bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the gene expression changes induced by 17‐α‐ethynyl estradiol in the immature uterus/ovaries of the rat using high density oligonucleotide arrays
Authors: Naciff Jorge M. , Torontali Suzanne M. , Overmann Gary I. , Carr Gregory J. , Tiesman Jay P. , Daston George P. 
Published: April 2005

AbstractBACKGROUND: In a previous study, we determined the effects of 17‐α‐ethynyl estradiol (EE) on gene expression using microarrays that represented approximately 9,000 genes, which was the state of‐the‐art. Higher content arrays with almost double the number of genes have since become available. In order to better determine whether common sets of gene expression changes can be predictive of estrogenic activity, we have replicated the previous experiment using the more comprehensive microarray. METHODS: Immature 20‐day‐old Sprague‐Dawley rats were exposed to 0.1, 1, and 10 µg EE/kg/day ( subcutaneously [s.c.]), for four days, dosing from postnatal day (PND) 20–23). Changes in a more comprehensive expression level of 15,923 rat annotated genes and expressed sequence tags were evaluated on PND 24. RESULTS: By comparing the response of the treatment groups versus controls using various statistical parameters, we determined that the expression of 1,394 genes showed a significant change with respect to control (p≤0.0001), to at least one of the EE dosages. The tissues from animals exposed to 0.1 µg EE/kg/day showed changes in the expression of only 33 genes, whereas when they were exposed to 1 or 10 µg EE/kg/day, the expression of 409 and 548 genes was modified, respectively. A dose‐dependent analysis indicated that 592 genes showed a robust and significant response to EE exposure (increased or decreased). Our analysis confirmed the regulation of previously identified estrogen‐sensitive genes, and clearly identified novel mediators of estrogen actions, both in the uterus as well as in the ovary. CONCLUSIONS: This compendium of genes represents the largest compilation of estrogen‐responsive genes that has ever been identified for the immature uterus and ovary of any species, and can be used to generate testable hypothesis to improve the understanding of the molecular pathways associated with physiological and pathophysiological responses to exposure to chemicals with estrogenic properties. Birth Defects Res B 74:164–184, 2005. © 2005 Wiley‐Liss, Inc.
Recent innovations in tissue‐specific gene modifications in the mouse
Authors: Furuta Yasuhide , Behringer Richard R. 
Published: April 2005

AbstractAnnotating the functions of individual genes in in vivo contexts has become the primary task of mouse genetics in the postgenome era. In addition to conventional approaches using transgenic technologies and gene targeting, the recent development of conditional gene modification techniques has opened novel opportunities for elucidating gene function at the level of the whole mouse to individual tissues or cell types. Tissue‐specific gene modifications in the mouse have been made possible using site‐specific DNA recombinases and conditional alleles. Recent innovations in this basic technology have facilitated new types of experiments, revealing novel insights into mammalian embryology. In this review, we focus on these recent innovations and new technical issues that impact the success of these conditional gene modification approaches. Birth Defects Research (Part C) 75:43–57, 2005. © 2005 Wiley‐Liss, Inc.
Acute and late morbidity in the treatment of advanced bladder carcinoma with accelerated radiotherapy, carbogen, and nicotinamide
Authors: Hoskin Peter J. , Rojas Ana M. , Phillips Heather , Saunders Michele I. 
Published: April 2005

AbstractBACKGROUNDAccelerated radiotherapy combined with carbogen and nicotinamide (ARCON) to overcome tumor hypoxia and cell proliferation achieved high tumor control and survival in Phase II studies of patients with advanced head and neck and bladder carcinomas. Thus, morbidity and treatment outcomes from the latter study were analyzed to evaluate the therapeutic potential of ARCON.METHODSAcute and late morbidity was assessed in 105 patients with high‐grade superficial or muscle‐invasive bladder carcinoma who were given accelerated radiotherapy (50–55 grays in 4 weeks) with carbogen alone or with ARCON. Urinary dysfunction was scored based on daytime frequency, nocturia, incontinence, dysuria, hematuria, and urgency. Bowel morbidity was based on stool frequency and consistency, rectal discharge, blood loss, and medication. Endpoints for treatment outcome were overall survival, disease‐free survival, and locoregional control.RESULTSNearly all patients experienced reduced ability to retain urine beyond 2 hours, although 20–30% had almost normal function at night. Incidence of acute moderate or worse dysuria was 41% with ARCON and 56% with carbogen; 96% and 76% of patients, respectively, had bowel frequencies ≥ 3 times per day. By 10–12 weeks from the start of radiotherapy, acute reactions returned to baseline levels. At 3 years, the daytime frequency ≤ 2 times per hour was ≈ 75% in both arms. Incidence of severe hematuria (≤ 25%) and urinary urgency (≤ 16%) was much lower. No more than 6% of patients had severe bowel morbidity. With most assays, the differences between schedules were not significant either for acute or late morbidity. Local tumor control and survival rates at 3 years were 53% and 43%, respectively, for ARCON, similar to the rates for carbogen alone.CONCLUSIONSHistorical comparisons suggested no overt increase in normal tissue radiosensitivity when adding carbogen and nicotinamide. Although, for some endpoints, the incidence of late sequelae was higher than expected, overall morbidity was no worse than reported by others. The data indicated that ARCON could achieve a therapeutic gain in patients with advanced bladder carcinoma. A Phase III, randomized, multicenter trial is underway currently in the United Kingdom to evaluate these findings. Cancer 2005. © 2005 American Cancer Society.
Postnatal development of the cholinergic innervation in the dorsal hippocampus of rat: Quantitative light and electron microscopic immunocytochemical study
Authors: Aznavour Nicolas , Watkins Kenneth C. , Descarries Laurent 
Published: April 2005

AbstractCholine acetyltransferase (ChAT) immunocytochemistry was used to examine the distribution and ultrastructural features of the acetylcholine (ACh) innervation in the dorsal hippocampus of postnatal rat. The length of ChAT‐immunostained axons was measured and the number of ChAT‐immunostained varicosities counted, in each layer of CA1, CA3, and dentate gyrus, at postnatal ages P8, P16, and P32. At P8, an elaborate network of varicose ChAT‐immunostained axons was already visible. At P16, the laminar distribution of this network resembled that in the adult, but adult densities were reached only by P32. Between P8 and P32, the mean densities for the three regions increased from 8.4 to 14 meters of axons and 2.3 to 5.7 million varicosities per cubic millimeter of tissue. At the three postnatal ages, the ultrastructural features of ChAT‐immunostained axon varicosities from the strata pyramidale and radiatum of CA1 were similar between layers and comparable to those in adult, except for an increasing frequency of mitochondria (up to 41% at P32). The proportion of these profiles displaying a synaptic junction was equally low at all ages, indicating an average synaptic incidence of 7% for whole varicosities, as previously found in adult. The observed junctions were small, usually symmetrical, and made mostly with dendritic branches. These results demonstrate the precocious and rapid maturation of the hippocampal cholinergic innervation and reveal its largely asynaptic nature as soon as it is formed. They emphasize the remarkable growth capacities of individual ACh neurons and substantiate a role for diffuse transmission by ACh during hippocampal development. J. Comp. Neurol. 486:61–75, 2005. © 2005 Wiley‐Liss, Inc.
Afferent projections to pharynx and soft palate motoneurons: A light and electron microscopical tracing study in the cat
Authors: Boers Jose , Hulshoff Antoinette C. , de Weerd Henk , Mouton Leonora J. , Kuipers Rutger , Holstege Gert 
Published: April 2005

AbstractPharynx and soft palate are muscles for respiration, vocalization, swallowing, and vomiting. In cat, motoneurons innervating pharynx/soft palate are located in the dorsal group of the nucleus ambiguus (dgNA) in the medulla oblongata. In cat, dgNA is the only part of nucleus ambiguus that can be distinguished as a separate cell group, which makes it possible to study its afferent input. In two cats, WGA‐HRP injections in dgNA and surrounding tegmentum resulted in retrogradely labeled cells at several levels of the neuraxis. In 170 cases anterograde tracers were injected in areas in which the cells of origin were identified. Results demonstrate that dgNA afferents originate from the tegmentum dorsolateral to the superior olivary complex, medullary ventromedial tegmentum, caudal raphe nuclei, medullary lateral tegmental field, nucleus retroambiguus (NRA), and adjoining tegmentum, extending into the first cervical segment of the spinal cord. In order to determine whether periaqueductal gray (PAG) and parabrachial nuclei (PB) make synaptic contacts with dgNA, ultrastructural studies combined anterograde tracing from PAG, PB, and NRA with retrograde tracing of pharyngeal and soft palate motoneurons. The results showed that PB, but not PAG, projects to the dgNA and that NRA afferent synapses are three times as numerous as those from PB. The morphology of PB and NRA synapses is consistent with excitatory input. In conclusion, pharyngeal and soft palate motoneurons receive their afferents almost exclusively from the pontine and medullary tegmentum and first cervical spinal segment. J. Comp. Neurol. 486:18–38, 2005. © 2005 Wiley‐Liss, Inc.
Withdrawal from progesterone increases expression of α4, β1, and δ GABAA receptor subunits in neurons in the periaqueductal gray matter in female Wistar rats
Authors: Griffiths Jenny , Lovick Thelma 
Published: April 2005

AbstractPremenstrual dysphoric disorder (PMDD) shows comorbidity with other psychiatric conditions such as panic disorder (PD). The symptoms of both conditions are exacerbated during the late luteal phase of the menstrual cycle, when progesterone levels fall sharply. The present study investigated the effect of withdrawal from progesterone (PWD) on expression of α4, β1, and δ GABAA receptor subunits in neurons within the panic circuitry of the midbrain periaqueductal gray matter (PAG) in adult female Wistar rats. Immunostaining for α4, β1, and δ GABAA receptor subunits was present in neurons throughout the PAG in vehicle‐treated animals (VEH), in rats after 24 hours withdrawal from a progesterone dosing regime (PWD, 5 mg kg‐1 i.p. twice daily for 6 days), and in animals maintained on progesterone for 7 days (HP). Compared to HP and VEH animals, which did not differ significantly from each other, the number of immunostained neurons present in the PAG of PWD rats was significantly higher. The effect was most pronounced in the dorsolateral column of the PAG. The parallel changes in the three GABAA receptor subunits suggests that falling progesterone levels may be associated with expression of new receptors of the α4β1δ subtype. This could lead to functional changes in GABAergic transmission within the PAG. We suggest that changes in GABAA receptor‐mediated inhibitory tone in the PAG consequent to withdrawal from progesterone may contribute to the increased anxiety and susceptibility to panic seen during the late luteal phase of the menstrual cycle in PMDD and PD patients. J. Comp. Neurol. 486:89–97, 2005. © 2005 Wiley‐Liss, Inc.
Synthesis and characterization of dihydroxylammonium tetrachlorocuprate dihydrate crystals
Authors: Amirthaganesan G. , Kandhaswamy M. A. , Srinivasan V. 
Published: April 2005

AbstractA new hydroxylammonium compound, [(NH3OH)2CuCl4], was synthesized and its crystals were grown at room temperature by slow evaporation of aqueous solutions. The crystals were characterized through powder XRD, thermogravimetry (TG), differential thermal analysis (DTA), low temperature differential scanning calorimetric (DSC) and FTIR spectra. The X‐ray powder diffraction confirms the crystallinity of the compound. A fitting decomposition pattern of the compound was formulated based on the TG and thereby confirming the formation of the compound in the stoichiometric ratio. The thermal anomalies occurring in the low temperature DSC indicate successive phase transitions. The low temperature phase transitions are attributed to the ordering of [NH3OH]+ ions. While most of the phase transitions are of first order type, the one occurring at –126 °C is of second order. Two glass transitions occur when the compound was cooled between –157.9 and –136.9 °C. The characteristic vibration bands due to [NH3OH]+ and CuCl ions are observed in the IR spectra. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
FT‐IR spectroscopic and thermal studies on pure and impurity added calcium tartrate tetrahydrate crystals
Authors: Sahaya Shajan X. , Mahadevan C. 
Published: April 2005

AbstractPure and impurity (strontium) added calcium tartrate tetrahydrate single crystals were grown by the gel method. The FT‐IR spectra of these crystals were recorded in the wavenumber range 400–4000 cm–1. The thermograms of the grown crystals were recorded in the temperature range 50–900 °C. FT‐IR spectra reveals the presence of water molecules, O‐H bond, C‐O and carbonyl C=O bonds. The thermograms show that these crystals are thermally unstable and decompose into its oxide through many stages. DTA curve of the pure crystal shows three endothermic and one exothermic peaks. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Development of directional‐coupler‐type sensor for printed circuits
Authors: Kurokawa Satoru , Sato Toru 
Published: April 2005

AbstractAs a sensor capable of identifying the direction of the signal propagating along a transmission line on a printed circuit board and the mismatch of the characteristic impedances and its location, a directional‐coupler sensor in a stripline configuration is conceived. The tested sensor can measure the direction of the electromagnetic wave and the mismatch location of the characteristic impedances along the transmission line, which has been difficult to do with magnetic or electric sensors. In this paper, physical shape of the sensor with the best directionality is derived by FDTD numerical calculations. Such a sensor is fabricated and its effectiveness is demonstrated. It is confirmed that the tested sensor has a directivity of more than 25 dB at frequencies below 6 GHz, and of more than 17 dB at frequencies below 7 GHz. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 88(8): 41–49, 2005; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/ecja.10146
Impaired IL‐4 production by CD8+ T cells in NOD mice is related to a defect of c‐Maf binding to the IL‐4 promoter
Authors: Chen Xiao‐Ping , Falkner Dewayne H. , Morel Penelope A. 
Published: April 2005

AbstractCD8+ T cells play an important role in the induction of the autoimmune response in non‐obese diabetic (NOD) mice. Here we describe abnormalities in the control of cytokine production by NOD CD8+ T cells. NOD CD8+ T cells had an increased propensity to produce IFN‐γ upon TCR activation, in both adult and 2‐week‐old mice. NOD CD8+ T cells had a reduced capacity to produce IL‐4 in type 2 conditions compared to CD8+ T cells from the diabetes‐resistant strains BALB/c and C57BL/6. Both GATA‐3 and c‐Maf, two positive transactivators for IL‐4 gene expression, were expressed in type 2 conditions at comparable levels in NOD CD8+ T cells. The GATA‐3 was functional since normal levels of IL‐5 were produced and the IL‐4 promoter was hyperacetylated in NOD CD8+ T cells. In contrast, c‐Maf failed to bind to its responsive element as determined by chromatin immunoprecipitation (ChIP) assay. These results suggest that NOD CD8+ T cells possess an increased propensity to produce IFN‐γ and impaired c‐Maf‐dependent DNA binding activities in vivo that lead to reduced IL‐4 production following TCR activation. These defects may facilitate the development of the autoimmune response by inducing an overall type 1‐biased immune response in NOD mice.
Toll‐like receptor‐dependent activation of several human blood cell types by protamine‐condensed mRNA
Authors: Scheel Birgit , Teufel Regina , Probst Jochen , Carralot Jean‐Philippe , Geginat Jens , Radsak Markus , Jarrossay David , Wagner Hermann , Jung Günther , Rammensee Hans‐Georg , Hoerr Ingmar , Pascolo Steve 
Published: April 2005

AbstractWe reported that RNA condensed on protamine is protected from RNase‐mediated degradation and can be used for vaccination. Here, we show that such complexes are also danger signals that activate mouse cells through a MyD88‐dependent pathway. Moreover, mRNA‐protamine complexes stimulate human blood cells. They strongly activate DC and monocytes, leading to TNF‐α and IFN‐α secretion. In addition, protamine‐RNA complexes directly activate B cells, NK cells and granulocytes. The detailed analysis of the activated cell types, the study of the cytokines released from PBMC cultured with protamine‐RNA complexes and recently published results suggest that TLR‐7 and TLR‐8 may be involved in the recognition of protamine‐stabilized RNA. Our data indicate that protamine‐stabilized RNA, which may be similar to RNA condensed in the nucleocapsids of RNA viruses, is a strong danger signal. Thus, similarly to plasmid DNA, protamine‐RNA combines antigen production and non‐specific immunostimulation. The studies presented here explain the capacity of protamine‐RNA to act as a vaccine, and pave the way towards the development of safe and efficient mRNA‐based immunotherapies.
Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice
Authors: Miyazaki Tatsuhiko , Ono Masao , Qu Wei‐Min , Zhang Ming‐Cai , Mori Shiro , Nakatsuru Shuichi , Nakamura Yusuke , Sawasaki Tatsuya , Endo Yaeta , Nose Masato 
Published: April 2005

AbstractPotentially, autoimmune diseases develop from a combination of multiple genes with allelic polymorphisms. An MRL/Mp‐Faslpr/lpr (MRL/lpr) strain of mice develops autoimmune diseases, including lupus nephritis, but another lpr strain, C3H/HeJ‐Faslpr/lpr (C3H/lpr) does not. This indicates that MRL polymorphic genes are involved in the development of the diseases. By quantitative trait loci (QTL) analysis using 527 of the (MRL/lpr × C3H/lpr)F2 mice, we identified a novel locus for susceptibility to lupus nephritis at map position D5Mit115 on chromosome 5, the same alias of the osteopontin (Opn) gene (LOD score =4.0), susceptible in the MRL allele. In functional analyses of the MRL and C3H Opn alleles using synthetic osteopontin (OPN) made with a new method “cell‐free system” with wheat germ ribosomes, the MRL‐OPN induced higher expression and production of immunoglobulins as well as cytokines including TNF‐α, IL‐1β and IFN‐γ in splenocytes and/or macrophages than that of the C3H allele. These findings suggest that allelic polymorphism of OPN causes the functional differences in antibody production and macrophage activation between MRL and C3H strains, possibly involved in the development of lupus nephritis.
Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis
Authors: Manzo Antonio , Paoletti Samantha , Carulli Maresa , Blades Mark C. , Barone Francesca , Yanni Ghada , FitzGerald Oliver , Bresnihan Barry , Caporali Roberto , Montecucco Carlomaurizio , Uguccioni Mariagrazia , Pitzalis Costantino 
Published: April 2005

AbstractCXCL13 and CCL21 have been functionally implicated in lymphoid tissue organization both in the upstream phases of lymphoid tissue embryogenesis and in ectopic lymphoid neogenesis in transgenic mice. Here, we analyzed the relationship between CXCL13 and CCL21 production and lymphoid tissue organization in rheumatoid synovitis as a model of a naturally occurring ectopic lymphoneogenesis. Through systematic analysis of mRNA and protein expression, we defined the microanatomical relationship between CXCL13 and CCL21 in progressive aggregational and structural phases of synovial inflammatory infiltrate. We provide the first direct in situ evidence that production of CXCL13 and CCL21 (rather than simply protein binding) is associated with inflammatory lymphoid tissue formation and development with the demonstration, in organized aggregates, of a secondary lymphoid organ‐like compartmentalization and vascular association. Notably, the presence of CXCL13 and CCL21 (protein and mRNA) was also demonstrated in non‐organized clusters and minor aggregational stages, providing evidence that their induction can take place independently and possibly upstream of T‐B compartmentalization, CD21+ follicular dendritic cell network differentiation and germinal center formation. Our data support the concept that, under inflammatory conditions, CXCL13 and CCL21 participate in lymphoid tissue microanatomical organization, attempting to recapitulate, in an aberrant lymphoid neogenetic process, their homeostatic and morphogenetic physiologic functions.
Humoral immune response to citrullinated collagen type II determinants in early rheumatoid arthritis
Authors: Burkhardt Harald , Sehnert Bettina , Bockermann Robert , Engström Åke , Kalden Jochen R. , Holmdahl Rikard 
Published: April 2005

AbstractCollagen type II (CII) is a relevant joint‐specific autoantigen in the pathogenesis of rheumatoid arthritis (RA). Whereas the reasons for the breakage of self tolerance to this major cartilage component are still enigmatic, T cell responses to glycosylated CII determinants in RA patients indicate that post‐translational modifications play a role. Since the conversion of arginine into citrulline by peptidylarginine deiminases (PAD) in some non‐joint‐specific antigens such as filaggrin or fibrin has been shown to give rise to RA‐specific humoral immune responses, we investigated whether PAD modification of cartilage‐specific CII might affect its recognition by circulating autoantibodies in early RA. In vitro treatment with purified PAD led to arginine deimination of native CII or of synthetic CII peptides as evidenced by amino acid analysis. The citrullination resulted in modified recognition of the immunodominant CII epitope C1III (amino acid residues 359–369) by murine and human antibodies. In a cohort of early RA patients (n=286), IgG antibodies directed toward a synthetic citrullinated C1III peptide (citC1III‐P) were detectable with a prevalence of 40.4%. The partial autoantibody cross‐reactivity between citC1III‐P and citrullinated peptides mimicking epitopes of the cytoskeletal autoantigen filaggrin suggests that autoimmunity to cartilage‐specific modified self might be a critical intermediate bridging recognition of PAD‐modified extra‐articular autoantigens with the disruption of tolerance to native cartilage constituents.