bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nurr1 co‐localizes with EphB1 receptors in the developing ventral midbrain, and its expression is enhanced by the EphB1 ligand, ephrinB2
Authors: Calò Laura , Spillantini MariaGrazia , Nicoletti F. , Allen Nicholas D. 
Published: January 2005

AbstractBoth ephrins and the transcription factor, Nurr1, are critically involved in CNS development and, particularly, in the ontogenesis of the nigro‐striatal system. Here we examined whether the ephrin receptor, EphB1, and Nurr1 share a similar expression pattern in the embryonic brain and whether expression of Nurr1 is under the control of EphB1 activation. The transcripts of EphB1 receptor and Nurr1 showed a similar pattern of expression in the ventral midbrain of mice at early stages of embryonic development (E11.5 and E12.5). At later stages (E15.5), only Nurr1 mRNA could still be detected in significant amounts in the A9–A10 regions of the ventral midbrain, whereas the two transcripts still showed a similar pattern of expression in discrete regions of the hindbrain. To examine whether activation of EphB1 receptor could induce the expression of Nurr1 in the ventral midbrain, we applied the EphB1 ligand, ephrinB2, to explants of embryonic mouse ventral midbrain. Low concentrations of clustered ephrinB2 (0.25 µg/mL) enhanced Nurr1 mRNA and protein levels, whereas higher concentrations were inactive. We conclude that activation of EphB1 receptors by appropriate concentrations of its ligand ephrinB2 might contribute to the acquisition of a dopaminergic fate in developing midbrain ventral neurones.
Diminished Akt phosphorylation in neurons lacking glutathione peroxidase‐1 (Gpx1) leads to increased susceptibility to oxidative stress‐induced cell death
Authors: Taylor Juliet M. , Ali Uǧur , Iannello Rocco C. , Hertzog Paul , Crack Peter J. 
Published: January 2005

AbstractWe have previously identified an increased susceptibility of glutathione peroxidase‐1 (Gpx1)–/– mice to neuronal apoptosis following mid‐cerebral artery (MCA) occlusion. This study was designed to elucidate the mechanisms involved in elevated neuronal cell death arising from an altered endogenous oxidant state. This was addressed in both an in vitro and in vivo model of oxidative stress in the form of exogenous H2O2 and cerebral ischaemia, respectively. Increased levels of cell death were detected in primary neurons lacking Gpx1 following the addition of exogenous H2O2. This increased apoptosis correlated with a down‐regulation in the activation of the phospho‐inositide 3‐kinase [PI(3)K]–Akt survival pathway. The importance of this pathway in protecting against H2O2‐induced cell death was highlighted by the increased susceptibility of wildtype neurons to apoptosis when treated with the PI(3)K inhibitor, LY294002. The Gpx1–/– mice also demonstrated elevated neuronal cell death following MCA occlusion. Although Akt phosphorylation was detected in the Gpx1–/– brains, activation was not seen in later reperfusion events, as demonstrated in wildtype brains. Previous studies have highlighted the importance of Akt phosphorylation in protecting against neuronal cell death following cerebral ischaemia–reperfusion. Our results suggest that the increased susceptibility of Gpx1–/– neurons to H2O2‐induced apoptosis and neuronal cell death in vivo following cerebral ischaemia–reperfusion injury can be attributed in part to diminished activation of Akt. Perturbations in key anti‐apoptotic mechanisms as a result of an altered redox state may have implications in the study of oxidative stress‐mediated neuropathologies.
Brain response to traumatic brain injury in wild‐type and interleukin‐6 knockout mice: a microarray analysis
Authors: Poulsen Christian Bjørn , Penkowa Milena , Borup Rehannah , Nielsen Finn Cilius , Cáceres Mario , Quintana Albert , Molinero Amalia , Carrasco Javier , Giralt Mercedes , Hidalgo Juan 
Published: January 2005

AbstractTraumatic injury to the brain is one of the leading causes of injury‐related death or disability. Brain response to injury is orchestrated by cytokines, such as interleukin (IL)‐6, but the full repertoire of responses involved is not well known. We here report the results obtained with microarrays in wild‐type and IL‐6 knockout mice subjected to a cryolesion of the somatosensorial cortex and killed at 0, 1, 4, 8 and 16 days post‐lesion. Overall gene expression was analyzed by using Affymetrix genechips/oligonucleotide arrays with ∼12 400 probe sets corresponding to ∼10 000 different murine genes (MG_U74Av2). A robust, conventional statistical method (two‐way anova) was employed to select the genes significantly affected. An orderly pattern of gene responses was clearly detected, with genes being up‐ or down‐regulated at specific timings consistent with the processes involved in the initial tissue injury and later regeneration of the parenchyma. IL‐6 deficiency showed a dramatic effect in the expression of many genes, especially in the 1 day post‐lesion timing, which presumably underlies the poor capacity of IL‐6 knockout mice to cope with brain damage. The results highlight the importance of IL‐6 controlling the response of the brain to injury as well as the suitability of microarrays for identifying specific targets worthy of further study.
Neuronal precursor‐specific activity of a human doublecortin regulatory sequence
Authors: Karl Claudia , Couillard‐Despres Sebastien , Prang Peter , Munding Matthias , Kilb Werner , Brigadski Tanja , Plötz Sonja , Mages Wolfgang , Luhmann Heiko , Winkler Jürgen , Bogdahn Ulrich , Aigner Ludwig 
Published: January 2005

AbstractThe doublecortin (DCX) gene encodes a 40‐kDa microtubule‐associated protein specifically expressed in neuronal precursors of the developing and adult CNS. Due to its specific expression pattern, attention was drawn to DCX as a marker for neuronal precursors and neurogenesis, thereby underscoring the importance of its promoter identification and promoter analysis. Here, we analysed the human DCX regulatory sequence and confined it to a 3.5‐kb fragment upstream of the ATG start codon. We demonstrate by transient transfection experiments that this fragment is sufficient and specific to drive expression of reporter genes in embryonic and adult neuronal precursors. The activity of this regulatory fragment overlapped with the expression of endogenous DCX and with the young neuronal markers class III β‐tubulin isotype and microtubule‐associated protein Map2ab but not with glial or oligodendroglial markers. Electrophysiological data further confirmed the immature neuronal nature of these cells. Deletions within the 3.5‐kb region demonstrated the relevance of specific regions containing transcription factor‐binding sites. Moreover, application of neurogenesis‐related growth factors in the neuronal precursor cultures suggested the lack of direct signalling of these factors on the DCX promoter construct.
Neuroadaptations of total levels of adenylate cyclase, protein kinase A, tyrosine hydroxylase, cdk5 and neurofilaments in the nucleus accumbens and ventral tegmental area do not correlate with expression of sensitized or tolerant locomotor responses to cocaine
Authors: Hope B. T. , Crombag H. S. , Jedynak J. P. , Wise R. A. 
Published: January 2005

AbstractNeuroadaptations induced by high‐dose cocaine treatment have been hypothesized to persist after the cessation of drug treatment and mediate the expression of sensitization and tolerance to cocaine. We looked for evidence of these neuroadaptations in rats receiving more modest behaviorally effective cocaine treatments. Rats were exposed to either a sensitizing regimen of seven once‐daily injections of 15 mg/kg cocaine or a tolerance‐producing regimen involving a continuous infusion of the same daily dose. We assessed enzyme activity levels of protein kinase A and adenylate cyclase, and protein levels of tyrosine hydroxylase, cdk5 and neurofilaments in the nucleus accumbens and ventral tegmental area. Only protein kinase A activity levels were altered by cocaine treatment, but this alteration persisted for only 7 days, whereas a sensitized locomotor response was still evident at 21 days. Although behavioral tolerance to cocaine was seen the day after the termination of treatment, none of the molecular measures was altered on this or any other day. Thus, although increased protein kinase A activity can temporarily modulate sensitized responses to cocaine, alterations in total levels of the molecules assessed in our study do not correlate with the expression of sensitized or tolerant locomotor responses to cocaine.
The role of tissue plasminogen activator in methamphetamine‐related reward and sensitization
Authors: Nagai Taku , Noda Yukihiro , Ishikawa Kazuhiro , Miyamoto Yoshiaki , Yoshimura Masako , Ito Mina , Takayanagi Masanori , Takuma Kazuhiro , Yamada Kiyofumi , Nabeshima Toshitaka 
Published: January 2005

AbstractIn the central nervous system, tissue plasminogen activator (tPA) plays a role in synaptic plasticity and remodeling. Our recent study has suggested that tPA participates in the rewarding effects of morphine by regulating dopamine release. In this study, we investigated the role of tPA in methamphetamine (METH)‐related reward and sensitization. Repeated METH treatment dose‐dependently induced tPA mRNA expression in the frontal cortex, nucleus accumbens, striatum and hippocampus, whereas single METH treatment did not affect tPA mRNA expression in these brain areas. The METH‐induced increase in tPA mRNA expression in the nucleus accumbens was completely inhibited by pre‐treatment with R(+)‐SCH23390 and raclopride, dopamine D1 and D2 receptor antagonists, respectively. In addition, repeated METH treatment increased tPA activity in the nucleus accumbens. There was no difference in METH‐induced hyperlocomotion between wild‐type and tPA‐deficient (tPA–/–) mice. On the other hand, METH‐induced conditioned place preference and behavioral sensitization after repeated METH treatment were significantly reduced in tPA–/– mice compared with wild‐type mice. The defect of behavioral sensitization in tPA–/– mice was reversed by microinjections of exogenous tPA into the nucleus accumbens. Our findings suggest that tPA is involved in the rewarding effects as well as the sensitization of the locomotor‐stimulating effect of METH.
The Impact of E‐Replenishment Strategy on Make‐to‐Order Supply Chain Performance
Authors: Robinson E. Powell , Sahin Funda , Gao Li‐Lian 
Published: January 2005

ABSTRACTThis research investigates the impact of electronic replenishment strategy on the operational activities and performance of a two‐stage make‐to‐order supply chain. We develop simulation‐based rolling schedule procedures that link the replenishment processes of the channel members and apply them in an experimental analysis to study manual, semi‐automated, and fully automated e‐replenishment strategies in decentralized and coordinated decision‐making supply chain structures. The average operational cost reductions for moving from a manual‐based system to a fully automated system are 19.6, 29.5, and 12.5%, respectively, for traditional decentralized, decentralized with information sharing, and coordinated supply chain structures. The savings are neither equally distributed among participants, nor consistent across supply chain structures. As expected, for the fully coordinated system, total costs monotonically decrease with higher levels of automation. However, for the two decentralized structures, under which most firms operate today, counter‐intuitive findings reveal that the unilateral application of e‐procurement technology by the buyer may lower his purchasing costs, but increase the seller's and system's costs. The exact nature of the relationship is determined by the channel's operational flexibility. Broader results indicate that while the potential economic benefit of e‐replenishment in a decentralized system is substantial, greater operational improvements maybe possible through supply chain coordination.
Dynamic Changes in the QT–R‐R Relationship during Head‐Up Tilt Test in Patients with Vasovagal Syncope
Authors: Mizumaki Koichi , Fujiki Akira , Sakabe Masao , Nishida Kunihiro , Sugao Masataka , Tsuneda Takayuki , Nagasawa Hidehiko , Inoue Hiroshi 
Published: January 2005

Background: QT interval is influenced by preceding R‐R intervals and autonomic nervous tone. Changes in QT intervals during vasovagal reflex might reflect autonomic modulation of ventricular repolarization; however, this issue has not been fully elucidated. This study aimed to evaluate dynamic response of QT interval to transient changes in R‐R interval during vasovagal syncope (VVS) induced by head‐up tilt test. Methods: Eighteen patients with VVS and 18 age‐and sex‐matched controls were studied. All patients with VVS had a positive mixed‐type response to head‐up tilt and all controls had a negative response. CM5‐lead digital electrocardiogram (ECG) was recorded and QT intervals were analyzed using Holter ECG analyzer. Using scatter plots of consecutive QT and the preceding R‐R intervals, QT–R‐R relations during tilt‐up and tilt‐back or during vasovagal reflex were independently fitted to an exponential curve: QT (second) = A + B × exp[k × R‐R (second)]. Results: During the tilt‐up, A, B, and k did not differ between patients with VVS and controls. During the tilt back, k showed equivalent positive value compared to the tilt‐up (4.1 ± 1.3 vs −4.6 ± 0.9) in controls. However, k remained negative (−1.3 ± 1.5) during vasovagal reflex in patients with VVS. In six patients, in whom metoprolol was effective in eliminating VVS, QT–R‐R relationship during the tilt‐back became similar to that in controls. Conclusions: In patients with VVS, hysteresis of the QT–R‐R relation is similarly shown during tilt‐up as in controls, whereas this hysteresis is no longer evident and failure of QT prolongation is observed during VVS.
Microarray gene expression profiling of cell lines from primary and metastatic tongue squamous cell carcinoma: possible insights from emerging technology
Authors: Vigneswaran Nadarajah , Wu Jean , Sacks Peter , Gilcrease Michael , Zacharias Wolfgang 
Published: January 2005

Background:  To identify common gene expression patterns among two uniquely matched pairs of primary and metastatic oral squamous cell carcinoma (OSCC) cell lines derived from the same two patient donors.Methods:  Two pairs of cell lines derived from the primary tumors and lymph node metastases of the same two patients were used to obtain microarray‐based gene expression profiles. Reverse transcriptase‐polymerase chain reaction and immunohistochemistry were used to confirm observed changes for some of the candidate genes.Results:  Approximately 50% of the genes profiled were expressed in all four cell lines. Cluster analysis identified a group of 17 genes whose expression correlated inversely with metastatic progression. Only 10 common genes were differentially expressed in both pairs of primary and metastatic cells. A group of 28 highly expressed genes was common for both metastatic cell lines, among them some of the known metastasis‐related genes such as laminin receptor, thymosin β‐4 and β‐10 and metallopanstimulin.Conclusions:  Groups of presumed metastasis‐related genes are highly heterogeneous and vary significantly between the two patients. Thus, it is unlikely that the metastatic phenotype of these OSCC cells is acquired by de‐regulation of a single gene or a group of few genes. Most likely, multiple combinations of differentially expressed genes are involved in facilitating metastatic spread of these oral carcinoma cell lines.
Cytoplasmic expression of E‐cadherin and β‐Catenin correlated with LOH and hypermethylation of the APC gene in oral squamous cell carcinomas
Authors: Gao Shan , Eiberg Hans , Krogdahl Annelise , Liu Chung‐Ji , Sørensen Jens Ahm 
Published: January 2005

Background:  Inactivation of the adenomatous polyposis coli (APC) gene results in accumulation and translocation of β‐Catenin, which are important for malignant development. The aim of the present study is to investigate the possible role of APC/β‐Catenin pathway in oral squamous cell carcinomas.Methods:  The DNA from 34 patients was examined for loss of heterozygosity (LOH) at two markers surrounding the APC, and for hypermethylation of the APC promoter by using methylation‐specific polymerase chain reaction (MS‐PCR). Fifteen of 34 samples were stained immunohistochemically to show the expression of E‐cadherin and β‐Catenin.Results:  We found that cytoplasmic rather than membrane staining of E‐cadherin and β‐Catenin was a prominent aberrant tumour‐related alteration, and that this expression was mainly present in moderately and poorly differentiated tumours. LOH and hypermethylation of the APC promoter was found in four of 31 and five of 34 carcinoma samples, respectively. Four of five cases presenting LOH/hypermethylation showed cytoplasmic expression of E‐cadherin and β‐Catenin by immunohistochemical (IHC) staining.Conclusion:  The present results indicate that LOH at the APC locus or hypermethylation of the APC promoter 1a may lead to free β‐Catenin accumulation in cytoplasm of oral carcinoma cells and thereby to oral malignant progression.
Influences of angiogenesis and lymphangiogenesis on cancerous invasion in experimentally induced tongue carcinoma
Authors: Nakaya Hiromitsu , Kawashiri Shuichi , Tanaka Akira , Noguchi Natsuyo , Kato Koroku , Hase Takashi , Yamamoto Etsuhide 
Published: January 2005

Background:  Although it is clear that dissemination via the blood system involves angiogenesis, it is uncertain whether tumors also induce lymphangiogenesis or simply invade existing peritumoral vessels. The purpose of this study was to elucidate changes in tumor blood and lymph vessels in cases involving the invasion of squamous cell carcinoma in the oral cavity, and its significance. Blood and lymph vessels densities in tongue carcinomas induced in hamsters were investigated.Methods:  Tongue cancer was induced by abrading the right margin of the tongue of each hamster with an endodontic barbed broach and subsequently applying 1.0% 9,10‐dimenthl‐1,2‐benzanthracene (DMBA) dissolved in acetone, three times a week, at the same site. Fresh frozen sections were prepared and blood vessels stained blue by perfusion with Coomassie Brilliant Blue and lymph vessels stained brown for 5′‐nucleotidase. The effects on the blood vessels and lymph vessels were observed.Results:  The results showed that blood and lymph vessel densities were greater in the advanced carcinoma tissues than in normal tissue. These were compared in terms of the mode of cancer invasion. As tumor invasion progressed, the blood vessel density decreased but lymph vessel density tended to be higher in high‐degree tumor invasion than in low‐degree tumor invasion. The expression of vascular endothelial growth factor‐C was seen more frequently as tumor invasion progressed.Conclusions:  The present findings indicated that angiogenesis and lymphangiogenesis are affected by cancerous invasion.
Raised keratinocyte growth factor‐1 expression in oral submucous fibrosis in vivo and upregulated by arecoline in human buccal mucosal fibroblasts in vitro
Authors: Tsai Chung‐Hung , Yang Shun‐Fa , Chen Yi‐Juai , Chou Ming‐Yung , Chang Yu‐Chao 
Published: January 2005

Background:  Keratinocyte growth factor‐1 (KGF‐1) is the seventh member of the fibroblast growth factor family. KGF‐1 is produced by mesenchymal cells such as fibroblasts and upregulated in a variety of hyperplastic tissues. Currently, there is limited information about the regulation of KGF‐1 expression in areca quid‐associated oral submucous fibrosis (OSF). The aim of the study was to compare KGF‐1 expression in normal human buccal mucosa and OSF specimens and further to explore the potential mechanism that may lead to induce KGF‐1 expression.Methods:  The expression of KGF‐1 from fibroblasts cultured from OSF and normal buccal mucosa were using reverse‐transcriptase polymerase chain reaction and enzyme‐linked immunosorbent assay. In addition, arecoline, a major areca nut alkaloid, was challenged to normal buccal mucosa fibroblasts (BMFs) to elucidate whether KGF‐1 expression could affect by arecoline. Furthermore, 25 OSF specimens and six normal buccal mucosa specimens were examined by immunohistochemistry.Results:  Fibroblasts derived from OSF were found to exhibit higher KGF‐1 expression than BMFs both in mRNA and protein levels (P < 0.05). In addition, upregulation of KGF‐1 mRNA gene and protein expression were found in BMFs stimulated by arecoline (P < 0.05). From the results of immunohistochemistry, KGF‐1 expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, endothelial cells, inflammatory cells, and epithelial cells.Conclusions:  Taken together, these results suggest that KGF‐1 expression is significantly upregulated in OSF tissues from areca quid chewers and arecoline may be responsible for the enhanced KGF‐1 expression in vivo.
Sentinel lymph nodes in cancer of the oral cavity – isolated tumour cells
Authors: Thomsen Jørn Bo , Sørensen Jens Ahm , Krogdahl Annelise 
Published: January 2005

Background:  Sentinel lymph node biopsy, step sectioning and immunohistochemistry have changed detection of tumour deposits. Isolated tumour cells (ITC) are detected more frequently than earlier because of a changed level of detection.Methods:  A total of 108 sentinel lymph nodes from 30 patients with T1/T2 cN0 oral cancer were re‐classified histologically to find possible ITC and to describe technical pitfalls.Results:  Primarily we found metastatic spread in 12 of 108 sentinel lymph nodes: five macrometastasis and seven micrometastasis. After re‐classification, we found seven lymph nodes with macrometastasis, five with micrometastasis and two with ITC.Conclusion:  The ITC are probably precursors of micrometastasis waiting to grow and should be treated as such. Benign inclusions and dendritic cells did not cause problems, but can mimic ITC.
Conservative treatment of paediatric mandibular fracture by the use of orthodontic appliance and rubber elastics: report of a case
Authors: Gawelin Petter J. E. , Thor Andreas L. I. 
Published: January 2005

Abstract –  Treatment principles of paediatric mandibular fractures may differ from the treatment of the adult population in that a conservative approach is in most cases advocated before the use of internal rigid fixation with plates and screws. This is because of a relative high risk of disturbed facial skeletal growth and risk of damaging unerupted teeth. Knowledge of conservative treatment options is essential in order to minimize these risks and one option is presented in this paper.This case report describes a 5‐year‐old girl that sustained an open fracture of the mandible and who was successfully treated by the means of applying orthodontic brackets and an arch bar combined with ligatures and rubber elastics.