bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of transendoscopic miniature ultrasonic probe for chemoradiotherapy outcome in patients with locally advanced esophageal cancer
Authors: Iwase Hiroaki , Shimada Masaaki , Tsuzuki Tomoyuki , Doi Reiko , Okeya Masayuki , Kobayashi Keiko 
Published: March 2005

Background: Assessment of the response of esophageal cancer to chemoradiotherapy is difficult. We investigated the value of a transendoscopic miniature ultrasonic probe (USP) in assessing response to chemoradiotherapy in patients with locally advanced esophageal cancer.Methods: A total of 33 patients were entered in this prospective study. Response to treatment was evaluated according to World Health Organization criteria. According to the sonographic image, complete response (CR) of the primary lesion was divided into two subcategories: confirmed CR (cCR) and unconfirmed CR (uCR).Results: Initial sonographic criteria for evaluating tumor depth and lymph nodes in the 33 patients before therapy showed two cases of T2N0, four of T3N0, 15 of T3N1, four of T4N0, and eight of T4N1. Following chemoradiotherapy, CR was obtained in 18 (54.5%): seven cCR and 11 uCR. Eleven were partial response (PR) (33.3%), while three were stable disease (SD) and one was progressive disease (PD). High frequency USP (20 MHz) was able to detect tumor disappearance and restoration of the esophageal wall. One‐year survival rates among CR (cCR + uCR), PR and SD + PD were 100%, 70% and 0%, respectively. A significant difference in survival was evident among CR, PR and SD + PD (P < 0.001). Three‐year survival rates between cCR and uCR were 100% and 40%, respectively. A significant difference in survival was evident between cCR and uCR (P < 0.001). In seven cases of uCR, local recurrence and distant metastasis appeared within 1 year, and five died of disease progression. Not one cCR case has relapsed.Conclusion: USP, which can be accomplished with a standard endoscopy, including biopsy, in one procedure, is a useful method for objectively assessing the response to chemoradiotherapy in patients with locally advanced esophageal cancer.
A new type of hemoclip device
Authors: Watanabe Kenichi , Itoh Akemi , Kobayashi Kenji , Suzuki Takayoshi , Shirai Takayuki , Mine Tetsuya 
Published: March 2005

Background: There are many endoscopic techniques for hemostasis of non‐variceal upper GI bleeding. Endoscopic hemoclip placement is one of the most important techniques. A rotatable clip‐fixing device developed by Olympus Co. (Tokyo, Japan) has come into widespread use in Japan. However, it involves a number of problems, such as requirement of skill for attachment and it is time‐consuming.Materials: We developed a new type of hemoclip device with collaboration with Olympus Co.Results: We explain the new type of hemoclip device and how to use it. Finally, we examine the convenience of the new type of hemoclip compared with previous devices.Conclusion: Hemoclip placement for bleeding of GI tract seems to be very convenient now and may become common in the world in the future.
Investigation of PKC isoform‐specific translocation and targeting of the current of the late afterhyperpolarizing potential of myenteric AH neurons
Authors: Nguyen Trung V. , Poole Daniel P. , Harvey John R. , Stebbing Martin J. , Furness John B. 
Published: March 2005

AbstractAH neurons in the enteric nervous system play an essential role in initiating intestinal reflexes and factors that control AH neuron excitability therefore influence the state of the digestive system. Prominent afterhyperpolarizations that follow action potentials in these neurons strongly affect their excitability. In the present work, we have investigated the regulation of the afterhyperpolarizing current (IAHP) by protein kinase C (PKC). Electrophysiological responses and protein translocation were investigated in AH neurons of freshly dissected preparations of myenteric ganglia from the guinea‐pig ileum. The activator of conventional and novel PKCs, phorbol dibutyrate, but not the activator of novel PKCs, ingenol, blocked the IAHP. Phorbol dibutyrate had no effect on the hyperpolarization‐activated current (Ih) or on the A current (IA). Stimulation of synaptic inputs to the neurons also reduced the IAHP, and had no effect on Ih or IA. Phorbol dibutyrate also reduced a background outward current that was present after the IAHP current had been blocked by clotrimazole. Both phorbol dibutyrate and ingenol caused translocation of the novel PKC, PKCε, in these neurons. Only phorbol dibutyrate caused translocation of PKCγ, a conventional PKC. The studies thus indicate that the activation of PKC by phorbol esters and by nerve stimulation affects AH neurons in a similar way, and that PKC activation targets both the IAHP and another background K+ current. The IAHP is targeted by a conventional PKC, suggested to be PKCγ, as this is the only conventional PKC that is prominent in AH neurons.
Correlation between multiple climbing fibre regression and parallel fibre response development in the postnatal mouse cerebellum
Authors: Scelfo Bibiana , Strata Piergiorgio 
Published: March 2005

AbstractAt the neuromuscular junction elimination of supernumerary synaptic connections during development is owing to a competitive process between single neuronal populations, whereas in the central nervous system the interaction of different types of input could affect the process. In the cerebellum, the regression from multiple‐ to mono‐innervation of the Purkinje cells by climbing fibres is virtually completed during the first two weeks of postnatal development. While it is clear that parallel fibres are important in the control of the regression, there are conflicting results in relation to whether an early phase of regression is independent of parallel fibre effects. We studied the precise timing of climbing fibre synapse development and decline and the relationship with the functional maturation of parallel fibres. Until postnatal day (P) 6 or 7, the synaptic currents generated by different climbing fibres become progressively more uniform in amplitude. However, between P7 and 14, the amplitudes of the currents increasingly diverge until only one fibre remains connected. These data are taken as evidence that, in multiply innervated Purkinje cells, competition between different climbing fibres appears at P7 and continues during the second postnatal week. Morphological and electrophysiological data demonstrate that parallel fibres synapses appear at P7 and their development is significantly correlated with the time course of the climbing fibre regression. These results provide no evidence for climbing fibre regression independent of parallel fibres before P7 and also suggest a dominant role of the parallel fibre input in the later phase.
Homogeneous distribution of large‐conductance calcium‐dependent potassium channels on soma and apical dendrite of rat neocortical layer 5 pyramidal neurons
Authors: Benhassine Narimane , Berger Thomas 
Published: March 2005

AbstractVoltage‐gated conductances on dendrites of layer 5 pyramidal neurons participate in synaptic integration and output generation. We investigated the properties and the distribution of large‐conductance calcium‐activated potassium channels (BK channels) in this cell type using excised patches in acute slice preparations of rat somatosensory cortex. BK channels were characterized by their large conductance and sensitivity to the specific blockers paxilline and iberiotoxin. BK channels showed a pronounced calcium‐dependence with a maximal opening probability of 0.69 at 10 µmand 0.42 at 3 µmfree calcium. Their opening probability and transition time constants between open and closed states are voltage‐dependent. At depolarized potentials, BK channel gating is described by two open and one closed states. Depolarization increases the opening probability due to a prolongation of the open time constant and a shortening of the closed time constant. Calcium‐dependence and biophysical properties of somatic and dendritic BK channels were identical. The presence of BK channels on the apical dendrite of layer 5 pyramidal neurons was shown by immunofluorescence. Patch‐clamp recordings revealed a homogeneous density of BK channels on the soma and along the apical dendrite up to 850 µm with a mean density of 1.9 channels per µm2. BK channels are expressed either isolated or in clusters containing up to four channels. This study shows the presence of BK channels on dendrites. Their activation might modulate the shape of sodium and calcium action potentials, their propagation along the dendrite, and thereby the electrotonic distance between the somatic and dendritic action potential initiation zones.
Dynamics of learning‐induced spine redistribution along dendrites of pyramidal neurons in rats
Authors: Knafo Shira , Libersat Frederic , Barkai Edi 
Published: March 2005

AbstractWe have previously shown that olfactory‐discrimination (OD) learning is accompanied by enhanced spine density along proximal apical dendrites of layer II pyramidal neurons in the piriform (olfactory) cortex. Here we studied the temporal dynamics of learning‐induced modifications in dendritic spine density throughout the dendritic trees of these neurons. We observed a transient increase in proximal apical spine density after OD learning, suggesting a strengthening of intrinsic excitatory inputs interconnecting neurons within the olfactory cortex. By contrast, the afferent pathway receiving direct input from the olfactory bulb shows spine pruning, suggesting that the connectivity is weakened. The changes in spine density can be attributed to a net change in number of spines, as the morphometric parameters of the dendrites are unaffected by learning. We suggest that spine density changes may represent a mechanism of selective synaptic reorganization required for olfactory learning consolidation.
The neural correlate of very‐long‐term picture priming
Authors: Meister Ingo G. , Weidemann Jürgen , Foltys Henrik , Brand Henning , Willmes Klaus , Krings Timo , Thron Armin , Töpper Rudolf , Boroojerdi Babak 
Published: March 2005

AbstractRepetition priming denotes a behavioural change caused by prior exposure to a stimulus. The effect is known to last for weeks. This study addresses the underlying neural mechanisms for very‐long‐term picture priming by using event‐related functional magnetic resonance imaging complemented by a behavioural paradigm. Previous functional imaging studies with shorter retention intervals have shown that priming is associated with changes in the activity of both the occipital and posterior temporal cortex. In this study we compared retention intervals of 1 day and 6 weeks after initial exposure to a picture stimulus. Priming‐related decreases in cortical activity in posterior extrastriate and dorsal left inferior frontal areas were found only for the shorter retention interval. In contrast, fMRI activation in the inferior posterior temporal and anterior left inferior frontal cortex was reduced following priming for both retention intervals. In the behavioural paradigm, the priming effect was stable over time. We conclude that the left inferior frontal and inferior posterior temporal cortex play a key role in the very‐long‐term priming effect.
Stopping-Time Resampling for Sequential Monte Carlo Methods
Authors: Chen Yuguo , Xie Junyi , Liu Jun S. 
Published: March 2005

SummaryMotivated by the statistical inference problem in population genetics, we present a new sequential importance sampling with resampling strategy. The idea of resampling is key to the recent surge of popularity of sequential Monte Carlo methods in the statistics and engin-eering communities, but existing resampling techniques do not work well for coalescent-based inference problems in population genetics. We develop a new method called ‘stopping-time resampling’, which allows us to compare partially simulated samples at different stages to terminate unpromising partial samples and to multiply promising samples early on. To illustrate the idea, we first apply the new method to approximate the solution of a Dirichlet problem and the likelihood function of a non-Markovian process. Then we focus on its application in population genetics. All our examples show that the new resampling method can significantly improve the computational efficiency of existing sequential importance sampling methods.
Model-Free Variable Selection
Authors: Li Lexin , Dennis Cook R. , Nachtsheim Christopher J. 
Published: March 2005

SummaryThe importance of variable selection in regression has grown in recent years as computing power has encouraged the modelling of data sets of ever-increasing size. Data mining applications in finance, marketing and bioinformatics are obvious examples. A limitation of nearly all existing variable selection methods is the need to specify the correct model before selection. When the number of predictors is large, model formulation and validation can be difficult or even infeasible. On the basis of the theory of sufficient dimension reduction, we propose a new class of model-free variable selection approaches. The methods proposed assume no model of any form, require no nonparametric smoothing and allow for general predictor effects. The efficacy of the methods proposed is demonstrated via simulation, and an empirical example is given.
Astrocyte activation by fibroblast growth factor‐1 and motor neuron apoptosis: implications for amyotrophic lateral sclerosis
Authors: Cassina Patricia , Pehar Mariana , Vargas Marcelo R. , Castellanos Raquel , Barbeito Ana G. , Estévez Alvaro G. , Thompson John A. , Beckman Joseph S. , Barbeito Luis 
Published: March 2005

AbstractFibroblast growth factor‐1 (FGF1 or acidic FGF) is highly expressed in motor neurons. FGF‐1 is released from cells by oxidative stress, which might occur from SOD‐1 aberrant function in amyotrophic lateral sclerosis (ALS). Although FGF‐1 is known to be neuroprotective after spinal cord injury or axotomy, we found that FGF‐1 could activate spinal cord astrocytes in a manner that decreased motor neuron survival in co‐cultures. FGF‐1 induced accumulation of the FGF receptor 1 (FGFR1) in astrocyte nuclei and potently stimulated nerve growth factor (NGF) expression and secretion. The FGFR1 tyrosine kinase inhibitor PD166866 prevented these effects. Previously, we have shown that NGF secretion by reactive astrocytes induces motor neuron apoptosis through a p75NTR‐dependent mechanism. Embryonic motor neurons co‐cultured on the top of astrocytes exhibiting activated FGFR1 underwent apoptosis, which was prevented by PD166866 or by adding either anti‐NGF or anti‐p75NTR neutralizing antibodies. In the degenerating spinal cord of mice carrying the ALS mutation G93A of Cu, Zn superoxide dismutase, FGF‐1 was no longer localized only in the cytosol of motor neurons, while FGFR1 accumulated in the nuclei of reactive astrocytes. These results suggest that FGF‐1 released by oxidative stress from motor neurons might have a role in activating astrocytes, which could in turn initiate motor neuron apoptosis in ALS through a p75NTR‐dependent mechanism.
Increased phosphorylation and redistribution of NMDA receptors between synaptic lipid rafts and post‐synaptic densities following transient global ischemia in the rat brain
Authors: Besshoh Shintaro , Bawa Damanpreet , Teves Lucy , Wallace M. Christopher , Gurd James W. 
Published: March 2005

AbstractIschemia results in increased phosphorylation of NMDA receptors. To investigate the possible role of lipid rafts in this increase, lipid rafts and post‐synaptic densities (PSDs) were isolated by the extraction of rat brain synaptosomes with Triton X‐100 followed by sucrose density gradient centrifugation. Lipid rafts accounted for the majority of PSD‐95, whereas SAP102 was predominantly located in PSDs. Between 50 and 60% of NMDA receptors were associated with lipid rafts. Greater than 85–90% of Src and Fyn were present in lipid rafts, whereas Pyk2 was mainly associated with PSDs. Lipid rafts and PSDs were isolated from animals subjected to 15 min of global ischemia followed by 6 h of recovery. Ischemia did not affect the yield, density, flotillin‐1 or cholesterol content of lipid rafts. Following ischemia, the phosphorylation of NR1 by protein kinase C and tyrosine phosphorylation of NR2A and NR2B was increased in both lipid rafts and PSDs, with a greater increase in tyrosine phosphorylation occurring in the raft fraction. Following ischemia, NR1, NR2A and NR2B levels were elevated in PSDs and reduced in lipid rafts. The findings are consistent with a model involving close interaction between lipid rafts and PSDs and a role for lipid rafts in ischemia‐induced signaling pathways.
Activation of c‐Jun‐N‐terminal kinase is critical in mediating lipopolysaccharide‐induced changes in the rat hippocampus
Authors: Barry Claire E. , Nolan Yvonne , Clarke Rachael M. , Lynch Aileen , Lynch Marina A. 
Published: March 2005

AbstractLipopolysaccharide (LPS) exerts a myriad of effects in rat hippocampus; it increases the concentration of the proinflammatory cytokine, interleukin‐1β (IL‐1β), and signalling via the IL‐1 type I receptor (IL‐1RI) resulting in phosphorylation of the stress‐activated protein kinase, c‐jun‐N‐terminal kinase (JNK) and impairment in long‐term potentiation (LTP). This study was designed to establish whether activation of JNK is a pivotal event in mediating the effects of LPS in hippocampus and therefore LPS‐treated rats were injected intracerebroventricularly with saline, the JNK inhibitor D‐JNKI1, or with the anti‐inflammatory cytokine IL‐4, which antagonizes the effects of IL‐1β upstream of JNK activation. We report that IL‐4 blocked the LPS‐induced increase in IL‐1RI expression and associated increases in phosphorylation of JNK and c‐jun, whereas D‐JNKI1 inhibited the LPS‐induced phosphorylation of c‐jun. Both IL‐4 and D‐JNKI1 inhibited the increase in caspase‐3 staining which was associated with LPS treatment, and both abrogated the LPS‐induced inhibition of LTP in perforant path‐granule cell synapses. The data presented are consistent with the proposal that JNK activation, probably as a result of increased IL‐1RI activation, is a critical step in mediating the detrimental effects of LPS in hippocampus.
Protection by exogenous pyruvate through a mechanism related to monocarboxylate transporters against cell death induced by hydrogen peroxide in cultured rat cortical neurons
Authors: Nakamichi Noritaka , Kambe Yuki , Oikawa Hirotaka , Ogura Masato , Takano Katsura , Tamaki Keisuke , Inoue Maki , Hinoi Eiichi , Yoneda Yukio 
Published: March 2005

AbstractIn cortical neurons cultured for 3 or 9 days in vitro (DIV), exposure to hydrogen peroxide (H2O2) led to a marked decrease in cell viability in a concentration‐dependent manner at a concentration range of 10 µm to 1 mm irrespective of the duration between 6 and 24 h. However, H2O2 was more potent in decreasing cellular viability in cortical neurons cultured for 9 DIV than in those for 3 DIV. Pyruvate was effective in preventing the neuronal cell death at 1 mm even when added 1–3 h after the addition of H2O2. Semi‐quantitative RT–PCR and western blotting analyses revealed significantly higher expression of both mRNA and protein for a particular monocarboxylate transporter (MCT) in neurons cultured for 9 DIV than in those for 3 DIV. A specific inhibitor of MCT significantly attenuated the neuroprotection by pyruvate in neurons cultured for 9 DIV, without markedly affecting that in neurons cultured for 3 DIV. These results suggest that vulnerability to H2O2 may at least in part involve expression of particular MCT isoforms responsible for the bi‐directional transport of pyruvate across cell surfaces in cultured rat cortical neurons.
Nuclear Ca2+ and CaM kinase IV specify hormonal‐ and Notch‐responsiveness
Authors: Mckenzie Grahame J. , Stevenson Patrick , Ward George , Papadia Sofia , Bading Hilmar , Chawla Sangeeta , Privalsky Martin , Hardingham Giles E. 
Published: March 2005

AbstractMany neuronal processes require gene activation by synaptically evoked Ca2+ transients. Ca2+‐dependent signal pathways activate some transcription factors outright, but here we report that such signals also potentiate the activation of nuclear receptors by their cognate hormone, and of CBF1 by Notch, transcription factors hitherto not thought to be Ca2+‐responsive. This potentiation is occluded by histone deacetylase inhibition, indicating a mechanism involving inactivation of co‐repressors associated with these transcription factors. Synaptic activity, acting via the nuclear Ca2+‐dependent activation of CaM kinase IV, triggers the disruption of subnuclear domains containing class II histone deacetylases (HDACs) and silencing mediator of retinoic acid and thyroid hormone receptors (SMRT), a broad‐specificity co‐repressor which represses nuclear hormone receptors and CBF1. The sequential loss of class II HDACs and SMRT from the subnuclear domains, followed by nuclear export, is associated with disruption of SMRT interaction with its target transcription factors and sensitization of these factors to their activating signal. Counterbalancing these changes, protein phosphatase 1 promotes nuclear localization of SMRT and inactivation of nuclear receptors and CBF1. Thus, the synaptically controlled kinase‐phosphatase balance of the neuron determines the efficacy of SMRT‐mediated repression and the signal‐responsiveness of a variety of transcription factors.
The role of tyrosine kinase‐mediated pathways in diabetes‐induced alterations in responsiveness of rat carotid artery
Authors: Yousif M. H. M. , Benter I. F. , Akhtar S. 
Published: March 2005

Summary 1 G‐protein‐coupled receptor signalling, including transactivation of receptor tyrosine kinases (RTKs), has been implicated in vascular pathology. However, the role of specific RTKs in the development of diabetes‐induced cardiovascular complications is not known. 2 We investigated the ability of a chronic administration of genistein, a broad‐spectrum inhibitor of tyrosine kinases (TKs), AG1478, a specific inhibitor of epidermal growth factor receptor (EGFR) TK activity, and AG825, a specific inhibitor of Erb2, to modulate the altered vasoreactivity of isolated carotid artery ring segments to common vasoconstrictors and vasodilators in streptozotocin (STZ)‐induced diabetes. 3 In diabetic carotid artery, the vasoconstrictor responses induced by noradrenaline (NE), endothelin‐1 (ET‐1), and angiotensin II (Ang II), were significantly increased whereas vasodilator responses to carbachol and histamine were significantly reduced. Inhibition of TKs, EGFR or Erb2 pathway did not affect the body weight or agonist‐induced vasoconstrictor and vasodilator responses in the non‐diabetic control animals. However, inhibition of TKs by genistein, EGFR TK by AG1478 or Erb2 by AG825 treatment produced a significant normalization of the altered agonist‐induced vasoconstrictor responses without affecting blood glucose levels. Treatment with diadzein, an inactive analogue of genistein, did not affect the vasoconstrictor and vasodilator responses in the diabetic animals. 4 Treatment with genistein, AG1478 or AG825 resulted in a significant improvement in diabetes‐induced impairment in endothelium‐dependent relaxation to carbachol and histamine. 5 These data suggest that activation of TK‐mediated pathways, including EGFR TK signalling and Erb2 pathway, are involved in the development of diabetic vascular dysfunction in the carotid artery.