bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lateral cerebellum: functional localization within crus I and correspondence to cortical zones
Authors: Edge Antonia L. , Marple‐Horvat Dilwyn E. , Apps Richard 
Published: September 2003

AbstractThe present study investigates the functional connections of different parts of the medial‐most folium of crus I in the cat cerebellar hemisphere. Three areas were identified physiologically by recording on the cerebellar surface climbing fibre (CF) field potentials evoked by electrical stimulation of different body sites. From medial to lateral in relation to the long axis of the folium, area 1 receives convergent input from all body sites tested (optic chiasm, ipsilateral periorbital region, ipsilateral and contralateral forelimbs), area 2 receives input mainly from the ipsilateral periorbital region, while area 3 receives input mainly from the optic chiasm. These physiological differences were used to guide injections of bi‐directional tracer material into individual cortical areas. The inferior olive and cerebellar nuclei were then mapped, revealing a precise topography within the olivo‐cerebellar and cortico‐nuclear projections for each area. On the basis of their anatomical and physiological characteristics areas 1, 2 and 3 correspond to zones C2, C3 and D1, respectively. CF inputs arise from the rostral medial accessory olive (C2), the interface between the rostral dorsal accessory olive and ventral lamella of the principal olive (vlPO, C3), and from vlPO (D1). The corresponding cortico‐nuclear projections are nucleus interpositus posterior (C2), the transitional region between the dentate nucleus and nucleus interpositus anterior (C3), and the dentate nucleus (D1). Overall, the results provide a comprehensive description of the functional localization of different zones within crus I (folium 1), and suggest that a potent source of CF input to the C2 and D1 zones within this region of cortex arises from visual pathways.
Endogenous 5‐HT, released by MDMA through serotonin transporter‐ and secretory vesicle‐dependent mechanisms, reduces hippocampal excitatory synaptic transmission by preferential activation of 5‐HT1B receptors located on CA1 pyramidal neurons
Authors: Mlinar Boris , Corradetti Renato 
Published: September 2003

AbstractA multitude of different serotonin (5‐HT) receptor types are expressed in the hippocampus, but the identity of receptors actually mediating the physiological response to endogenous 5‐HT has not been determined. We combined pharmacologically induced release of 5‐HT with patch‐clamp recordings on disinhibited rat CA1 minislices to determine effects of endogenous 5‐HT on the excitability of pyramidal neurons and synaptic transmission among them. We found that application of 5‐HT releasers, 3,4‐methylenedioxy‐methamphetamine (MDMA) or p‐methylthioamphetamine, at concentrations ranging from 2 to 50 µm, reduced the excitatory synaptic transmission between CA1 pyramidal neurons without altering their basal electrical properties. This effect of MDMA was blocked by the selective 5‐HT1B antagonist GR 55562, was dependent on endogenous 5‐HT content and was mediated by presynaptically located, pertussis‐toxin sensitive mechanisms. We found no other MDMA effects in our preparation, which indicates that the release of endogenous 5‐HT preferentially stimulates 5‐HT1B receptors on CA1 pyramidal neurons. Therefore, 5‐HT1B receptor activation may represent a predominant component of the physiological response to endogenous 5‐HT in the CA1. The high sensitivity of the 5‐HT1B receptor‐mediated reduction of polysynaptic excitatory responses to the extracellular 5‐HT level enabled us to study mechanisms of the 5‐HT releasing action of MDMA. Block of the serotonin transporter (SERT) with citalopram slowed the time course and reduced overall 5‐HT release by MDMA. Depletion of vesicular 5‐HT, by inhibition of vesicular monoamine transporter type 2 with tetrabenazine prevented the release. Thus although the SERT reversal contributes, a direct vesicle‐depleting action is essential for MDMA release of 5‐HT.
Repeated methylphenidate treatment in adolescent rats alters gene regulation in the striatum
Authors: Brandon Cindy L. , Steiner Heinz 
Published: September 2003

AbstractMethylphenidate is a psychostimulant which inhibits the dopamine transporter and produces dopamine overflow in the striatum, similar to the effects of cocaine. Excessive dopamine action is often associated with changes in gene expression in dopamine‐receptive neurons. Little is known about methylphenidate's effects on gene regulation. We investigated whether a methylphenidate treatment regimen known to produce behavioural changes would alter gene expression in the striatum. Using in situ hybridization histochemistry, we assessed the effects of acute and repeated methylphenidate treatment on the expression of immediate–early genes (c‐fos, zif 268) and neuropeptides (dynorphin, substance P, enkephalin) in adolescent rats. Acute methylphenidate treatment (0–10 mg/kg, i.p.) produced a dose‐dependent increase in the expression of c‐fos and zif 268. These effects were most pronounced in the dorsal striatum at middle to caudal striatal levels, and were found for doses as low as 2 mg/kg. Repeated treatment with methylphenidate (10 mg/kg/day, 7 days) increased the expression of dynorphin, which was highly correlated with the acute immediate–early gene response across different striatal regions. Moreover, after repeated methylphenidate treatment, cocaine‐induced expression of c‐fos and zif 268, as well as of substance P, was significantly attenuated throughout the striatum. These effects of repeated methylphenidate treatment mirror those produced by repeated treatment with cocaine or other psychostimulants and are considered to reflect drug‐induced neuroadaptations. Thus, our findings demonstrate that acute and repeated methylphenidate treatment can produce molecular alterations similar to other psychostimulants.
Effects of levodopa on endocannabinoid levels in rat basal ganglia: implications for the treatment of levodopa‐induced dyskinesias
Authors: Ferrer Belen , Asbrock Nick , Kathuria Satish , Piomelli Daniele , Giuffrida Andrea 
Published: September 2003

AbstractThe majority of Parkinson's disease patients undergoing levodopa therapy develop disabling motor complications (dyskinesias) within 10 years of treatment. Stimulation of cannabinoid receptors, the pharmacological target of Δ9‐tetrahydrocannabinol, is emerging as a promising therapy to alleviate levodopa‐associated dyskinesias. However, the mechanisms underlying this beneficial action remain elusive, as do the effects exerted by levodopa therapy on the endocannabinoid system. Although levodopa is known to cause changes in CB1 receptor expression in animal models of Parkinson's disease, we have no information on whether this drug alters the brain concentrations of the endocannabinoids anandamide and 2‐arachidonylglycerol. To address this question, we used an isotope dilution assay to measure endocannabinoid levels in the caudate–putamen, globus pallidus and substantia nigra of intact and unilaterally 6‐OHDA‐lesioned rats undergoing acute or chronic treatment with levodopa (50 mg/kg). In intact animals, systemic administration of levodopa increased anandamide concentrations throughout the basal ganglia via activation of dopamine D1/D2 receptors. In 6‐OHDA‐lesioned rats, anandamide levels were significantly reduced in the caudate–putamen ipsilateral to the lesion; however, neither acute nor chronic levodopa treatment affected endocannabinoid levels in these animals. In lesioned rats, chronic levodopa produced increasingly severe oro‐lingual involuntary movements which were attenuated by the cannabinoid agonist R(+)‐WIN55,212‐2 (1 mg/kg). This effect was reversed by the CB1 receptor antagonist rimonabant (SR141716A). These results indicate that a deficiency in endocannabinoid transmission may contribute to levodopa‐induced dyskinesias and that these complications may be alleviated by activation of CB1 receptors.
Long‐term behavioural, molecular and morphological effects of neonatal NMDA receptor antagonism
Authors: Wiseman Harris Laura , Sharp Trevor , Gartlon Jane , Jones Declan N. C. , Harrison Paul J. 
Published: September 2003

AbstractBrief N‐methyl‐d‐aspartate (NMDA) receptor blockade in neonatal rats has been reported to increase neuronal apoptosis. We replicated this finding using MK‐801 (0.5 mg/kg) administered twice on postnatal day 7, and then studied the long‐term consequences. In adulthood, treated rats showed reduced volume and neuronal number within the hippocampus, and altered hippocampal NMDA receptor (NR1 subunit) expression. Synaptophysin mRNA was decreased in the thalamus (laterodorsal nucleus). Adult MK‐801‐treated females had prepulse inhibition deficits and increased locomotor activity. The data show that a transient and limited glutamatergic intervention during development can have chronic behavioural, structural and molecular effects. The effects are reminiscent of alterations reported in schizophrenia and, as such, are consistent with hypotheses advocating a role for NMDA receptor hypofunction, and aberrant apoptosis, in the neurodevelopmental pathogenesis of the disorder.
fMRI Activation in Continuous and Spike‐triggered EEG–fMRI Studies of Epileptic Spikes
Authors: Al‐Asmi Abdulla , Bénar Christian‐G. , Gross Don W. , Khani Yayha Agha , Andermann Frederick , Pike Bruce , Dubeau François , Gotman Jean 
Published: September 2003

Summary:  Purpose: To evaluate functional magnetic resonance imaging (fMRI) with simultaneous EEG for finding metabolic sources of epileptic spikes. To find the localizing value of activated regions and factors influencing fMRI responses. Methods: Patients with focal epilepsy and frequent spikes were subjected to spike‐triggered or continuous fMRI with simultaneous EEG. Results were analyzed in terms of fMRI activation, concordance with the location of EEG spiking and anatomic MRI abnormalities, and other EEG and clinical variables. In four patients, results also were compared with those of intracerebral EEG. Results: Forty‐eight studies were performed on 38 patients. Seventeen studies were not analyzed, primarily because no spikes occurred during scanning. Activation was obtained in 39% of 31 studies, with an activation volume of 2.55 ± 4.84 cc. Activated regions were concordant with EEG localization in almost all studies and confirmed by intracerebral EEG in four patients. Forty percent of patients without an MRI lesion showed activation; 37.5% of patients with a lesion had an activation; the activation was near or inside the lesion. Bursts of spikes were more likely to generate an fMRI response than were isolated spikes (76 vs. 11%; p < 0.05). Conclusions: Combining EEG and fMRI in focal epilepsy yields regions of activation that are presumably the source of spiking activity. These regions are highly linked with epileptic foci and epileptogenic lesions in a significant number of patients. Activation also is found in patients with no visible MRI lesion. Intracerebral recordings largely confirm that these activation regions represent epileptogenic areas. It is still unclear why many patients show no activation.
The Clinical Spectrum of Epilepsy in Children and Adults with Hypothalamic Hamartoma
Authors: Mullatti Nandini , Selway Richard , Nashef Lina , Elwes Robert , Honavar Mrinalini , Chandler Christopher , Morris Robin , Jarosz Josef , Buchanan Charles , Polkey Charles 
Published: September 2003

Summary:  Purpose: Hamartomas of the hypothalamus (HH) cause an uncommon and unusual epilepsy syndrome. The condition is recognized to affect children, but the presentation in adults is not well understood. We present 19 children and adult patients with HH, including three patients whose epilepsy began in adult life. The patterns of clinical presentation, evolution of the epilepsy from childhood to adult life, and electroclinical diagnostic features are presented. Methods: Nineteen patients, both children and adults with HH and epilepsy, were evaluated clinically, with EEG, video‐EEG, and magnetic resonance imaging (MRI) scanning. Seven patients underwent surgical resection of the hamartoma. Stereotactic thermocoagulation of the hamartoma was performed in two patients. Results: Gelastic seizures occurred at onset of epilepsy in 15 of 16 early‐onset cases. Subsequently, multiple seizures types occurred, which then evolved to mainly partial epilepsy with tonic or complex partial seizures (five of eight adults), or became entrenched symptomatic generalized epilepsy with atypical absences, drop attacks, and secondarily generalized seizures, and cognitive impairment (three of eight adults). In the adult‐onset patients, gelastic seizures were not prominent, the epilepsy was milder, and they functioned normally. Stereotactic thermocoagulation of the hamartoma resulted in improvement in seizure control in two patients. Conclusions: Gelastic seizures are not a prominent feature of epilepsy in adult patients with HH. The epilepsy associated with HH, although severe at onset, can evolve into a milder syndrome in later life. For less severely affected patients, minimally invasive alternatives to the traditionally difficult open surgical treatment should be considered.
Organizational Culture and Knowledge Management
Authors: Lim Thou Tin 
Published: September 2003

As organizations in Singpore respond to the pressures of globalization, the adoption of knowledge management practices becomes more prevalent. In a hurry to implement this new business paradigm, organizations may have overlooked the influence of the cultural context which is commonly considered one of the pillars of knowledge management in a western-oriented organization. This paper examines what was overlooked by Singapore organizations while moving towards knowledge management. Specifically, it studies the impact of organizational culture on knowledge management processes. A review of literature shows that there is a relationship between cultural factors and knowledge management processes. This relationship is reflected in a research model that helps to answer research questions and to formulate hypotheses for testing. The result indicates that knowledge management should consider not just the technological aspects of implementation but also the cultural, leadership and contextual aspects of an organization.
Dynamic Stereochemistry of Alkyltris(9-triptycyl)stannanes
Authors: Yamamoto Gaku , Kaneko Megumi , Ohkuma Miki , Minoura Mao 
Published: September 2003

Abstract
1H dynamic NMR study of benzyltris(9-triptycyl)stannane (4) using two probes, the benzylic methylene and the aromatic peri-proton signals, revealed that the enantiomerization of the chiral conformers took place with ΔG‡ of 64.2 kJ mol−1 at 300 K.
Relationship between Molecular Skeleton and Stimulated-emission Threshold in Dilute Thin Films of Linear-chain-structured Fluorescent Dyes
Authors: Sakai Ken-ichi , Tsuzuki Takeo , Motoyoshiya Jiro , Inoue Masamitsu , Itoh Yoshihiro , Ichikawa Musubu , Fujimoto Tetsuya , Yamamoto Iwao , Koyama Toshiki , Taniguchi Yoshio 
Published: September 2003

Abstract
We carried out photopumping measurements for the dilute thin films of linear-chain-structured laser dyes where π-units such as benzene, ethylene, and oxazole are linearly linked via σ-bonds. Among them, 4-4′-bis[4-(di-p-tolylamino)styryl]biphenyl recorded the lowest stimulated-emission threshold of 2 μJ/cm2. It was revealed that the threshold was related to whether the number of constituent π-units was even or odd.
Structural modification of expandable polystyrene. I. Copolymerization with α‐methylstyrene
Authors: Taşkiran Isa , Sunal Gürkan , Erbay Erol , Uyanik Nurseli 
Published: September 2003

AbstractConventional expandable polystyrene (EPS) was modified by the preparation of copolymers containing 1.0, 2.5, and 5.0% α‐methylstyrene. Increasing the glass‐transition temperature of EPS was the aim of this work. Copolymeric expandable polystyrene (CEPS) samples were characterized with various techniques. 1H‐NMR spectroscopy was used for the determination of the composition, and gel permeation chromatography was used for the determination of the molecular weights and molecular weight distributions. Differential scanning calorimetry showed that the glass‐transition temperatures of the CEPS samples increased with increasing α‐methylstyrene contents. The prevention of the collapse of the EPS cells was observed in scanning electron microscopy images of the inner portions and outer surfaces of the CEPS samples. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 609–614, 2003
A study of dynamic vulcanization for polyamide‐12 and chlorobutyl rubber
Authors: Van Dyke J. D. (Jack) , Gnatowski Marek , Koutsandreas Andy , Burczyk Andrew 
Published: September 2003

AbstractPolyamide‐12 and chlorobutyl rubber were blended by dynamic vulcanization in a high shear environment using curing systems based on sulfur, dithiocarbamate/ZnO, and 4,4‐methylenebiscyclohexylamine/MgO. As expected, all blends with curing agents show increased tensile strength and elongation at break in comparison to blends without curing agents. Maximum mechanical properties are obtained at relatively low levels of curing agent in all systems. Hexane extraction of the mixtures and measurement of percentage of insolubles along with the swelling index of the rubber phase confirm that a high level of cure is achieved at low levels of curing agent. Although the curatives are designed for the rubber phase, differential scanning calorimetry results indicate that both phases are affected during the dynamic vulcanization process, with polyamide‐12 showing a reduced melting temperature that is indicative of molecular weight reduction, structure changes, or reaction with the rubber phase. Scanning electron microscopy results indicate that phase size is reduced with increased blending time and level of curing agent. Rheological studies indicate that blends containing curing agents exhibit non‐Newtonian behavior to a greater extent than polyamide or nonvulcanized polyamide/chlorobutyl rubber blends. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 871–880, 2003
In vivo analysis of the apoptosis‐inducing effect of anti–endothelial cell antibodies in systemic sclerosis by the chorionallantoic membrane assay
Authors: Worda Miriam , Sgonc Roswitha , Dietrich Hermann , Niederegger Harald , Sundick Roy S. , Gershwin M. Eric , Wick Georg 
Published: September 2003

AbstractObjectiveSystemic sclerosis (SSc) is a connective tissue disease of unknown etiology characterized by mononuclear cell infiltration and fibrosis. Vascular injury occurs early in the course of disease, and previous in vitro studies suggest a primary role for anti–endothelial cell antibodies (AECAs) in mediating endothelial cell apoptosis. The aim of the present study was to analyze the apoptosis‐inducing effect of AECAs in vivo.MethodsThe optimum animal model for transfer experiments was the University of California at Davis line 200 (UCD‐200) chickens that spontaneously develop a hereditary disease with features closely resembling those of scleroderma in humans. AECA‐positive serum samples from UCD‐200 chickens were used for intravenous injection into normal CC chicken embryos on embryonic day (ED) 13 as well as for application onto chorionallantoic membranes (CAMs) of healthy control lines on ED 10. CAMs of ED 16 embryos and combs of 1‐week‐old CC chickens that had received the injected serum samples were analyzed for apoptotic endothelial cells by TUNEL.ResultsStaining of frozen CAM sections by immunofluorescence showed evidence of in vivo binding of AECAs to the microvascular endothelium. In most groups, transfer of AECA‐positive sera resulted in a significant increase in endothelial cell apoptosis as compared with controls.ConclusionThis study is the first to demonstrate the in vivo apoptosis‐inducing effects of AECAs. The findings support our hypothesis of a primary pathogenetic role of AECAs in SSc.
Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor α–induced angiogenesis in rheumatoid arthritis
Authors: DeBusk Laura M. , Chen Ying , Nishishita Toshihide , Chen Jin , Thomas James W. , Lin Pengnain Charles 
Published: September 2003

AbstractObjectiveRheumatoid arthritis (RA) is an inflammatory disease and an angiogenic disease. However, the molecular mechanisms promoting angiogenesis in RA are not clearly identified. Our objective was to study the role of an endothelium‐specific receptor tyrosine kinase, Tie2, in angiogenesis of inflammatory arthritis.MethodsExpression of Tie2 and its ligand, angiopoietin 1 (Ang1), in human synovium was examined by immunohistochemistry and Western blot. A novel synovium vascular window model was established to study the role of Tie2 in angiogenesis in vivo. Primary cultured endothelial cells and synoviocytes were used to study tumor necrosis factor α (TNFα)–induced Tie2 and Ang1 expression.ResultsTie2 was implicated in pathologic angiogenesis. We observed that Tie2 and Ang1 were elevated in human RA synovium. Using a novel collagen‐induced arthritis synovial window model, we demonstrated that Tie2 signaling regulated arthritis angiogenesis in vivo. We also showed that Tie2 mediated TNFα‐induced angiogenesis in a mouse cornea assay. In addition, we observed that TNFα can regulate Tie2 activation in multiple ways that may involve interactions between endothelial cells and synoviocytes. TNFα up‐regulates Tie2 in endothelial cells through nuclear factor κB, and it up‐regulates Ang1 in synoviocytes. These findings suggest paracrine regulation of angiogenesis between endothelial cells and synoviocytes.ConclusionThis study demonstrates that Tie2 regulates angiogenesis in inflammatory synovium. Tie2 signaling is an important angiogenic mediator that links the proinflammatory cytokine TNFα to pathologic angiogenesis.
Suppression of arthritic bone destruction by adenovirus‐mediated dominant‐negative Ras gene transfer to synoviocytes and osteoclasts
Authors: Yamamoto Aiichiro , Fukuda Akira , Seto Hiroaki , Miyazaki Tsuyoshi , Kadono Yuho , Sawada Yasuhiro , Nakamura Ichiro , Katagiri Hideki , Asano Tomoichiro , Tanaka Yoshiya , Oda Hiromi , Nakamura Kozo , Tanaka Sakae 
Published: September 2003

AbstractObjectiveTo determine the role of Ras‐mediated signaling pathways in synovial cell activation and bone destruction in arthritic joints.MethodsThe E11 rheumatoid synovial cell line and primary synovial fibroblast‐like cells (SFCs) from patients with rheumatoid arthritis (RA) were gene‐transferred by replication‐deficient adenovirus vector carrying the dominant‐negative mutant of the ras gene (AxRasDN). The effects of RasDN overexpression on cellular proliferation, interleukin‐1 (IL‐1)–induced activation of mitogen‐activated protein kinases (extracellular signal–regulated kinase [ERK], p38, c‐Jun N‐terminal kinase [JNK]), and IL‐6 production by synovial cells were analyzed. The in vivo effects of Ras inhibition on synovial cell activation and arthritic bone destruction were analyzed by injection of AxRasDN into ankle joints of rats with adjuvant arthritis.ResultsAxRasDN markedly reduced the proliferation of RA SFCs. IL‐1, a proinflammatory cytokine involved in RA pathology, induced activation of ERK, p38, and JNK in the cells. Adenovirus vector–mediated RasDN overexpression suppressed ERK activation, but not p38 or JNK activation, in SFCs. IL‐6 is also an important proinflammatory cytokine, and RasDN inhibited IL‐1–induced production of IL‐6 by RA SFCs at both the transcriptional and protein levels. Injection of AxRasDN into ankle joints of rats with adjuvant arthritis ameliorated inflammation and suppressed bone destruction in the affected joints.ConclusionRas‐mediated signaling pathways are involved in the activation of RA SFCs and the destruction of bone in arthritic joints, suggesting that inhibition of Ras signaling can be a novel approach for RA treatment that targets both synovial cell activation and bone destruction in the RA joint.