bluuebunny/crossref_metadata_2025_split huggingface dataset:
Further evidence that the CCK2receptor is coupled to two transduction pathways using site‐directed mutagenesis
Authors: Pommier Blandine , Marie‐Claire Cynthia , Da Nascimento Sophie , Wang Hung‐Li , Roques Bernard P. , Noble Florence 
Published: February 2008

AbstractA heterogeneity of CCK2receptors has been reported which could correspond to different states of coupling to G proteins and/or association with different second messenger systems. To investigate these hypotheses, the wild‐type CCK2receptor and three mutants F347A, D100N and K333M/K334T/R335L, expected to modify the coupling of the G protein with the third intracellular loop of the receptor, were transfected into Cos‐7 cells and their binding and signalling properties were evaluated using the natural ligand CCK8. Activation of wild‐type as well as F347A, D100N or K333M/K334T/R335L CCK2receptors by this ligand led to a similar arachidonic acid release which was blocked by pertussis toxin and the phospholipase A2inhibitor, mepacrine. Nevertheless, in contrast to the wild‐type CCK2receptor, addition of CCK8to cells transfected with the F347A or K333M/K334T/R335L mutants did not result in the production of inositol phosphates while the maximum increase in this second messenger formation was reduced by 30% with the D100N mutant. Taken together, these results suggest that the CCK2receptor is coupled to two G proteins and that Phe347 and the cluster of basic residues K333/K334/R335 probably play a key role in Gqprotein stimulation leading to inositol phosphate production but not in activation of the G protein coupled to phospholipase A2. These data bring additional support at the molecular level to the existence of different affinity states of CCK2receptors suggested from the results of binding assays and behavioural studies.
Noradrenergic depletion increases inflammatory responses in brain: effects on IκB and HSP70 expression
Authors: Heneka Michael T. , Gavrilyuk Vitaliy , Landreth Gary E. , O'Banion M. Kerry , Weinberg Guy , Feinstein Douglas L. 
Published: February 2008

AbstractThe inflammatory responses in many cell types are reduced by noradrenaline (NA) binding to β‐adrenergic receptors. We previously demonstrated that cortical inflammatory responses to aggregated amyloid beta (Aβ) are increased if NA levels were first depleted by lesioning locus ceruleus (LC) noradrenergic neurons, which replicates the loss of LC occurring in Alzheimer's disease. To examine the molecular basis for increased responses, we used the selective neurotoxin DSP4 to lesion the LC, and then examined levels of putative anti‐inflammatory molecules. Inflammatory responses were achieved by injection of aggregated Aβ1–42 peptide and IL‐1β into frontal cortex, which induced neuronal inducible nitric oxide synthase (iNOS) and microglial IL‐1β expression. DSP4‐treatment reduced basal levels of nuclear factor kappa B (NF‐κB) inhibitory IκB proteins, and of heat shock protein (HSP)70. Inflammatory responses were prevented by co‐injection (ibuprofen or ciglitzaone) or oral administration (pioglitazone) of peroxisome proliferator‐activated receptor gamma (PPARγ) agonists. Treatment with PPARγ agonists restored IκBα, IκBβ, and HSP70 levels to values equal or above those observed in control animals, and reduced activation of cortical NF‐κB. These results suggest that noradrenergic depletion reduces levels of anti‐inflammatory molecules which normally limit cortical responses to Aβ, and that PPARγ agonists can reverse that effect. These findings suggest one mechanism by which PPARγ agonists could provide benefit in neurological diseases having an inflammatory component.
Photic regulation of heme oxygenase activity in the golden hamster retina: involvement of dopamine
Authors: Sacca Geraldine B. , Sáenz Daniel A. , Jaliffa Carolina O. , Minces Luciana , Sarmiento María I. Keller , Rosenstein Ruth E. 
Published: February 2008

AbstractThe photic regulation of heme oxygenase (HO) activity was examined in the golden hamster retina. This enzymatic activity was significantly higher at midday than at midnight. When the hamsters were placed under constant darkness for 48 h and killed at subjective day or at subjective night, the differences in HO activity disappeared. Western blot analysis showed no differences in HO levels among these time points. Dopamine significantly increased this activity in retinas excised at noon or at midnight, with a higher sensitivity at night. The effect of dopamine was reversed by SCH 23390 but not by spiperone and clozapine and it was not reproduced by quinpirole.In vitro, the increase in HO activity found in retinas incubated under light for 1 h was significantly reduced by SCH 23390. Two cAMP analogs increased HO activity and their effect, as well as the effect of dopamine was blocked by H‐89, a protein kinase A (PKA) inhibitor. Tin protoporphyrin IX, an HO inhibitor, significantly decreased cGMP accumulation with maximal effects during the day. Low concentrations of bilirubin decreased retinal thiobarbituric acid substances levels (an index of lipid peroxidation) in basal conditions and after exposing retinal cells to H2O2. These results suggest that hamster retinal HO activity is regulated by the photic stimulus, probably through a dopamine/cAMP/PKA dependent pathway.
SKF83959 selectively regulates phosphatidylinositol‐linked D1 dopamine receptors in rat brain
Authors: Jin Li‐Qing , Goswami Satindra , Cai Guoping , Zhen Xuechu , Friedman Eitan 
Published: February 2008

AbstractPreviously a distinct D1‐like dopamine receptor (DAR) that selectively couples to phospholipase C/phosphatidylinositol (PLC/PI) was proposed. However, lack of a selective agonist has limited efforts aimed at characterizing this receptor. We characterized the in vitro and in vivo effects of SKF83959 in regulating PI metabolism. SKF83959 stimulates (EC50, 8 µm) phosphatidylinositol 4,5‐biphosphate hydrolysis in membranes of frontal cortex (FC) but not in membranes from PC12 cells expressing classical D1A DARs. Stimulation of FC PI metabolism was attenuated by the D1 antagonist, SCH23390, indicating that SKF83959 activates a D1‐like DAR. The PI‐linked DAR is located in hippocampus, cerebellum, striatum and FC. Most significantly, administration of SKF83959 induced accumulations of IP3 in striatum and hippocampus. In contrast to other D1 DAR agonists, SKF83959 did not increase cAMP production in brain or in D1A DAR‐expressing PC12 cell membranes. However, SKF83959 inhibited cAMP elevation elicited by the D1A DAR agonist, SKF81297, indicating that the compound is an antagonist of the classical D1A DAR. Lastly, we demonstrated that SKF83959 enhances [35S]guanosine 5′‐O‐(3‐thiotriphosphate) binding to membrane Gαq and Gαi proteins, suggesting that PI stimulation is mediated by activation of these guanine nucleotide‐binding regulatory proteins. Results indicate that SKF83959 is a selective agonist for the PI‐linked D1‐like DAR, providing a unique tool for investigating the functions of this brain D1 DAR subtype.
MISSBRAUCH VON BENZODIAZEPINDERIVATEN BEI ALKOHOLKRANKEN*
Authors: KRYSPIN‐EXNER K. 
Published: February 2008

Zusammenfassung—Seit der Einführung der Benzodiazepine in die psychiatrische Therapie wurden diese Substanzen im weiten Bereich zur Therapie von Alkoholkranken verwendet. Um festzustellen welche Suchtgefährdung diese Substanzen beinhalten. wurden 491 ambulant behandelte Alkoholiker in der Alkoholabstinenz in dieser Hinsicht einer genauen Untersuchung unterzogen. 111 dieser Patienten waren auf Chlordiazepoxyd und 302 auf Diazepam eingestellt. Über die dabei beobachteten Fälle von Sucht und Mißbrauch wird berichtet. wobei ein Fall von Chlordiaz‐epoxydmißbrauch und ein Fall von Diazepamsucht mit einem schweren Entziehungssyndrom ausführlich beschrieben werden. Es wird auf den zum Unterschied von der Barbituratsucht und Alkoholsucht unterschiedlichen Mechanismus des Tranquilizer‐Mißbrauches hingewiesen. Die selbstaggressiven Tendenzen, die dazu führen sind geringer ausgeprägt. Den Tranquilizern fehlt die primär euphorisierende Wirkung. Die klinischen Bilder der Suchtfälle erreichen nicht den Schweregrad der Barbituratsucht. Die Rückbildung der Ausfallserscheinungen geht wesentlich rascher vor sich und ist in allen Fällen vollständig. Es besteht daher keine Kontraindikation zur Verwendung der Benzodiazepine bei den an sich suchtgefährdeten Alkoholkranken, doch ist eine regelmäßige ärztliche Kontrolle, der unter Benzodiazepinmedikation stehenden Patienten erforderlich. Polytoxikomane sollten nicht mit Tranquilizern behandelt werden.
The Use of Methadone for Narcotic Blockade
Authors: DOLE VINCENT P. , NYSWANDER MARIE E. 
Published: February 2008

Résumé— Methadone, une drogue narcotique, peut être utilisée comme un agent antinarcotique s'il est administré aux patients dans une dose constante, orale, journalière. La drogue bloquée, les intoxiqués à l'héroine ne peuvent plus l'utiliser pour obtenir l'euphorie. Ils sont dans un état normal fonctionnel et sont capables de devenir des membres responsables de leur communauté. En traitant 750 cas d'intoxiqués á l'héroine, tenaces, dans les quatres dernières années, on a eu 90% de succès.Zusammenfassung— Methadon, eine narkotische Medizin, kann als antinarkotisches Mittel verwendent werden, wenn es Patienten in gleichbleibenden, oralen, täglichen Dosen verabreicht wird. Derartig blockierte Heroinsüchtige können dieses Rauschgift nicht mehr zur Erzielung von Euphorie benützen. Sie befinden sich in einem normalen, funktionellen Zustand und sind in der Lage, verantwortungsvolle Mitglieder ihrer Gemeinschaft zu werden. Mit dieser Behandlung wurde ein 90% Erfolg bei 750 eingefleischten Heroinsüchtigen während der vergangenen vier Jahre erzielt.
Acute megakaryoblastic leukaemia (AMKL) in children: a comparison of AMKL with and without Down syndrome
Authors: Hama Asahito , Yagasaki Hiroshi , Takahashi Yoshiyuki , Nishio Nobuhiro , Muramatsu Hideki , Yoshida Nao , Tanaka Makito , Hidaka Hirokazu , Watanabe Nobuhiro , Yoshimi Ayami , Matsumoto Kimikazu , Kudo Kazuko , Kato Koji , Horibe Keizo , Kojima Seiji 
Published: February 2008

SummaryTo characterize childhood acute megakaryoblastic leukaemia (AMKL), we reviewed 45 children with AMKL diagnosed between 1986 and 2005 at Nagoya University Hospital and Japanese Red Cross Nagoya First Hospital. Twenty‐four patients (53%) had AMKL associated with Down syndrome (DS‐AMKL) and 21 (47%) had non‐DS‐AMKL. The median age of the DS‐AMKL patients was 21 months (range, 8–38 months) and that of non‐DS‐AMKL patients was 15 months (range, 2–185 months). The morphology of blast cells was categorized into three groups according to the stage of megakaryocyte maturation. The blast cells were more immature in DS‐AMKL than in non‐DS‐AMKL in terms of morphology and immunophenotyping. Cytogenetic abnormalities of leukaemic cells were classified into seven categories: normal karyotype including constitutional trisomy 21 in DS‐AMKL; numerical abnormalities only; t(1;22)(p13;q13); 3q21q26 abnormalities; t(16;21)(p11;q22); −5/del(5q) and/or −7/del(7q); and other structural changes. The outcome of children with either DS‐AMKL or non‐DS‐AMKL is excellent. The 10‐year overall survival estimate was 79% [95% confidence interval (CI): 54–90] for DS‐AMKL and 76% (95% CI: 58–91) for non‐DS‐AMKL (P = 0·81) with a median follow‐up of 78 months (range, 20–243 months). Our study shows the diverse heterogeneity of childhood AMKL and the need for subclassification according to cytogenetic and morphological features.
The influence of clients' perceptions of the helping relationship in the development of an empathy scale
Authors: REYNOLDS B. 
Published: February 2008

The paper includes a discussion about the origins of items on a measure of cognitive–behavioural empathy. This scale was originally produced by the author as a teaching tool for an empathy education programme (for RNs) and subsequently developed into a quantitative measure of empathy. The instrument is being used as part of a triangulated approach for data collection on research into the effectiveness of an educational programme about registered nurses' empathy.Antecedents of the initial item pool for the scale stem from theoretical views about empathy, the professional experience of others, and the researcher's experience with clients. While this scale has undergone some investigation for reliability and validity, this work will only be summarized briefly. The major focus for the paper is clients' reports of interpersonal conditions which they perceive as being helpful, or unhelpful, in respect of building therapeutic nurse–client relationships.
Stories about living in a hospital ward as narrated by schizophrenic patients
Authors: PEJLERT A. , ASPLUND K. , NORBERG A. 
Published: February 2008

Stories about living in a hospital ward as narrated by schizophrenic patientsTen schizophrenic patients were interviewed about their own experiences of life in a hospital ward, of their care provider and of the care received. The interview texts were analysed using a phenomenological hermeneutic method. Fatigue, thinking about problems/inner activities, relations and longings for the pre‐illness days were themes that occurred in the stories. Seven of the ten interviewees stated that they suffered from fatigue. They were preoccupied with an inner dialogue, trying to solve problems on their own. The patients were alone in their stories. The problems that the patients expressed with regard to relationships arose because they both longed for and feared contact with others, and they felt that they were not ‘themselves’ when they were with others. For developing care, the importance of learning more about the patients' experiences, especially regarding fatigue, is emphasized.
Schizophrenic patients' image of their carers and the carers' image of their patients: an interview study
Authors: HELLZENRN O. , NORBERGRN A. , SANDMANRN P.O. 
Published: February 2008

Schizophrenic patients' image of their carers and the carers' image of their patients: an interview studyIn order to gain a deeper understanding of how long‐term adult schizophrenic patients perceive themselves, their carers and the care they receive in relation to how the carers perceive their patients, themselves and the care they provide, a narrative interview study, analysed using a method inspired by Ricoeur's philosophy, was performed. The main findings of this study were that both patients and carers who saw the patients as a subject stressed the confirming relation between the parties as an essential element of the care. The carers who saw the patient as an object did not share this opinion. They had a more restricted point of view, seeing their goal only as providing a variety of care activities and keeping the schizophrenic patients at the hospital. This study also points out that confirmation is provided in the meeting between patient and carers.
Revisiting the nursing management of the psychopath
Authors: MORAN T. , MASON T. 
Published: February 2008

Revisiting the nursing management of the psychopathThere has been a growing concern regarding the treatability of those patients labelled as psychopathically disordered. Notwithstanding this important debate, and the ultimate outcome of it, the nursing management of this categorized legal group continues on a daily basis. This paper contributes a theoretical foundation to the practicalities of nursing this particularly difficult patient group, based upon clinical experience, and offers a nursing perspective to the complexities of the debate.
The Tao, social constructionism and psychiatric nursing practice and research
Authors: STEVENSON C. 
Published: February 2008

A foreword to the abstract/introductionFor the reader who is more accustomed to the standard form of academic papers, it seemed necessary to prepare the ground for a more discursive presentation that does not follow the conventions of, for example, using the third person or summarizing the paper initially. If conventions are simply customs agreed amongst people then the academic ‘form’ can be put in parentheses for this paper, for this journal, for…?–‘… Scholarly Dissertations contain no more of the character of Taoist wisdom than does the typical wax museum’ (Hoff 1982, p. 26).1
Nitrate signalling mediated by the NRT1.1 nitrate transporter antagonises l‐glutamate‐induced changes in root architecture
Authors: Walch‐Liu Pia , Forde Brian G. 
Published: February 2008

SummaryArabidopsis root architecture is highly responsive to changes in the nitrogen supply. External NO3− stimulates lateral root growth via a signalling pathway involving the ANR1 MADS box transcription factor, while the presence of exogenous l‐glutamate (Glu) at the primary root tip slows primary root growth and stimulates root branching. We have found that NO3−, in conjunction with Glu, has a hitherto unrecognized role in regulating the growth of primary roots. Nitrate was able to stimulate primary root growth, both directly and by antagonising the inhibitory effect of Glu. Each response depended on direct contact between the primary root tip and the NO3−, and was not elicited by an alternative N source (NH4+). The chl1‐5 mutant, which is defective in the NRT1.1 (CHL1) NO3− transporter, was insensitive to NO3− antagonism of Glu signalling, while an anr1 mutant retained its sensitivity. Sensitivity to NO3− was restored in a chl1‐5 mutant constitutively expressing NRT1.1. However, expression in chl1‐5 of a transport‐competent but non‐phosphorylatable form of NRT1.1 not only failed to restore NO3− sensitivity but also had a dominant‐negative effect on Glu sensitivity. Our results indicate the existence of a NO3− signalling pathway at the primary root tip that can antagonise the root’s response to Glu, and they further suggest that NRT1.1 has a direct NO3− sensing role in this pathway. We discuss how the observed signalling interactions between NO3− and Glu could provide a mechanism for modulating root architecture in response to changes in the relative abundance of organic and inorganic N.
Heparan sulphate proteoglycans in glia and in the normal and injured CNS: expression of sulphotransferases and changes in sulphation
Authors: Properzi Francesca , Lin Rachel , Kwok Jessica , Naidu Murali , Van Kuppevelt Toin H. , Ten Dam Gerdy B. , Camargo Luiz M. , Raha‐Chowdhury Ruma , Furukawa Yoko , Mikami Tadahisa , Sugahara Kazuyuki , Fawcett James W. 
Published: February 2008

AbstractHeparan sulphate proteoglycans (HSPGs) have multiple functions relevant to the control of the CNS injury response, particularly in modulating the effects of growth factors and localizing molecules that affect axon growth. We examined the pattern of expression and glycanation of HSPGs in the normal and damaged CNS, and in astrocytes and oligodendrocyte precursors because of their participation in the injury reaction. The composition of HS glycosaminoglycan (GAG) chains was analysed by biochemical analysis and by the binding of antibodies that recognize sulphated epitopes. We also measured levels of HS sulphotransferases and syndecans. Compared with oligodendrocytes, oligodendrocyte precursors have more 2‐O‐sulphation in their HS GAG. This is accompanied by higher expression of the enzyme responsible for 2‐O‐sulphation, HS 2‐O‐sulphotransferase (HS2ST) and a fall in syndecan‐1. Astrocytes treated with tumour growth factor (TGF)α or TGFβ to mimic the injury response showed upregulation of syndecan‐1 and HS2ST correlating with an increase in 2‐O‐sulphate residues in their HS GAGs. This also correlated with increased staining with AO4B08 anti‐GAG antibody that recognizes high sulphation, and reduced staining with RB4EA12 recognizing low sulphation. After injury to the adult rat brain there was an overall increase in the quantity of HSPG around the injury site, mRNA for HS2ST was increased, and the changes in staining with sulphation‐specific antibodies were consistent with an increase in 2‐O‐sulphated HS. Syndecan‐1 was upregulated in astrocytes. The major injury‐related change, seen in injured brain and cultured glia, was an increase in 2‐O‐sulphated HS and increased syndecan‐1, suggesting novel approaches to modulating scar formation.
Characterisation of the zebrafish serotonin transporter functionally links TM10 to the ligand binding site
Authors: Severinsen Kasper , Sinning Steffen , Müller Heidi Kaastrup , Wiborg Ove 
Published: February 2008

AbstractThe selective serotonin reuptake inhibitors and tricyclic antidepressants act by inhibiting pre‐synaptic reuptake of serotonin (5‐HT) leading to elevated synaptic 5‐HT concentrations. However, despite extensive efforts little is known about the protein‐ligand interactions of serotonin transporter (SERT) and inhibitors. To identify domains and individual amino acids important for ligand binding, we cloned the serotonin transporter from zebrafish, Danio rerio, (drSERT) and compared its pharmacological profile to that of the human serotonin transporter (hSERT) with respect to inhibition of [3H]5‐HT uptake and [3H]‐escitalopram binding in transiently transfected human embryonic kidney cells; HEK293‐MSR. Residues responsible for altered affinities inhibitors were pinpointed by generating cross‐species chimeras and subsequent point mutations by site directed mutagenesis. drSERT has a higher affinity towards compounds of the imipramine class, desipramine in particular, exhibiting a 35‐fold increased affinity compared to hSERT. drSERT has a 15–30‐fold lower affinity towards cocaine and cocaine analogues. The differences in ligand recognition are shown to be primarily caused by interspecies differences in TM10 and were tracked down to three residues (Ala505, Leu506 and Ile507).
Group III metabotropic glutamate receptor activation suppresses self‐replication of undifferentiated neocortical progenitor cells
Authors: Nakamichi Noritaka , Yoshida Kohei , Ishioka Yukichi , Makanga Juliet O. , Fukui Masaki , Yoneyama Masanori , Kitayama Tomoya , Nakamura Nobuhiro , Taniura Hideo , Yoneda Yukio 
Published: February 2008

AbstractWe evaluated the possible functional expression of metabotropic glutamate receptors (mGluRs) by neural progenitors from embryonic mouse neocortex. Constitutive expression was seen with group I, II, and III mGluRs in undifferentiated cells and neurospheres formed by clustered cells during culture with epidermal growth factor. The group III mGluR agonist,l‐2‐amino‐4‐phosphonobutyrate, drastically reduced proliferation activity at 1–100 μM without inducing cell death, with group I and group II mGluR agonists being ineffective, in these neurospheres. Both forskolin and a group III mGluR antagonist significantly increased the proliferation alone, but significantly prevented the suppression byl‐2‐amino‐4‐phosphonobutyrate. Activation of group III mGluR significantly decreased mRNA expression of the cell cycle regulator cyclinD1, in addition to inhibiting the transactivation mediated by cAMP of cyclinD1 gene in the pluripotent P19 progenitor cells. Prior activation of group III mGluR led to a significant decrease in the number of cells immunoreactive for a neuronal marker, with an increase in that for an astroglial marker irrespective of differentiation inducers. These results suggest that group III mGluR may be functionally expressed to suppress self‐renewal capacity through a mechanism related to cAMP formation with promotion of subsequent differentiation into astroglial lineage in neural progenitors.