bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of the α‐ketoglutarate dehydrogenase complex by the myeloperoxidase products, hypochlorous acid and mono‐N‐chloramine
Authors: Jeitner Thomas M. , Xu Hui , Gibson Gary E. 
Published: January 2005

Abstractα‐Ketoglutarate dehydrogenase (KGDHC) complex activity is diminished in a number of neurodegenerative disorders and its diminution in Alzheimer Disease (AD) is thought to contribute to the major loss of cerebral energy metabolism that accompanies this disease. The loss of KGDHC activity appears to be predominantly due to post‐translation modifications. Thiamine deficiency also results in decreased KGDHC activity and a selective neuronal loss. Recently, myeloperoxidase has been identified in the activated microglia of brains from AD patients and thiamine‐deficient animals. Myeloperoxidase produces a powerful oxidant, hypochlorous acid that reacts with amines to form chloramines. The aim of this study was to investigate the ability of hypochlorous acid and chloramines to inhibit the activity of KGDHC activity as a first step towards investigating the role of myeloperoxidase in AD. Hypochlorous acid and mono‐N‐chloramine both inhibited purified and cellular KGDHC and the order of inhibition of the purified complex was hypochlorous acid (1×) > mono‐N‐chloramine (∼50x) > hydrogen peroxide (∼1 500). The inhibition of cellular KGDHC occurred with no significant loss of cellular viability at all exposure times that were examined. Thus, hypochlorous acid and chloramines have the potential to inactivate a major target in neurodegeneration.
Direct interaction of myosin regulatory light chain with the NMDA receptor
Authors: Amparan David , Avram Dorina , Thomas Christopher G. , Lindahl Michaela G. , Yang Jing , Bajaj Gaurav , Ishmael Jane E. 
Published: January 2005

AbstractNMDA receptors interact with a variety of intracellular proteins at excitatory synapses. In this paper we show that myosin regulatory light chain (RLC) isolated from mouse brain is a NMDA receptor‐interacting protein. Myosin RLC bound directly to the C‐termini of both NMDA receptor 1 (NR1) and NMDA receptor 2 (NR2) subunits, rendering the interaction of myosin RLC with NMDA receptors distinct from that of calmodulin which is considered a NR1‐interacting protein. Myosin RLC co‐localized with NR1 in the dendritic spines of isolated hippocampal neurons, and was co‐immunoprecipitated from brain extracts in a complex with NR1, NR2A, NR2B, PSD‐95, Adaptor protein‐2 and myosin II heavy chain. The C0 region of NR1 was necessary and sufficient for binding myosin RLC. Ca2+/calmodulin, but not calmodulin alone, displaced recombinant myosin RLC from the carboxy tail of NR1 indicating that myosin RLC and Ca2+/calmodulin can compete for a common binding site on NR1 in vitro. Myosin RLC is the only known substrate for myosin regulatory light chain kinase, which has recently been shown to modulate NMDA receptor function in isolated hippocampal neurons. Our results suggest that an additional level of NMDA receptor regulation may be mediated via a direct interaction with a light chain of myosin II. Thus, myosin RLC–NMDA receptor interactions may contribute to the contractile and motile forces that are placed upon NMDA receptor subunits during changes associated with synaptic plasticity and neural morphogenesis.
Calcium‐dependent dephosphorylation of brain mitochondrial calcium/cAMP response element binding protein (CREB)
Authors: Schuh Rosemary A. , Kristián Tibor , Fiskum Gary 
Published: January 2005

AbstractCalcium‐mediated signaling regulates nuclear gene transcription by calcium/cAMP response element binding protein (CREB) via calcium‐dependent kinases and phosphatases. This study tested the hypothesis that CREB is also present in mitochondria and subject to dynamic calcium‐dependent modulation of its phosphorylation state. Antibodies to CREB and phosphorylated CREB (pCREB) were used to demonstrate the presence of both forms in isolated mitochondria and mitoplasts from rat brain. When energized mitochondria were exposed to increasing concentrations of Ca2+ in the physiological range, pCREB was lost while total CREB remained constant. In the presence of Ru360, an inhibitor of the mitochondrial Ca2+ uptake uniporter, calcium‐dependent loss of pCREB levels was attenuated, suggesting that intramitochondrial calcium plays an important role in pCREB dephosphorylation. pCREB dephosphorylation was not, however, inhibited by the phosphatase inhibitors okadaic acid and Tacrolimus. In the absence of Ca2+, CREB phosphorylation was elevated by the addition of ATP to the mitochondrial suspension. Exposure of mitochondria to the pore‐forming molecule alamethicin that causes osmotic swelling and release of intermembrane proteins enriched mitochondrial pCREB immunoreactivity. These results further suggest that mitochondrial CREB is located in the matrix or inner membrane and that a kinase and a calcium‐dependent phosphatase regulate its phosphorylation state.
Group I and II metabotropic glutamate receptors alter brain cortical metabolic and glutamate/glutamine cycle activity: a 13C NMR spectroscopy and metabolomic study
Authors: Rae Caroline , El‐Hajj Moussa Charbel , Griffin Julian L. , Bubb William A. , Wallis Trent , Balcar Vladimir J. 
Published: January 2005

AbstractMetabotropic glutamate receptors (mGluR) modulate neuronal function. Here, we tested the effect on metabolism of a range of Group I and II mGluR ligands in Guinea pig brain cortical tissue slices, applying 13C NMR spectroscopy and metabolomic analysis using multivariate statistics. The effects of Group I agonists (S)‐3,5‐dihydroxyphenylglycine (DHPG) and (RS)‐2‐chloro‐5‐hydroxyphenylglycine (CHPG) depended upon concentration and were mostly stimulatory, increasing both net metabolic flux through the Krebs cycle and glutamate/glutamine cycle activity. Only the higher (50 µm) concentrations of CHPG had the opposite effect. The Group I antagonist (RS)‐1‐aminoindan‐1,5‐dicarboxylic acid (AIDA), consistent with its neuroprotective role, caused significant decreases in metabolism. With principal components analysis of the metabolic profiles generated by these ligands, the effects could be separated by two principal components. Agonists at Group II mGluR [(2S,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)glycine (DCG IV) and 2R,4R‐4‐aminopyrrolidine‐2,4‐dicarboxylate (APDC)] generally stimulated metabolism, including glutamate/glutamine cycling, although this varied with concentration. The antagonist (2S)‐α‐ethylglutamic acid (EGLU) stimulated astrocyte metabolism with minimal impact on glutamate/glutamine cycling. (RS)‐1‐Aminophosphoindan‐1‐carboxylic acid (APICA) decreased metabolism at 5 µm but had a stimulatory effect at 50 µm. All ligand effects were separated from control and from each other using two principal components. The ramifications of these findings are discussed.
Role of basic region leucine zipper transcription factors cyclic AMP response element binding protein (CREB), CREB2, activating transcription factor 2 and CAAT/enhancer binding protein α in cyclic AMP response element‐mediated transcription
Authors: Thiel Gerald , Al Sarraj Jude , Vinson Charles , Stefano Luisa , Bach Karl 
Published: January 2005

AbstractThe transcription factor cAMP response element binding protein (CREB), a member of the basic region leucine zipper (bZIP) family of proteins, is the major cAMP response element (CRE) binding. Other bZIP proteins, including CREB2, activating transcription factor 2 (ATF2), or CAAT/enhancer binding protein (C/EBP) have been reported to transactivate CRE‐containing genes or to interfere with transactivation by CREB. We have designed a simple transactivation assay using expression of either a constitutively active CREB mutant or a nuclear targeted mutant of the catalytic subunit of cAMP‐dependent protein kinase. In both cases, a striking stimulation of transcription of CRE‐containing reporter genes was observed in noradrenergic locus coeruleus‐like CATH.a cells. In addition, a constitutively active mutant of ATF2 specifically transactivated a secretogranin II promoter/luciferase reporter gene, but had no effect on the tyrosine hydroxylase promoter. In contrast, CREB2 and C/EBPα did not transactivate CRE‐containing reporter genes, indicating that these bZIP proteins target distinct genetic elements. Experiments involving dominant‐negative bZIP mutants revealed that CREB does not heterodimerize with CREB2, ATF2, c‐Jun or C/EBP. Rather, CREB and ATF2 compete for binding to the CRE, and are independently able to up‐regulate transcription of genes containing CRE motifs in their regulatory regions.
Charge selectivity of the Cys‐loop family of ligand‐gated ion channels
Authors: Jensen Marianne L. , Schousboe Arne , Ahring Philip K. 
Published: January 2005

AbstractThe determinants of charge selectivity of the Cys‐loop family of ligand‐gated ion channels have been studied for more than a decade. The investigations have mainly covered homomeric receptors e.g. the nicotinic acetylcholine receptor α7, the glycine receptor α1 and the serotonin receptor 5‐HT3A. Only recently, the determinants of charge selectivity of heteromeric receptors have been addressed for the GABAA receptor α2β3γ2. For all receptor subtypes, the selectivity determinants have been located to an intracellular linker between transmembrane domains M1 and M2. Two features of the M1–M2 linker appear to control ion selectivity. A central role for charged amino acid residues in selectivity has been almost universally observed. Furthermore, recent studies point to an important role of the size of the narrowest constriction in the pore. In the present review, these determinants of charge selectivity of the Cys‐loop family of ligand‐gated ion channels will be discussed in detail.
Multifocal electroretinography in isolated arterially perfused bovine eye
Authors: Shahidullah Mohammad , Chan Henry H. L. , Yap Maurice K. , Liu Quan , To Chi‐Ho 
Published: January 2005

AbstractAim:  To develop an isolated arterially perfused bovine eye as an in vitro model for studying retinal electrophysiology using multifocal electroretinography (mfERG).Methods:  Fresh bovine eyes were cannulated through the ophthalmic artery and perfused with oxygenated Krebs’ solution at 37°C within 15 min postmortem. Multifocal ERG was recorded using the veris 1.0 (Visual Evoked Response Imaging System).Results:  The mfERG waveform of in vitro bovine eyes had a typical trough (negative wave, N1) and peak (positive wave, P1) similar to those of human mfERG. The implicit times (peak latencies) for N1 and P1 were 20 and 42 ms respectively, and the average response amplitude (N1P1) was 55 nV. The implicit times of N1 and P1 were maintained for more than 4 h. The mfERG responses were affected proportionately by the stimulus intensity. Without a neutral density filter, the mean response amplitude was about 55 nV, which was diminished to 26, 18 and 10 nV under neutral density filters of 0.4, 1.0 and 1.4, respectively. Partial occlusion of the pupil completely abolished mfERG responses from the corresponding part of the retina.Conclusions:  Isolated arterially perfused bovine eye may be used as an experimental model to study retinal electrophysiology using mfERG. The in vitro eye may offer a convenient and easily obtainable alternative to live animals, particularly for drug screening and invasive studies.
When Practice Oversteps the Limits of Theory: An Assessment of Fair Media Coverage for Political Parties in Great Britain and Mexico
Authors: Mena David 
Published: January 2005

AbstractOver stressing the rights‐safeguarding role of democracy has led to a widespread neglect of democracy's essential function: to ensure the legitimacy of elected rulers and by doing so, to ensure political stability. The effects of this neglect are apparent in the disputes that arise concerning media coverage of elections. This article examines the difficulties democratic statesmen face to justify and consistently implement arrangements that limit the freedom of expression of the media in order to minimize the challenges to the legitimacy of electoral outcomes that a biased coverage of elections could incite. Current democratic theory does not address this problem. Indeed its emphasis on safeguarding the rights of citizens can suggest that the freedom of expression of the media should prevail over considerations of legitimacy and stability. This study examines the justifications adduced, and the implementation of, arrangements that curtail the right to advocacy of broadcasters and limit their right to editorial discretion in order to provide political parties with what I refer to here as “fair media coverage.” In particular, the article highlights and assesses the experiences in fair media coverage of election campaigns in the British General Election of 1997 and the Mexican Federal Election of 2000. In full view of these case studies, and on the basis of the theoretical guidelines I develop at the beginning of this article, I argue for limiting freedom of expression and stress the urgent need for democratic theories to address the practical problems that trouble democratic authorities.
“Like Butter Scraped over Too Much Bread”: Animal Protection Policy in Mexico1
Authors: Norman Emma R. , Hernández Norma Contreras 
Published: January 2005

AbstractOver the past fifteen years Mexico has developed a string of comprehensive animal protection regulations designed to address the serious problems that affect both wild and domestic animals in the territory. Yet for all their detailed coherence and despite serious government efforts, the regulations continue to lack effective enforcement and authorities are increasingly overstretched. This study discusses three key areas that obstruct the effective implementation of Mexican animal protection policy, but where advances could be feasibly initiated. The first concerns deficiencies at the political level. The second addresses the awkward relation between government and civil society on the issue. The third examines the scope of the problem in Mexico and some implications this has for international involvement. Finally the study suggests a more collaborative approach for implementing the policy that attempts to address central concerns in each of the three areas considered.
Various immunostaining patterns of CD31, CD34 and endoglin and their relationship with lymph node metastasis in oral squamous cell carcinomas
Authors: Nagatsuka Hitoshi , Hibi Kazuteru , Gunduz Mehmet , Tsujigiwa Hidetsugu , Tamamura Ryou , Sugahara Toshio , Sasaki Akira , Nagai Noriyuki 
Published: January 2005

Background:  Intratumoral blood vessels are known to play an important role in cancer growth and metastasis. The discrepancy in previous reports using various endothelial markers individually suggested us to investigate both normal and various tumor areas with a wide panel of vascular markers.Methods:  Here, we used a panel of three antibodies (CD31, CD34, and endoglin) as blood vessel markers to investigate the distribution and properties of blood vessels in normal oral tissues and squamous cell carcinomas.Results:  Many microvessels with strong remodeling activity as well as undifferentiated tumoral vascular endothelial cells and immature endothelial cells were present in the cancer cell nest and marginal area of cancer infiltration. Our results showed different vascular distribution patterns using various immunostaining markers in normal and tumoral tissues.Conclusion:  Vascular distribution and properties of endothelial cells appear to be closely associated with metastasis.
Quantitative histological features and ultrastructure of opercula of human teeth showing normal and delayed eruption
Authors: Verma D. K. , Nair P. N. R. , Luder H. U. 
Published: January 2005

Background:  Failure of eruption of human permanent molars has been attributed to opercular lesions, although comparisons with specimens from normally erupting teeth are scarce. The aim of this study was to quantitatively analyse opercula associated with normal and delayed tooth eruption.Method:  Twenty opercula covering permanent molars delayed in eruption were obtained from 13 patients aged 7.3–18.1 years. Six opercula from normally erupting molars of five 7.3–17.5‐year‐old subjects served as controls. Specimens were analysed light and electron microscopically and morphometrically.Results:  In addition to features recognized previously, prominent numbers of nerves, high endothelial‐like venules and mast cells were observed. Ultrastructurally, large multinucleated cells did not reveal cell boundaries running between the nuclei, and mast cells seemed belonging to the MCTC‐type. None of the features differed significantly between opercula from cases of delayed and normal tooth eruption.Conclusions:  Disturbances of tooth eruption that are attributed to opercular lesions may represent retentions resulting from the failure of the eruption mechanism, rather than impactions because of a physical barrier.
Enhanced Bax in oral SCC in relation to antitumor effects of chemotherapy
Authors: Takemura Kanako , Noguchi Makoto , Ogi Kazuhiro , Tokino Takashi , Kubota Hiromi , Miyazaki Akihiro , Kohama Geniku , Hiratsuka Hiroyoshi 
Published: January 2005

Background:  Antitumor effects of chemotherapeutic agents are commonly associated with the induction of apoptosis. Bax belongs to the Bcl‐2 family and induces apoptosis. The present study was conducted to investigate the relationship between enhanced Bax expression in oral squamous cell carcinoma (SCC; cell lines and clinical cases) and the antitumor effects of chemotherapy.Methods:  In three oral SCC cell lines, Bax expression before and after treatment with chemotherapeutic agents [docetaxel (TXT), cisplatin and 5‐fluorouracil] was examined by reverse transcriptase‐polymerase chain reaction and immunoblotting. The effects of treatment were assessed by counting the number of viable cells and determining sub‐G1 cells. Tissue samples (both biopsy specimens before chemotherapy and surgically excised specimens after chemotherapy) from nine patients with oral SCC who underwent neoadjuvant chemotherapy were immunostained for Bax. The relationship between enhancement of Bax expression and chemotherapeutic effects was established.Results:  Two of three cell lines did not express Bax mRNA or protein before treatment. After treatment, Bax expression was enhanced only by TXT in one cell line, but by all chemotherapeutic agents in the other two cell lines. In three of nine patients, Bax expression was not found before chemotherapy. Two of these three patients showed enhanced Bax expression after chemotherapy including TXT, but one still failed to express Bax. Both in cell lines and clinical cases, enhancement of Bax after chemotherapy was associated with antitumor effects.Conclusion:  Certain chemotherapeutic agents enhance Bax expression in oral SCC, and it is suggested that this contributes to the antitumor effects of chemotherapy.
Avascular jaw osteonecrosis in association with cancer chemotherapy: series of 10 cases
Authors: Bagan J. V. , Murillo J. , Jimenez Y. , Poveda R. , Milian M. A. , Sanchis J. M. , Silvestre F. J. , Scully C. 
Published: January 2005

Background:  We present a series of 10 patients with osteonecrosis of the jaws (ONJ) that appeared following cancer chemotherapy.Material and methods:  Of the 10 cases with ONJ, six had bone metastases from breast cancers and the other four had multiple myeloma. We analysed the location of bone metastases, as well as the characteristics of the ONJ, and the drugs with which they had been treated for their bone metastases.Results:  Of the 10 patients, all had ONJ in the mandible; 50% also had maxillary involvement. The average number of areas of painful exposed was 2.1 per patient (range 1–5). In seven patients a tooth extraction preceded the onset of ONJ. Two patients developed oroantral communications and another a cutaneous fistula to the neck with suppuration. In all the 10 patients the histopatholological diagnosis was of chronic osteomyelitis without evidence of metastatic disease to the jaws. All the patients had received treatment for their malignant bone disease with bisphosphonates. These were the only drugs that all patients had received.Conclusion:  ONJ appears to have a relationship with the use of bisphosphonates.
Oxpentifylline is not effective for symptomatic oral lichen planus
Authors: Wongwatana Sasiwong , Leao Jair C. , Scully Crispian , Porter Stephen 
Published: January 2005

Background:  There are no reliably effective therapies for oral lichen planus (OLP). The aim of the present work was to determine the potential efficacy of oxpentifylline in the management of OLP.Methods:  Fifteen patients (six males, median age for the group 52 years, ranging from 33 to 72) with clinically and histopathologically confirmed OLP were treated with oxpentifylline at a dose of 400 mg three times daily.Results:  Only 10 patients completed an 8 week course, the other five having to stop therapy because of adverse effects. Only three patients had any relief of their signs and symptoms of OLP.Conclusion:  The results indicate that oxpentifylline is unlikely to be of benefit for the treatment of OLP.
Emdogain® does not prevent progressive root resorption after replantation of avulsed teeth: a clinical study
Authors: Schjøtt M. , Andreasen J. O. 
Published: January 2005

Abstract –  Emdogain® has been shown in clinical and experimental studies to promote regeneration of all periodontal tissues: cementum with anchoring fibres, a functional, periodontal ligament and alveolar bone in connection with treatment of marginal periodontitis.The intention of this study was to analyse whether this regenerative capacity upon the periodontal ligament also worked in a trauma situation where a significant number of PDL cells have been eliminated because of unphysiologic storage or actual damage during avulsion or replantation. Furthermore if ankylosis sites already established because of earlier replantation after avulsion could be surgical removed and application of Emdogain® could revert the ankylosis stage to a normal PDL situation. The first treatment situation was tested in seven patients with a total of 16 avulsed teeth with varying time of extra oral storage. The teeth were extra‐orally endodontically treated and the root and socket covered with Emdogain® before replantation. All teeth demonstrated subsequent ankylosis, primarily diagnosed by a percussion test. The second treatment situation where an ankylosis was already established constituted of seven patients with a total of 11 teeth because of previous replantation after avulsion. These teeth were all extracted, the ankylosis sites removed and the root and socket treated with Emdogain®. After 6 months all teeth showed recurrence of ankylosis. It is concluded that Emdogain® was not able to prevent or cure ankylosis.