastula transition (MBT), embryos with damaged DNA undergo apoptosis. After the MBT, DNA damage triggers cell cycle arrest rather than apoptosis. The transition from checkpoint‐unregulated to checkpoint‐regulated cycles makes Xenopus embryos compelling for studying mechanisms regulating response to genomic damage. The DNA damage checkpoint is mediated by the Chk2/Cds1 kinase. Conflicting evidence implicates Chk2 as an inhibitor or promoter of apoptosis. To better understand the developmental function of Chk2, we expressed wild‐type (wt) and dominant‐negative (DN) Chk2 in Xenopus embryos. Wt‐Chk2 created a pre‐MBT checkpoint due to degradation of Cdc25A and phosphorylation of cyclin‐dependent kinases. Embryos expressing DN‐Chk2 developed normally until gastrulation and then underwent apoptosis. Conversely, low doses of wt‐Chk2 blocked radiation‐induced apoptosis. Therefore, Chk2 operates at a switch between cell cycle arrest or apoptosis in response to genomic assaults. Developmental Dynamics 233:1359–1365, 2005. © 2005 Wiley‐Liss, Inc.
Identification of a gene required for de novo DNA methylation of the zebrafish no tail gene
Authors: Shimoda Nobuyoshi , Yamakoshi Kimi , Miyake Akimitsu , Takeda Hiroyuki 
Published: June 2005

AbstractThe zebrafish no tail gene (ntl) is indispensable for tail and notochord development. We have shown previously that ntl is de novo methylated during early embryogenesis. To find the gene that de novo methylates ntl and understand the meaning of this methylation, we cloned seven genes that encode the conserved catalytic domain of methyltransferases. We found that injection of antisense morpholino oligonucleotides against one of them, termed dnmt7, into eggs significantly reduced the level of ntl methylation, although no apparent phenotype was induced by the injection. Inhibition of Dnmt7 activity did not change the level of genome‐wide methylation nor did it affect de novo methylation of injected plasmid DNA, indicating that Dnmt7 specifically methylates ntl in the genome. Developmental Dynamics 233:1509–1516, 2005. © 2005 Wiley‐Liss, Inc.
Osteopontin and related SIBLING glycoprotein genes are expressed by Sertoli cells during mouse testis development
Authors: Wilson Megan J. , Liaw Lucy , Koopman Peter 
Published: June 2005

AbstractMatrix proteins play important roles in tissue morphogenesis. We have studied the expression of genes encoding the related SIBLING glycoproteins osteopontin (OPN), bone sialoprotein (BSP), and dentin matrix protein (DMP) during the development of male and female gonads during mouse embryogenesis. Opn mRNA was expressed specifically by Sertoli cells of the developing testis cords, in the mesonephric tubules of both sexes, and, transiently, in the Müllerian ducts of both sexes, as determined by whole‐mount and section in situ hybridization. OPN protein was detected in the cytoplasm of Sertoli cells and luminal cells of the mesonephric tubules, with small amounts associated with the plasma membrane of germ cells. We found no defects in developing testes of Opn−/− mice using a range of cell type‐specific markers, suggesting that other SIBLING proteins may function in testis development. Dmp and Bsp mRNA was also expressed in the developing testis cords, supporting the view that all three SIBLING proteins may contribute to testis differentiation. Developmental Dynamics 233:1488–1495, 2005. © 2005 Wiley‐Liss, Inc.
Trialkoxysilyl‐Functionalized Silver(I) Carboxylates: New Building Blocks for the Synthesis of Immobilizable and Immobilized Homogeneous Catalysts
Authors: Vehlow Kati , Köhler Katrin , Blechert Siegfried , Dechert Sebastian , Meyer Franc 
Published: June 2005

AbstractPartly fluorinated trialkoxysilyl‐substituted carboxylic acids (RO)3Si(CH2)3N(R')C(O)(CF2)3COOH (3a: R = Et, R' = H; 3b: R = R' = Me) have been prepared in a straightforward synthesis from the respective trialkoxysilyl‐substituted primary and secondary amines and hexafluoroglutaric anhydride. Treatment with silver(I) oxide yields the corresponding silver carboxylates 4a,b which have been thoroughly characterized in solution and in the solid state, including an X‐ray crystallographic analysis of 4a. The molecular structure of 4a consists of archetypal carboxylate‐bridged disilver(I) pairs with a strong closed‐shell Ag–Ag (d10–d10) interaction and a unique intramolecular bond between a silyl ether group and the metal ion. In addition the amide oxygen atoms are involved in H‐bonding and in intermolecular silver coordination, giving rise to an unusual two‐dimensional network structure. Silyl‐free acid iPr2NC(O)(CF2)3COOH (5) and its silver salt 6 have been prepared and structurally characterized for comparison. It is shown that the trialkoxysilyl tail in 4a,b allows for convenient attachment of these silver complexes to silica surfaces, as is corroborated by DRIFT measurements. The immobilized silver carboxylates 7a,b exhibit remarkable stability and are expected to open an easy access to a wide variety of SiO2‐grafted transition metal catalysts via transfer of the carboxylate ligand in simple exchange reactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Tautomeric Self‐Dimerization and Molecular Recognition Properties of2‐Aminopyrimidinone Derivatives as Triple Hydrogen‐Bonding Modules in Molecular Assemblies
Authors: Abe Hajime , Takase Masayoshi , Doi Yasuhiro , Matsumoto Shinya , Furusyo Masaru , Inouye Masahiko 
Published: June 2005

AbstractA triple hydrogen‐bonding module based on 6‐alkynyl‐2‐amino‐3H‐pyrimidin‐4‐one was developed such as for self‐dimerization and for nucleobase recognition processes. The strength of the module for the self‐dimerization was determined by NMR and fluorimetric analyses in chloroform (ΔG298 = –22 to –23 kJ/mol). DFT calculations and X‐ray structure analysis showed that the self‐dimerization consists of the three‐point hydrogen‐bonding including two kinds of tautomers of the module in an ADD·DAA mode. Selective recognition of the module for a cytidine derivative was also observed, and the free energy change for the complexation (ΔG298 = –31 kJ/mol) is one of the highest values among triple hydrogen‐bonded complexes so far reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Synthesis and Comparative Glycosidase Inhibitory Properties of Reducing Castanospermine Analogues
Authors: Díaz Pérez Paula , García‐Moreno M. Isabel , Ortiz Mellet Carmen , García Fernández José M. 
Published: June 2005

AbstractThe feasibility of the intramolecular nucleophilic addition of the nitrogen atom in cyclic (thio)carbamates with a pseudo‐C‐nucleoside structure to the masked carbonyl group in aldose precursors in the synthesis of reducing (i.e., 5‐hydroxy)6‐oxaindolizidine frameworks is illustrated by the preparation of the 6‐epi, 7‐epi, 8‐epi and 6,8a‐di‐epi diastereomers of the potent glycosidase inhibitor (+)‐castanospermine. In all cases, the increased anomeric effect caused by the high sp2 character of the pseudoamide‐type nitrogen atom resulted in the pseudoanomeric hydroxy group being anchored in an axial orientation in aqueous solution, as in the aglycons in α‐glycosides. These analogs of the natural alkaloid showed a higher selectivity in the inhibition of α‐glucosidases. Structure/glycosidase inhibitory activity studies indicated that inversion of any hydroxy group resulted in a dramatic decrease in the inhibition potency, confirming the critical importance of a correct hydroxylation profile. In the case of (+)‐8‐epi‐6‐oxacastanospermine derivatives, with a hydroxylation profile with a structural complementarity to that of D‐galactose, a moderate but very selective inhibition of α‐galactosidase was observed, supporting the importance of a defined configuration at pseudoanomeric centres for anomeric specificity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Highly Methylated Purines and Purinium Salts as Analogues of Heteromines
Authors: Hocek Michal , Pohl Radek , Císařová Ivana 
Published: June 2005

AbstractThree new unsubstituted or N‐methylated derivatives of 2‐amino‐6,7,9‐trimethylpurinium iodides were prepared by quaternization of the corresponding 2‐amino‐6,7‐dimethylpurines. These intermediates were synthesized either by Pd‐catalysed cross‐coupling of 2‐amino‐6‐chloro‐9‐methylpurine with trimethylaluminium or by regioselective Fe‐catalysed cross‐coupling of 2,6‐dichloro‐9‐methylpurine with methylmagnesium chloride, followed by amination. Both the title purinium salts and the purine intermediates were studied by 15N NMR, and one example of the purinium salts also by X‐ray diffraction. None of the compounds exerted significant cytostatic activity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Detection and separation of nucleoside‐5'‐monophosphates of DNA by conjugation with the fluorescent dye BODIPY and capillary electrophoresis with laser‐induced fluorescence detection
Authors: Cornelius Michael , Wörth Christian G. C. T. , Kliem Hans‐Christian , Wiessler Manfred , Schmeiser Heinz H. 
Published: June 2005

AbstractWe investigated the separation and detection of the 5'‐monophosphates of 2'‐deoxynucleosides selectively conjugated with 4,4‐difluoro‐5,7‐dimethyl‐4‐bora‐3a,4a‐diaza‐s‐indacene‐3‐propionyl ethylene diamine hydrochloride (BODIPY FL EDA) at the 5'‐phosphate group using capillary electrophoresis with laser‐induced fluorescence detection (CE‐LIF). BODIPY conjugates of the four common deoxynucleoside‐5'‐monophosphates (2'‐deoxyguanosine‐5'‐monophosphate, 2'‐deoxyadenosine‐5'‐monophosphate, 2'‐deoxycytidine‐5'‐monophosphate, and thymidine‐5'‐monophosphate) were prepared and subjected to CE‐LIF to serve as standard compounds for peak assignment and to develop separation conditions for the analysis of DNA. BODIPY conjugates were detected and resolved by CE‐LIF after digestion of DNA or an oligonucleotide to 5'‐monophosphates by nuclease P1 (NP 1) and fluorescence labeling without further purification step. Comparative analyses of calf‐thymus DNA digested either with micrococcal nuclease/spleen phosphodiesterase to 3'‐monophosphates or with NP 1 to 5'‐monophosphates showed that both versions of the fluorescence postlabeling assay were equally efficient and sensitive. Moreover, using the same assay, 2'‐deoxyuridine and 2'‐deoxy‐5methylcytidine were identified in bisulfite treated DNA after NP 1 digestion indicating that fluorescence postlabeling of 2'‐deoxyribonucleoside‐5'‐monophosphates with BODIPY FL EDA and detection by CE‐LIF has the potential to determine DNA damage and genomic DNA methylation.
The impact of epistemic uncertainty on an earthquake loss model
Authors: Crowley Helen , Bommer Julian J. , Pinho Rui , Bird Juliet 
Published: June 2005

AbstractModels capable of estimating losses in future earthquakes are of fundamental importance for emergency planners, for the insurance and reinsurance industries, and for code drafters. Constructing a loss model for a city, region or country involves compiling databases of earthquake activity, ground conditions, attenuation equations, building stock and infrastructure exposure, and vulnerability characteristics of the exposed inventory, all of which have large associated uncertainties. Many of these uncertainties can be classified as epistemic, implying—at least in theory—that they can be reduced by acquiring additional data or improved understanding of the physical processes. The effort and cost involved in refining the definition of each component of a loss model can be very large, for which reason it is useful to identify the relative impact on the calculated losses due to variations in these components. A mechanically sound displacement‐based approach to loss estimation is applied to a test case of buildings along the northern side of the Sea of Marmara in Turkey. Systematic variations of the parameters defining the demand (ground motion) and the capacity (vulnerability) are used to identify the relative impacts on the resulting losses, from which it is found that the influence of the epistemic uncertainty in the capacity is larger than that of the demand for a single earthquake scenario. Thus, the importance of earthquake loss models which allow the capacity parameters to be customized to the study area under consideration is highlighted. Copyright © 2005 John Wiley & Sons, Ltd.