bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotypic and phenotypic progression in endometrial tumorigenesis: Determining when defects in DNA mismatch repair and KRAS2 occur
Authors: Cohn David E. , Mutch David G. , Herzog Thomas J. , Rader Janet S. , Dintzis Suzanne M. , Gersell Deborah J. , Todd Christina R. , Goodfellow Paul J. 
Published: August 2002

AbstractWe set out to determine the relative timing of loss of DNA mismatch repair and KRAS2 mutation in endometrial tumorigenesis. We studied endometrial carcinoma (CA) and synchronous atypical endometrial hyperplasia (AEH), the premalignant precursor of endometrial cancer. Carcinoma and hyperplasia were investigated for loss of mismatch repair as evidenced by microsatellite instability (MSI) and for KRAS2 mutations. Endometrial cancers previously shown to be MSI‐positive were evaluated for KRAS2 codon 12 and 13 mutations. DNA was isolated from foci of AEH concomitant with, but physically remote from, the cancers by use of tissues prepared by laser capture microdissection (LCM). The AEH DNAs were then assessed for MSI and KRAS2 mutations. Of 210 endometrial CAs investigated, 51 (26%) were MSI‐positive, and among those, 21 (41%) arose concomitantly with AEH. Of 41 foci of AEH (mean, two foci per patient) investigated, 34 (83%) were MSI‐positive. KRAS2 mutations were seen in 5/51 (10%) MSI‐positive carcinomas. From the five patients informative for both KRAS2 mutation and MSI, 10 foci of AEH were available for investigation. All 10 AEH specimens (100%) were MSI‐positive, and six (60%) had the KRAS2 mutation present in the coexisting CA. The observation that some MSI‐positive AEH specimens lack the KRAS2 mutation seen in the coexisting CA supports a model in which loss of DNA mismatch repair precedes KRAS2 mutation. However, in addition to the absence of KRAS2 mutations in AEH, we discovered mutations in LCM hyperplasia and carcinoma specimens that were not present in the portion of the cancers originally investigated. These discordant genotypes suggest genetic heterogeneity in endometrial hyperplasia and concomitant cancer. © 2001 Wiley‐Liss, Inc.
Wnt‐6 is expressed in the ureter bud and induces kidney tubule development in vitro
Authors: Itäranta Petri , Lin Yanfeng , Peräsaari Juha , Roël Giulietta , Destrée Olivier , Vainio Seppo 
Published: August 2002

AbstractSummary: The embryonic kidney is a classic developmental model system for studying inductive tissue interactions that govern organogenesis. We report here that Wnt‐6 is expressed in the ureter bud, and that cell lines expressing Wnt‐6 induce nephrogenesis in vitro. Wnt‐6 cells induce tubules with similar kinetics to spinal cord (SPC) and lead to induced expression of Pax2, Pax8, Sfrp2, and E‐cadherin genes, early markers of tubulogenesis. Moreover, Wnt‐6 signaling rescues tubulogenesis in mesenchyme separated from Wnt‐4 mutant embryos and leads to activation of Wnt‐4 transcription. Wnt‐6 also induces a secondary axis in early Xenopus embryos. We conclude that Wnt‐6 is a candidate for the ureter epithelium‐derived signal that leads to activation of kidney tubulogenesis via Wnt‐4. genesis 32:259–268, 2002. © 2002 Wiley‐Liss, Inc.
Characterization of a novel EGFP reporter mouse to monitor Cre recombination as demonstrated by a Tie2 Cre mouse line
Authors: Constien Rainer , Forde Anne , Liliensiek Birgit , Gröne Hermann‐Josef , Nawroth Peter , Hämmerling Günter , Arnold Bernd 
Published: August 2002

AbstractSummary: The use of the Cre/loxP system has greatly empowered the field of gene targeting. Here we describe the successful establishment of a novel knock‐in EGFP reporter mouse line to monitor Cre‐induced recombination in the vast majority of cell types. The value of this reporter mouse line is demonstrated by the use of a novel Tie2Cre transgenic mouse line that facilitates gene targeting in endothelial and hematopoietic cells. High efficiency of recombination was found in all endothelial cells and in the majority of hematopoietic cells but was absent in other tissues. Furthermore, in the second generation, the Tie2Cre mouse can be used to get 100% recombination of one allele, whilst allowing tissue specific in the second, therefore offering excellent efficiency. genesis 30:36–44, 2001. © 2001 Wiley‐Liss, Inc.
Modeling of HLA class II susceptibility to Type I diabetes reveals an effect associated with DPB1
Authors: Valdes Ana M. , Noble Janelle A. , Génin Emmanuelle , Clerget‐Darpoux Françoise , Erlich Henry A. , Thomson Glenys 
Published: August 2002

AbstractIn this report, we present evidence that the HLA class II DPB1 locus (or a locus with alleles in linkage disequilibrium with DPB1) contributes to Type I diabetes (IDDM) susceptibility in addition to the contribution of the HLA DR and DQ loci. The marker association segregation chi‐square (MASC) method, which fits both genotype frequency and affected sib‐pair identity‐by‐descent (IBD) distributions, was applied to 257 sib pairs affected with IDDM. Fitting DR‐DQ as the sole HLA susceptibility loci was strongly rejected. Next, we considered the DPB1 contribution to disease susceptibility. Published reports indicate a predisposing role for alleles DPB1*0301 and DPB1*0202, including our previous stratification analyses of association data on this sample. IDDM probands were stratified into those not carrying the alleles DPB1*0301 and DPB1*0202 (group DPB1‐A), and those carrying at least one copy of either allele (group DPB1‐B). Both groups of probands have almost identical frequencies of DR and DQ haplotypes but significantly different IBD distributions in the subset of families with probands who do not carry the highly predisposing DR3/DR4 genotype. In these data, DPB1 (or a locus in linkage disequilibrium), in addition to DR‐DQ, is involved in IDDM susceptibility and affects IBD in the HLA region. Addition of DPB1 in a genetic model of IDDM gives a better fit to the data than consideration of DR‐DQ alone. Our results are consistent with previous reports implicating DPB1 in IDDM susceptibility. Genet. Epidemiol. 21:212–223, 2001. © 2001 Wiley‐Liss, Inc.
Bayesian oligogenic analysis of quantitative and qualitative traits in general pedigrees
Authors: Uimari Pekka , Sillanpää Mikko J. 
Published: August 2002

AbstractA Bayesian method for multipoint oligogenic analysis of quantitative and qualitative traits is presented. This method can be applied to general pedigrees, which do not necessarily have to be “peelable” and can have large numbers of markers. The number of quantitative/qualitative trait loci (QTL), their map positions in the genome, and phenotypic effects (mode of inheritances) are all estimated simultaneously within the same framework. The summaries of the estimated parameters are based on the marginal posterior distributions that are obtained through Markov chain Monte Carlo (MCMC) methods. The method uses founder alleles together with segregation indicators in order to determine the genotypes of the trait loci of all individuals in the pedigree. To improve mixing properties of the sampler, we propose (1) joint sampling of map position and segregation indicators, (2) omitting data augmentation for untyped or uninformative markers (homozygous parent), and (3) updating several markers jointly within a single block. The performance of the method was tested with two replicate GAW10 data sets (considering two levels of available marker information). The results were concordant and similar to those presented earlier with other methods. These analyses clearly illustrate the utility and wide applicability of the method. Genet. Epidemiol. 21:224–242, 2001. © 2001 Wiley‐Liss, Inc.
Polyphase evolution and reaction sequence of compositional domains in metabasalt: a model based on local chemical equilibrium and metamorphic differentiation
Authors: Toóth T. M. , Grandjean V. , Engi M. 
Published: August 2002

AbstractEclogitic garnet amphibolite samples from the Southern Steep Belt of the Central Alps show evidence of several stages of metamorphic evolution and exhumation. A method for unravelling this evolution is presented and applied to these samples. It involves a combination of detailed petrographic analysis and microchemical characterization with quantitative models of the thermodynamically stable phase relations for specific compositional domains of each sample. Preserved mineral relics and textural evidence are compared to model predictions to identify the important irreversible reactions. The interpretation of the exhumation history is thus based on the consistency of a wide spectrum of observations with predicted phase diagrams, leading to robust reconstruction of a pressure–temperature (P–T) path even where the mineralogical relics in samples are insufficient, due to retrogression, to warrant application of multi‐equilibrium thermobarometric techniques.The formation of compositionally different domains in the metabasalt samples studied is attributed to prograde growth of porphyroblasts (e.g. garnet, plagioclase, zoisite) in the matrix, implying substantial metamorphic differentiation at the scale of a few millimetres. Chemical interaction among different domains during the subsequent P–T evolution is shown to have been very limited. This led to different reaction sequences during exhumation, in which relics preserved in different domains reflect a range of continually changing P–T conditions. For samples from a single outcrop, we deduce a Barrovian prograde path to eclogite facies (23 ± 3 kbar, 750 ± 50°C), followed by (rapid) decompression to 8 ± 1 kbar and 675 ± 25°C, and a final heating phase at similar pressures reaching 750 ± 40°C. This evolution is attributed to the Alpine cycle involving subduction→collision and slab breakoff→extrusion of tectonic fragments that make up the Southern Steep Belt of the Central Alps. Copyright © 2000 John Wiley & Sons, Ltd.
Expression of glial fibrillary acidic protein and glutamine synthetase by Müller cells after optic nerve damage and intravitreal application of brain‐derived neurotrophic factor
Authors: Chen Hao , Weber Arthur J. 
Published: August 2002

AbstractMüller glia play an important role in maintaining retinal homeostasis, and brain‐derived neurotrophic factor (BDNF) has proven to be an effective retinal ganglion cell (RGC) neuroprotectant following optic nerve injury. The goal of these studies was to investigate the relation between optic nerve injury and Müller cell activation, and to determine the extent to which BDNF affects the injury response of Müller cells. Using immunocytochemistry and Western blot analysis, temporal changes in the expression of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) were examined in rats after optic nerve crush alone, or in conjunction with an intravitreal injection of BDNF (5 μg). GFAP protein levels were normal at 1 day post‐crush, but increased ∼9‐fold by day 3 and remained elevated over the 2‐week period studied. Müller cell GS expression remained stable after optic nerve crush, but the protein showed a transient shift in its cellular distribution; during the initial 24‐h period post‐crush the GS protein appeared to translocate from the cell body to the inner and outer glial processes, and particularly to the basal endfeet located in the ganglion cell layer. BDNF alone, or in combination with optic nerve crush, did not have a significant effect on the expression of either GFAP or GS compared with the normal retina, or after optic nerve crush alone, respectively. The data indicate that although BDNF is a potent neuroprotectant in the vertebrate retina, it does not appear to have a significant influence on Müller cell expression of either GS or GFAP in response to optic nerve injury. GLIA 38:115–125, 2002. © 2002 Wiley‐Liss, Inc.
Long‐term modulation of glucose utilization by IL‐1α and TNF‐α in astrocytes: Na+ pump activity as a potential target via distinct signaling mechanisms
Authors: Véga Céline , Pellerin Luc , Dantzer Robert , Magistretti Pierre J. 
Published: August 2002

AbstractInterleukin‐1α (IL‐1α) and tumor necrosis factor‐α (TNF‐α) markedly stimulate glucose utilization in primary cultures of mouse cortical astrocytes. The mechanism that gives rise to this effect, which takes place several hours after application of cytokine, has remained unclear. Experiments were conducted to identify the major signaling cascades involved in the metabolic action of cytokine. First, the selective IL‐1 receptor antagonist (IL‐1ra) prevents the effect of IL‐1α on glucose utilization in a concentration‐dependent manner, whereas it has no effect on the action of TNF‐α. Then, using inhibitors of three classical signaling cascades known to be activated by cytokines, it appears that the PI3 kinase is essential for the effect of both IL‐1α and TNF‐α, whereas the action of IL‐1α also requires activation of the MAP kinase pathway. Participation of a phospholipase C‐dependent pathway does not appear critical for both IL‐1α and TNF‐α. Inhibition of NO synthase by L‐NAME did not prevent the metabolic response to both IL‐1α and TNF‐α, indicating that nitric oxide is probably not involved. In contrast, the Na+/K+ ATPase inhibitor ouabain prevents the IL‐1α‐ and TNF‐α‐stimulated 2‐deoxyglucose (2DG) uptake. When treatment of astrocytes with a cytokine was followed 24 h later by an acute application of glutamate, a synergistic enhancement in glucose utilization was observed. This effect was greatly reduced by ouabain. These data suggest that Na+ pump activity is a common target for both the long‐term metabolic action of cytokines promoted by the activation of distinct signaling pathways and the enhanced metabolic response to glutamate. GLIA 39:10–18, 2002. © 2002 Wiley‐Liss, Inc.
Distribution of P2X receptors on astrocytes in juvenile rat hippocampus
Authors: Kukley Maria , Barden Julian A. , Steinhäuser Christian , Jabs Ronald 
Published: August 2002

AbstractRecent evidence suggested that ATP acting via ionotropic (P2X) and metabotropic (P2Y) purinergic receptors might be involved in signaling between glial cells and within glial–neuronal networks. In contrast to their neuronal counterpart, the identity of P2X receptors in CNS glial cells is largely unknown. In the present study, antibodies recognizing the subunits P2X1–P2X7 were applied together with the astroglial marker S100β and nuclear labeling with Hoechst 33342 to investigate semiquantitatively the distribution of the whole set of P2X receptors in astrocytes of the juvenile rat hippocampus. Expression of P2X1–P2X4, P2X6, and P2X7 subunits was observed in astrocytes of various hippocampal subregions, but the cells were completely devoid of P2X5 protein. S100β‐positive cells expressing subunits P2X3–P2X7 occurred evenly in the different subfields, while P2X1‐ and P2X2‐positive astrocytes were distributed more heterogeneously. The staining pattern of P2X subunits also differed at the subcellular level. Antibodies against P2X2 and P2X4 labeled both astroglial cell bodies and processes. Immunoreactivity for P2X1 and P2X6 was mainly confined to somatic areas of S100β‐positive cells, whereas the subunit P2X3 was primarily localized along astroglial processes. Knowledge of the distribution of P2X receptors might provide a basis for a better understanding of their specific role in cell–cell signaling. GLIA 36:11–21, 2001. © 2001 Wiley‐Liss, Inc.
Bupropion SR in the naturalistic treatment of elderly patients with major depression
Authors: Steffens David C. , Doraiswamy P. Murali , McQuoid Douglas R. 
Published: August 2002

AbstractIntroductionBupropion immediate release (IR) and bupropion sustained release (SR) are frequently used to treat geriatric depression, as they have few cardiovascular, gastrointestinal and sexual adverse effects. We sought to examine the efficacy and dosing patterns of bupropion in a naturalistic cohort of elderly subjects with major depression (MD).Methods31 elderly ( > 60 years) patients with unipolar MD (DSM‐IV) who were enrolled in Duke's Mental Health Clinical Research Center for the Study of Depression in Later Life were prescribed bupropion SR or IR, alone or in combination with other antidepressant agents, for 12 weeks. Montgomery–Asberg depression rating scale (MADRS) scores and clinical global impression (CGI) severity scores were used to define response.Results74% (23/31) of the sample were responders (MADRS < 15) and 53% (16/30) achieved a partial (CGI = 2) or complete (CGI = 1) remission of MD at week 12. Among patients treated with bupropion SR monotherapy, the mean (range) maximal daily dose achieved was 240 mg (150–400 mg). Among those treated with bupropion IR, the mean (range) maximum daily dose achieved was 258 mg (150–450 mg). In subjects on monotherapy, 67% (10/15) of MD subjects were responders (MADRS < 15) and 50% (7/14) achieved full or partial remission. Response rates did not differ statistically among those with high and low medical comorbidity.ConclusionsIn this naturalistic 12‐week study, geriatric MD patients with high and low medical comorbidity responded well to bupropion and bupropion SR. In elderly patients, four to eight week acute treatment periods may be insufficient. Our findings suggest that nearly 50% of elderly depressed subjects at a tertiary center may need combination therapy over the course of their illness. Controlled randomized studies to establish the long‐term efficacy and optimal dose of the newer antidepressants in geriatric depression are urgently needed. Copyright © 2001 John Wiley & Sons, Ltd.
Neural basis for sentence comprehension: Grammatical and short‐term memory components
Authors: Cooke Ayanna , Zurif Edgar B. , DeVita Christian , Alsop David , Koenig Phyllis , Detre John , Gee James , Pinãngo Maria , Balogh Jennifer , Grossman Murray 
Published: August 2002

AbstractWe monitored regional cerebral activity with BOLD fMRI while subjects were presented written sentences differing in their grammatical structure (subject‐relative or object‐relative center‐embedded clauses) and their short‐term memory demands (short or long antecedent‐gap linkages). A core region of left posterior superior temporal cortex was recruited during all sentence conditions in comparison to a pseudofont baseline, suggesting that this area plays a central role in sustaining comprehension that is common to all sentences. Right posterior superior temporal cortex was recruited during sentences with long compared to short antecedent‐gap linkages regardless of grammatical structure, suggesting that this brain region supports passive short‐term memory during sentence comprehension. Recruitment of left inferior frontal cortex was most clearly associated with sentences that featured both an object‐relative clause and a long antecedent‐gap linkage, suggesting that this region supports the cognitive resources required to maintain long‐distance syntactic dependencies during the comprehension of grammatically complex sentences. Hum. Brain Mapping 15:80–94, 2001. © 2001 Wiley‐Liss, Inc.
2‐Polyfluoroacylcycloalkanones in reactions with selected phosphorus(III) compounds
Authors: Sevenard Dmitri V. , Lork Enno , Pashkevich Kazimir I. , Röschenthaler Gerd‐Volker 
Published: August 2002

AbstractThe reactivity of 2‐polyfluoroacylcycloalkanones and their O‐silylated derivatives towards phosphites and tris(trimethylsilyl)aminoiminophosphine has been investigated. From α‐polyfluoroalkyl substituted phosphonates, generated from tris(trimethylsilyl) phosphite and 1,3‐diketones, the respective phosphonic acids and their salts have been obtained. In one case, upon warming, a phosphonic acid underwent a ring closure to yield an oxaphospholene. 2‐Trifluoroacetylcycloalkanones and diethyl isocyanatophosphite furnished phosphoranes diastereospecifically, via addition of phosphorus at the trifluoroacetyl group and two additional heterocyclizations. Tris(trimethylsilyl)aminoiminophosphine formed very reactive trimethylsilylimino‐1,2λ5σ4‐phospholenes, which added hexafluoroacetone to give spirocyclic 1,3,2λ5σ5‐oxazaphosphetanes. The structures of the new compounds were determined by NMR spectroscopy and X‐ray single crystal analysis. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:97–107, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10001
Aminodiphenylphosphanes: Isotope‐induced chemical shifts 1Δ14/15N(31P), coupling constants 1J(31P,15N), and chemical shifts δ15N and δ31P
Authors: Contreras Rosalinda , Grevy Jean Michel , García‐Hernández Zureima , Göizado‐Rodriguez Marisol , Wrackmeyer Bernd 
Published: August 2002

AbstractA series of aminodiphenylphosphanes 1 [Ph2P‐N(H)tBu (a), ‐NEt2 (b), ‐NiPr2 (c)], 2 [Ph2P‐NHPh (a), ‐NH‐2‐pyridine (b), ‐NH‐3‐pyridine (c), ‐NH‐4‐pyridine (d), NH‐pyrimidine (e), NH‐2,6‐Me2‐C6H3 (f), NH‐3‐Me‐2‐pyridine (g)], 3 [Ph2P‐N(Me)Ph (a), ‐NPh2 (b)], and N‐pyrrolyldiphenylphosphane 4 (Ph2P‐NC4H4) was prepared and studied by NMR (1H, 13C, 31P, 15N NMR) spectroscopy. The isotope‐induced chemical shifts 1Δ14/15N(31P) were determined at natural abundance of 15N by using HEED INEPT experiments. A dependence of 1Δ14/15N(31P) on the substituents at nitrogen was found (alkyl < H < aryl; increasingly negative values). The magnitude and sign of the coupling constants 1J(31P,15N) (positive sign) are dominated by the presence of the lone pair of electrons at the phosphorus atom. The X‐ray structural analysis of 2b is reported, showing the presence of dimers owing to intermolecular hydrogen bridges in the solid state. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:542–550, 2001
Individual differences in spatial memory among aged rats are related to hippocampal PKCγ immunoreactivity
Authors: Colombo Paul J. , Gallagher Michela 
Published: August 2002

AbstractWe reported previously that the extent of spatial memory impairment among aged rats was correlated positively with levels of protein kinase Cγ in hippocampal homogenates measured by quantitative Western blotting (Colombo et al., 1997). In the current study, immunocytochemistry was used to test whether the relationship between elevated PKCγ and memory impairment among aged rats could be localized further within regions of the hippocampus. Six‐ and 24‐month‐old male Long‐Evans rats were first trained in the water maze on a standard place‐learning task and then trained 2 weeks later on a transfer task designed for rapid acquisition. In comparison with young rats, aged rats with impaired spatial memory had increased PKCγ‐immunoreactivity (PKCγ‐ir) in CA1 of the hippocampus, but not the dentate gyrus. In addition, PKCγ‐ir in CA1 was correlated positively with spatial memory impairment among aged rats on the standard place‐learning and the transfer training tasks. The current results are consistent with our previous report of PKCγ in hippocampal homogenates, and show further that the relationships between PKCγ‐ir and memory impairments among aged rats are most evident in area CA1. Thus age‐related impairments of spatial memory, as well as deficits in the flexible use of previously acquired information, may result from dysregulation of PKCγ. Hippocampus 2002;12:285–289. © 2002 Wiley‐Liss, Inc.