bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissociation of ionized benzophenones investigated by the kinetic method: effective temperature, steric effects and gas‐phase CO+• affinities of phenyl radicals
Authors: Augusti Rodinei , Turowski Maciej , Chen Hao , Graham Cooks R. 
Published: May 2004

AbstractIonized benzophenones ([PhC(O)PhY]+•; Y = 4 − NO2, 4 − CF3, 4‐F, 4‐Br, 4‐Me, 3,4‐diMe, 4‐OH, 4‐OMe, 2‐Cl, 2‐Me, 2‐OH, 2,6‐diMe) undergo competitive dissociation upon collision‐induced dissociation (CID) at 20 eV collision energy to generate benzoyl cations ([PhCO]+ and [YPhCO]+) and phenyl radicals (Ph• and YPh•). For the para‐substituted benzophenones, the natural logarithm of the abundance ratio of the benzoyl cations [ln([PhCO+]/[YPhCO+])] is found to correlate linearly with the calculated CO+• affinities of the phenyl radicals Ph• and YPh•. A deviation from linearity is observed for the ortho‐substituted isomers. This is probably due to a significant intramolecular steric interaction between the carbonyl group and the ortho substituent which prevents the formation of a stable planar system. An observed shift in the intercept relative to the origin is interpreted as the result of a systematic error in the calculated CO+• affinities and this effect is minimized by calculations at a higher level. The dissociation of ionized para‐substituted benzophenones is associated with a relatively high effective temperature of 1816 ± 41 K, calculated from the slope of the kinetic method plot, a value that is consistent with a covalent bond in the activated ion. In addition, Δ(ΔS), the dissociation entropy of the benzoyl cations to form CO+• and the aryl radical, is found to be about 4 J mol−1 K−1 by employing the extended version of the kinetic method. Copyright © 2004 John Wiley & Sons, Ltd.
A digital ion trap mass spectrometer coupled with atmospheric pressure ion sources
Authors: Ding Li , Sudakov Michael , Brancia Francesco L. , Giles Roger , Kumashiro Sumio 
Published: May 2004

AbstractIn a digital ion trap (DIT), the quadrupole trapping and excitation waveforms are generated by the rapid switching between discrete d.c. voltage levels. As the timing of the switch can be controlled precisely by digital circuitry, the approach provides an opportunity to generate mass spectra by means of a frequency scan in contrast to the conventional voltage scan, thus providing a wider mass range of analysis. An instrument has been constructed which employs a ‘non‐stretched’ ion trap and the field fault around the aperture of the end‐cap electrode can be corrected electronically using a field‐adjusting electrode. The ion trap was coupled with electrospray ionization (ESI) and atmospheric pressure matrix‐assisted laser desorption/ionization (AP‐MALDI) sources to demonstrate the capability of the digital method. AP‐MALDI mass spectra of singly charged ions with mass‐to‐charge ratios upto 17 000 Th were generated using a trapping voltage of only 1000 V. Forward and reverse mass scans at resolutions up to 19 000 and precursor ion isolation at resolutions up to 3500 with subsequent tandem mass spectrometric analysis were demonstrated. The method of generating the digital waveforms and period scan is described. Discussion of the issues of mass range, scan speed, ion trapping efficiency and collision‐induced dissociation efficiency are also provided. Copyright © 2004 John Wiley & Sons, Ltd.
Neuronal NOS activation during oxygen and glucose deprivation triggers cerebellar granule cell death in the later reoxygenation phase
Authors: Scorziello A. , Pellegrini C. , Secondo A. , Sirabella R. , Formisano L. , Sibaud L. , Amoroso S. , Canzoniero L.M.T. , Annunziato L. , Di Renzo G.F. 
Published: May 2004

AbstractThe present study investigated the temporal relationship between neuronal nitric oxide synthase (nNOS) activity and expression and the development of neuronal damage occurring during anoxia and anoxia followed by reoxygenation. For this purpose, cerebellar granule cells were exposed to 2 hr of oxygen and glucose deprivation (OGD) and 24 hr of reoxygenation. To clarify the consequences of nNOS activity inhibition on neuronal survival, cerebellar granule cells were exposed to OGD, both in the absence of extracellular Na+ ([Na+]e), a condition that by reducing intracellular Ca2+ ([Ca2+]I) prevents Ca2+‐dependent nNOS activation, and in the presence of selective and nonselective nNOS inhibitors, such as Nω‐L‐allyl‐L‐arginine (L‐ALA), Nω‐propyl‐L‐arginine (NPLA), and L‐nitro‐arginine‐methyl‐ester (L‐NAME), respectively. The results demonstrated that the removal of [Na+]e hampered the [Ca2+]i increase and decreased expression and activity of nNOS. Similarly, the increase of free radical production present in cerebellar neurons, exposed previously to OGD and OGD/reoxygenation, was abolished completely in the absence of [Na+]e. Furthermore, the absence of [Na+]e in cerebellar neurons exposed to 2 hr of OGD led to the improvement of mitochondrial activity and neuronal survival, both after the OGD phase and after 24 hr of reoxygenation. Finally, the exposure of cerebellar neurons to L‐ALA (200 nM), and L‐NAME (500 μM) was able to effectively reduce NO• production and caused an increase in mitochondrial oxidative activity and an improvement of neuronal survival not only during OGD, but also during reoxygenation. Similar results during OGD were obtained also with NPLA (5 nM), another selective nNOS inhibitor. These data suggest that the activation of nNOS is highly accountable for the neuronal damage occurring during the OGD and reoxygenation phases. © 2004 Wiley‐Liss, Inc.
Characteristics of the trigeminal depressor response in cats
Authors: Ohshita Naohiro , Nakajo Nobuyoshi , Takemura Motohide 
Published: May 2004

AbstractWe studied the effects of electrical stimulation of the inferior alveolar nerve (IAN) on cardiovascular responses in cats. There was statistical correlation between cardiovascular response and prestimulus mean arterial blood pressure (MABP) and heart rate (HR). A trigeminal depressor response (TDR) was induced when the prestimulus MABP and HR were above 95 mm Hg and 140 beats/min, respectively. We investigated further to identify the vasomotor regulating center and neural transmitters involved in TDR. In the medulla, electrical stimulation of the dorsomedial medulla, the infratrigeminal nucleus (IFT), and the rostral ventrolateral medulla (RVLM) induced a vasopressor response. We confirmed that neurons in the RVLM were retrogradely labeled by wheat germ agglutinin‐conjugated horseradish peroxidase injection into the nucleus intermediolateralis of the spinal cord. The vasopressor response induced by IFT stimulation was similar to that induced by IAN stimulation. Vasodepressor responses were induced when the caudal ventrolateral medulla, the nucleus tractus solitarius, the lateral tegmental field, the trigeminal nucleus interpolaris, the trigeminal spinal tract, and the paramedian reticular nucleus were stimulated. These responses, however, were not similar to the vasodepressor response induced by IAN stimulation but were similar to the cardiovascular response induced by vagal afferent stimulation. After spinalization or lesion of the RVLM, MABP and HR decreased and TDR completely disappeared. Inhibitory synaptic ligands and receptors were localized using immunohistochemical techniques. Neurons immunopositive for adrenaline, noradrenaline, and γ‐aminobutyric acid (GABA), and adrenaline α2A, GABAA, GABAB, and glycine receptors were distributed along the sympatho‐reflexive route including the RVLM and IFT. These results suggest that TDR could be induced as negative feedback to sympathetic hyperactivity whenever MABP and HR are high, because of the inhibitory control of the RVLM. © 2004 Wiley‐Liss, Inc.
Calcium signal‐mediated expression of the vasoactive intestinal polypeptide gene and its small contribution to activity‐dependent survival of mouse cerebellar granule cells
Authors: Fukuchi Mamoru , Sakuragawa Saori , Tabuchi Akiko , Tsuda Masaaki 
Published: May 2004

AbstractWe have demonstrated previously in primary cultures of mouse cerebellar granule cells (CGCs) that endogenously synthesized pituitary adenylate cyclase‐activating polypeptide (PACAP) contributes at least in part to the activity‐dependent survival of CGCs (Tabuchi et al. [2001] Neurosci. Res. 39:85–93). In this study, we have demonstrated that expression of vasoactive intestinal polypeptide (VIP), a member of the same VIP/secretin/glucagon family as PACAP, was activated markedly by Ca2+ influx through L‐type voltage‐dependent Ca2+ channels (L‐VDCCs), which could be induced under the depolarizing condition induced by high concentration of potassium (K+) in the medium. The activation of VIP mRNA expression, different from that of PACAP, was dependent partly on de novo protein synthesis. On the other hand, mRNA expression of secretin and PACAP/VIP receptors (PAC1, VPAC1, and VPAC2) was not activated by the Ca2+ influx; rather, PAC1 mRNA expression was reduced. Exogenously added VIP prevented apoptosis of CGCs under nondepolarizing conditions, the effect of which was mediated specifically through the VPAC1 receptor. Furthermore, the survival of CGCs under depolarizing conditions could be mediated partly through VPAC1, the contribution of which was much less than that of PAC1. These findings indicate that PACAP and VIP genes are coordinately activated by the Ca2+ signals in CGCs, but the contribution of VIP to the activity‐dependent survival of CGCs is quite small. © 2004 Wiley‐Liss, Inc.
Localization of wild‐type and mutant neuronal ceroid lipofuscinosis CLN8 proteins in non‐neuronal and neuronal cells
Authors: Lonka Liina , Salonen Tarja , Siintola Eija , Kopra Outi , Lehesjoki Anna‐Elina , Jalanko Anu 
Published: May 2004

AbstractNeuronal ceroid lipofuscinoses (NCLs) are a group of childhood‐onset neurodegenerative disorders characterized by accumulation of autofluorescent lipopigment in many tissues, especially in neurons. Mutations in the CLN8 gene underlie Northern epilepsy (progressive epilepsy with mental retardation [EPMR], OMIM 600143) and a subset of Turkish variant late infantile NCL, but the pathogenetic mechanisms have remained elusive. The CLN8 transmembrane protein is an endoplasmic reticulum (ER) resident protein that recycles between ER and ER‐Golgi intermediate compartment (ERGIC) in non‐neuronal cells. To explore the disease mechanisms, we have characterized the neuronal localization of wild‐type CLN8 protein as well as CLN8 proteins representing patient mutations. Semliki Forest virus‐mediated CLN8 protein localized in the ER of mouse hippocampal primary neurons when compared to subcellular markers by immunofluorescence analysis. We also analyzed the possible polarized targeting of CLN8 and observed basolateral targeting in polarized epithelial CaCo‐2 cells, suggesting that CLN8 may locate outside the ER or in a specialized subcompartment of the ER. We were not able, however, to demonstrate differential distribution of CLN8 between axons and dendrites of neurons. Fractionation of mouse brain tissue indicated that endogenous mouse Cln8 is observed in light membrane fractions, different from ER, which further suggested differential localization for CLN8 in polarized cells. The disease mutations did not affect intracellular localization of CLN8 in non‐neuronal or neuronal cells. Consequently, there is no obvious genotype–phenotype correlation at the level of protein localization and thus mutations most likely directly affect functionally important domains of CLN8. © 2004 Wiley‐Liss, Inc.
Messenger RNA and protein expression analysis of voltage‐gated potassium channels in the brain of Aβ25–35‐treated rats
Authors: Pan Yaping , Xu Xianghua , Tong Xiaoyong , Wang Xiaoliang 
Published: May 2004

AbstractPotassium channel dysfunction has been implicated in Alzheimer's disease. In the present study, the expression of voltage‐gated potassium channel (Kv) subunits in rat brain was measured after a single intracerebroventricular injection of β‐amyloid peptide 25–35 (Aβ25–35). After injection of Aβ, the spatial memory of rats was significantly impaired in the Morris water maze. Expression of five main Kv channel subunits (Kv1.5, Kv2.1, Kv1.4, Kv4.2, and Kv4.3) in mRNA level was assessed by using reverse transcription‐polymerase chain reaction (RT‐PCR). The mRNA levels of Kv2.1 and Kv1.4 were increased by 72% and 67%, respectively, in hippocampus, and Kv4.2 mRNA was increased by 58% in cortex. No other significant mRNA expression changes were found in Aβ‐treated rats. The protein expression of Kv2.1, Kv1.4, and Kv4.2 was detected by using Western blotting. Kv2.1 and Kv1.4 protein levels were increased by 48% and 50%, respectively, in hippocampus of Aβ‐treated rats, and Kv4.2 protein was increased by 42% in cerebral cortex. This study indicates that the expression up‐regulation of Kv1.4, Kv2.1, and Kv4.2 in Aβ‐induced cognitive impairment might play an important role in the pathogenesis of Alzheimer's disease. © 2004 Wiley‐Liss, Inc.
Involvement of endoplasmic reticulum Ca2+ release through ryanodine and inositol 1,4,5‐triphosphate receptors in the neurotoxic effects induced by the amyloid‐β peptide
Authors: Ferreiro Elisabete , Oliveira Catarina R. , Pereira Cláudia 
Published: May 2004

AbstractStudies with in‐vitro‐cultured neurons treated with amyloid‐β (Aβ) peptides demonstrated neuronal loss by apoptosis that is due, at least in part, to the perturbation of intracellular Ca2+ homeostasis. In addition, it was shown that an endoplasmic reticulum (ER)‐specific apoptotic pathway mediated by caspase‐12, which is activated upon the perturbation of ER Ca2+ homeostasis, may contribute to Aβ toxicity. To elucidate the involvement of deregulation of ER Ca2+ homeostasis in neuronal death induced by Aβ peptides, we have performed a comparative study using the synthetic peptides Aβ25–35 or Aβ1–40 and thapsigargin, a selective inhibitor of Ca2+ uptake into the ER. Incubation of cortical neurons with thapsigargin (2.5 μM) increased the intracellular Ca2+ levels and activated caspase‐3, leading to a significant increase in the number of apoptotic cells. Similarly, upon incubation of cortical cultures with the Aβ peptides (Aβ25–35, 25 μM; Aβ1–40, 0.5 μM), we observed a significant increase in [Ca2+]i, in caspase‐3‐like activity, and in number of neurons exhibiting apoptotic morphology. The role of ER Ca2+ release through ryanodine receptors (RyR) or inositol 1,4,5‐trisphosphate receptors (IP3R) in Aβ neurotoxicity has been also investigated. Dantrolene and xestospongin C, inhibitors of ER Ca2+ release through RyR or IP3R, were able to prevent the increase in [Ca2+]i and the activation of caspase‐3 and to protect partially against apoptosis induced by treatment with Aβ25–35 or Aβ1–40. In conclusion, our results demonstrate that the release of Ca2+ from the ER, mediated by both RyR and IP3R, is involved in Aβ toxicity and can contribute, together with the activation of other intracellular neurotoxic mechanisms, to Aβ‐induced neuronal death. This study suggests that Aβ accumulation may have a key role in the pathogenesis of AD as a result of deregulation of ER Ca2+ homeostasis. © 2004 Wiley‐Liss, Inc.
On the neurotoxicity of glutaric, 3‐hydroxyglutaric, and trans‐glutaconic acids in glutaric acidemia type 1
Authors: Lund T.M. , Christensen E. , Kristensen A.S. , Schousboe A. , Lund A.M. 
Published: May 2004

AbstractGlutaric acidemia type 1 (GA1) is an autosomal recessively inherited deficiency of glutaryl‐CoA dehydrogenase. Accumulating metabolites, 3‐hydroxyglutaric (3‐OH‐GA), glutaric (GA), and trans‐glutaconic (TG) acids, have been proposed to be involved in the development of the striatal degeneration seen in children with GA1 via an excitotoxic mechanism. We have studied the extent to which 3‐OH‐GA, GA, and TG are neurotoxic and whether neurotoxicity is caused by an excitotoxic mechanism in which 3‐OH‐GA, GA, or TG overactivates N‐methyl‐D‐aspartate (NMDA) receptors. In cultured mouse neocortical neurons, all three compounds were weakly neurotoxic, possibly through activation of NMDA receptors. However, further studies in the rat cortical wedge preparation and with NMDA receptors expressed in Xenopus oocytes could not confirm an interaction of the compounds with NMDA receptors. It is concluded that the metabolites 3‐OH‐GA, GA, and TG are only weak neurotoxins and that the neurodegenerative cascade destroying the striatum in patients with GA1 involves mainly mechanisms other than excitoxicity. © 2004 Wiley‐Liss, Inc.
Molecular mimicry: Cross‐reactive antibodies from patients with immune‐mediated neurologic disease inhibit neuronal firing
Authors: Kalume Franck , Lee Sang Min , Morcos Yvette , Callaway Joseph C. , Levin Michael C. 
Published: May 2004

AbstractRecent data indicate that molecular mimicry may play a role in the pathogenesis of human‐T‐lymphotropic virus type‐1 (HTLV‐1)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), an immune‐mediated disease of the central nervous system (CNS). Specifically, HAM/TSP patients developed antibodies that cross‐react with heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), an antigen highly expressed in neurons. Antibodies to HTLV‐1‐tax cross‐reacted with hnRNP A1, suggesting molecular mimicry between the two proteins. In support of this hypothesis, HAM/TSP IgG and antibodies to hnRNP A1 and HTLV‐1‐tax inhibited neuronal firing, suggesting that these antibodies can be pathogenic. We extended these observations by carrying out studies on over 20 different neurons. We also tested IgG isolated from six different HAM/TSP patients and two HTLV‐1 seronegative controls and added experiments that control for antibody isotype, antibody target, and neuron viability. In these studies, IgG was infused into the extracellular space during whole‐cell current clamp recordings of neurons. Our results confirm that in contrast to normal IgG, IgG from all HAM/TSP patients completely inhibited neuronal firing. Affinity‐purified antibodies specific for hnRNP A1 and a monoclonal antibody to HTLV‐1‐tax (which reacted with hnRNP A1 and whose epitope overlaps the human immunodominant epitope of tax) also inhibited neuronal firing. Monoclonal antibodies to neurofilament did not change neuronal firing. These data indicate that antibodies to neurons can be pathogenic, that biologic activity can be affected by a cross‐reactive epitope between HTLV‐1‐tax and hnRNP A1, and that molecular mimicry may play a role in the pathogenesis of HAM/TSP. © 2004 Wiley‐Liss, Inc.
Adenosine A2A receptor blockade differentially influences excitotoxic mechanisms at pre‐ and postsynaptic sites in the rat striatum
Authors: Tebano Maria Teresa , Pintor Annita , Frank Claudio , Domenici Maria Rosaria , Martire Alberto , Pepponi Rita , Potenza Rosa Luisa , Grieco Rosa , Popoli Patrizia 
Published: May 2004

AbstractAdenosine A2A receptor antagonists are being regarded as potential neuroprotective drugs, although the mechanisms underlying their effects need to be better studied. The aim of this work was to investigate further the mechanism of the neuroprotective action of A2A receptor antagonists in models of pre‐ and postsynaptic excitotoxicity. In microdialysis studies, the intrastriatal perfusion of the A2A receptor antagonist ZM 241385 (5 and 50 nM) significantly reduced, in an inversely dose‐dependent way, the raise in glutamate outflow induced by 5 mM quinolinic acid (QA). In rat corticostriatal slices, ZM 241385 (30–100 nM) significantly reduced 4‐aminopyridine (4‐AP)‐induced paired‐pulse inhibition (PPI; an index of neurotransmitter release), whereas it worsened the depression of field potential amplitude elicited by N‐methyl‐D‐aspartate (NMDA; 12.5 and 50 μM). The A2A antagonist SCH 58261 (30 nM) mimicked the effects of ZM 241385, whereas the A2A agonist CGS 21680 (100 nM) showed a protective influence toward 50 μM NMDA. In rat striatal neurons, 50 nM ZM 241385 did not affect the increase in [Ca2+]i or the release of lactate dehydrogenase (LDH) induced by 100 and 300 μM NMDA, respectively. The ability of ZM 241385 to prevent QA‐induced glutamate outflow and 4‐AP‐induced effects confirms that A2A receptor antagonists have inhibitory effects on neurotransmitter release, whereas the results obtained toward NMDA‐induced effects suggest that A2A receptor blockade does not reduce, or even amplifies, excitotoxic mechanisms due to direct NMDA receptor stimulation. This indicates that the neuroprotective potential of A2A antagonists may be evident mainly in models of neurodegeneration in which presynaptic mechanisms play a major role. © 2004 Wiley‐Liss, Inc.
Characterization of V642I‐AβPP‐induced cytotoxicity in primary neurons
Authors: Niikura Takako , Yamada Marina , Chiba Tomohiro , Aiso Sadakazu , Matsuoka Masaaki , Nishimoto Ikuo 
Published: May 2004

AbstractAmyloid precursor protein (AβPP), a precursor of amyloid β (Aβ) peptide, is one of the molecules involved in the pathogenesis of Alzheimer's disease (AD). Specific mutations in AβPP have been found in patients inheriting familial AD (FAD). These mutant AβPP proteins cause cell death in neuronal cell lines in vitro, but the molecular mechanism of cytotoxicity has not yet been clarified completely. We analyzed the cytotoxic mechanisms of the London‐type AβPP mutant, V642I‐AβPP, in primary cortical neurons utilizing an adenovirus‐mediated gene transfer system. Expression of V642I‐AβPP protein induced degeneration of the primary neurons. This cytotoxicity was blocked by pertussis toxin, a specific inhibitor for heterotrimeric G proteins, Go/i, and was suppressed by an inhibitor of caspase‐3/7 and an antioxidant, glutathione ethyl ester. A specific inhibitor for NADPH oxidase, apocynin, but not a xanthine oxidase inhibitor or a nitric oxide inhibitor, blocked V642I‐AβPP‐induced cytotoxicity. Among mitogen‐activated protein kinase (MAPK) family proteins, c‐Jun N‐terminal kinase (JNK) and p38MAPK, but not extracellular regulated kinase (ERK), were involved in this cytotoxic pathway. The V642I‐AβPP‐induced cytotoxicity was not suppressed by two secretase inhibitors, suggesting that Aβ does not play a major role in this cytotoxicity. Two neuroprotective factors, insulin‐like growth factor I (IGF‐I) and Humanin, protected these primary neurons from V642I‐AβPP‐induced cytotoxicity. Furthermore, interleukin‐6 and ‐11 also attenuated this cytotoxicity. This study demonstrated that the signaling pathway activated by mutated AβPP in the primary neurons is the same as that by the other artificial insults such as antibody binding to AβPP and the artificial dimerization of cytoplasmic domain of AβPP. The potential of neurotrophic factors and cytokines in AD therapy is also indicated. © 2004 Wiley‐Liss, Inc.