bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of AMPA currents by D2 dopamine receptors in striatal medium‐sized spiny neurons: are dendrites necessary?
Authors: Hernández‐Echeagaray Elizabeth , Starling Amaal J. , Cepeda Carlos , Levine Michael S. 
Published: April 2004

AbstractGlutamatergic afferents from the neocortex constitute the major excitatory input to striatal medium‐sized spiny neurons (MSNs). Glutamate's actions on MSNs are modulated by dopamine (DA) through D1 and D2 receptor families. Although D1 modulation of glutamate responses has been well‐characterized, the contribution of postsynaptic D2 receptors to α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) responses has not been studied extensively. We examined DA modulation of AMPA currents using whole‐cell voltage‐clamp recordings of MSNs acutely dissociated and in slices. In dissociated cells, the D2 agonist quinpirole (10 µm) produced small and inconsistent effects on AMPA currents. The magnitude of the current, as well as its modulation by quinpirole, was related to the dendritic elaboration of the dissociated cell. Thus, quinpirole altered AMPA currents only slightly when few initial dendritic segments were present. The amplitude of the current was greater and quinpirole consistently decreased this current in dissociated cells displaying at least three primary dendrites and several secondary and tertiary dendrites. Cyclothiazide, a compound that prevents AMPA receptor desensitization, greatly increased AMPA currents. In the presence of cyclothiazide, quinpirole also consistently reduced AMPA currents. Finally, in slices, AMPA current amplitude was always reduced after application of quinpirole. Sulpiride, a D2 antagonist, prevented attenuation of AMPA currents in both acutely dissociated neurons and neurons in slices. These results provide evidence that AMPA currents are attenuated by DA via activation of postsynaptic D2 receptors. In addition, they indicate that the dendrites and/or the amplitude of the current are important variables for DA modulation of AMPA currents in MSNs.
AMPA receptor‐mediated presynaptic inhibition at cerebellar GABAergic synapses: a characterization of molecular mechanisms
Authors: Satake Shin'Ichiro , Saitow Fumihito , Rusakov Dmitri , Konishi Shiro 
Published: April 2004

AbstractA major subtype of glutamate receptors, AMPA receptors (AMPARs), are generally thought to mediate excitation at mammalian central synapses via the ionotropic action of ligand‐gated channel opening. It has recently emerged, however, that synaptic activation of AMPARs by glutamate released from the climbing fibre input elicits not only postsynaptic excitation but also presynaptic inhibition of GABAergic transmission onto Purkinje cells in the cerebellar cortex. Although presynaptic inhibition is critical for information processing at central synapses, the molecular mechanisms by which AMPARs take part in such actions are not known. This study therefore aimed at further examining the properties of AMPAR‐mediated presynaptic inhibition at GABAergic synapses in the rat cerebellum. Our data provide evidence that the climbing fibre‐induced inhibition of GABA release from interneurons depends on AMPAR‐mediated activation of GTP‐binding proteins coupled with down‐regulation of presynaptic voltage‐dependent Ca2+ channels. A Gi/o‐protein inhibitor, N‐ethylmaleimide, selectively abolished the AMPAR‐mediated presynaptic inhibition at cerebellar GABAergic synapses but did not affect AMPAR‐mediated excitatory actions on Purkinje cells. Furthermore, both Gi/o‐coupled receptor agonists, baclofen and DCG‐IV, and the P/Q‐type calcium channel blocker ω‐agatoxin IVA markedly occluded the AMPAR‐mediated inhibition of GABAergic transmission. Conversely, AMPAR activation inhibited action potential‐triggered Ca2+ influx into individual axonal boutons of cerebellar GABAergic interneurons. By suppressing the inhibitory inputs to Purkinje cells, the AMPAR‐mediated presynaptic inhibition could thus provide a feed‐forward mechanism for the information flow from the cerebellar cortex.
Genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection*
Authors: Hellberg Å. , Ringressi A. , Yahalom V. , Säfwenberg J. , Reid M. E. , Olsson M. L. 
Published: April 2004

SummaryThe aim of this study was to further explore the molecular genetic bases of the clinically important but rare blood group phenotypes p, P1k and P2k by analysis of the 4‐α‐galactosyltransferase (Pk) and 3‐β‐N‐acetylgalactosaminyltransferase (P) genes responsible for synthesis of the related Pk (Gb3) and P (Gb4) antigens respectively. Lack of these glycolipid moieties is associated with severe transfusion reactions and recurrent spontaneous abortions but also offers immunity against certain infectious agents. Blood samples from 20 p and 11 P1k or P2k individuals of different geographic and ethnic origin were investigated. DNA sequencing by capillary electrophoresis was performed following amplification of the coding regions in the Pk or P genes. In the Pk gene, nine novel and five previously described mutations were detected. One of the newly found mutations introduced an immediate stop, five shifted the reading frame introducing premature stop codons and three were missense mutations causing amino acid substitutions in conserved regions of the transferase. Four new and two previously described mutations in the P gene were found. Three of the novel alleles reported here carried nonsense mutations whilst the fourth allele had a missense mutation. The finding of 13 novel mutations in 14 alleles emphasizes further the genetic heterogeneity at the glycosyltransferase loci underlying the GLOB blood group system and collection.
FLT‐3 aberrations in acute promyelocytic leukaemia: clinicopathological associations and prognostic impact
Authors: Au Wing Y. , Fung Alvin , Chim Chor S. , Lie Albert K. , Liang Raymond , Ma Edmond S. K. , Chan Cheuk H. , Wong Kit F. , Kwong Yok L. 
Published: April 2004

Summary FLT‐3 aberrations that occur as an internal tandem duplication (ITD) or a mutation at the activation‐loop position 835, D835, are common in acute promyelocytic leukaemia (APL). We investigated the clinicopathological associations and prognostic impact of FLT‐3 aberrations in a cohort of APL patients. FLT‐3 exons 11 and 12 were amplified by polymerase chain reaction (PCR), and the ITD was recognized as an increase in the size of the PCR product. FLT‐3 exon 17 was amplified, and D835 mutation was identified by loss of an EcoRV site, followed by DNA sequencing. Of 82 patients studied, FLT‐3 aberrations were detected in 35 cases (43%) at diagnosis (ITD: 16; D835 mutation: 18; ITD + D835 mutation: 1). FLT‐3 ITD, but not D835 mutations, was significantly associated with higher presentation white blood cell count (WBC) and microgranular morphology. Early/induction deaths were related to male sex and high presentation WBC. There was a trend for FLT‐3 ITD to be associated with non‐remission (P = 0·06). For disease‐free survival, high WBC was the only significant adverse factor. Male sex, high WBC and FLT‐3 ITD were significant adverse factors for overall survival. These findings have important implications on the possible use of FLT‐3 inhibitors in the treatment of APL.
Prophylactic effect of recombinant factor VIIa in factor VII deficient patients
Authors: Mathijssen Natascha C. J. , Masereeuw Rosalinde , Verbeek Kitty , Maurice Lavergne J. , Costa Jean‐Marc , Van Heerde Waander L. , Nováková Irena R. O. 
Published: April 2004

SummaryInherited factor VII (FVII) deficiency is a rare autosomal recessive disorder associated with a bleeding tendency. We describe three patients with congenital FVII deficiency who have been treated with activated recombinant factor VII (rVIIa). Two patients had novel mutations and were treated prophylactically with 1·2 mg rVIIa two to three times a week. Patients 1 and 2 had a severe bleeding tendency. The frequency and severity of bleeding decreased by treatment with rVIIa compared with similar treatment with plasma‐derived FVII. The third patient with a moderate bleeding phenotype was treated on demand and showed no change in the frequency of bleeding upon treatment with rVIIa or plasma products. The beneficial effect of rVIIa cannot be explained by the rVIIa half‐lives. Pharmacokinetical analysis showed rVIIa activity half‐lives of 35, 50 and 54 min for patients 1, 2 and 3, respectively. In conclusion, prophylactic treatment of FVII deficient patients with rVIIa appears to be applicable, safe and successful, although the mechanism of action remains to be elucidated.
Urocortin III, A Brain Neuropeptide of the Corticotropin‐Releasing Hormone Family: Modulation by Stress and Attenuation of Some Anxiety‐Like Behaviours
Authors: Venihaki M. , Sakihara S. , Subramanian S. , Dikkes P. , Weninger S. C. , Liapakis G. , Graf T. , Majzoub J. A. 
Published: April 2004

AbstractFollowing its discovery 20 years ago, corticotropin‐releasing hormone (CRH) has been postulated to mediate both hormonal and behavioural responses to stressors. Here, we characterize and describe a behavioural role for the murine gene, UcnIII, which encodes a recently discovered CRH‐related neuropeptide, urocortin III. We found that mouse UcnIII is expressed predominantly in regions of the brain known to be involved in stress‐related behaviours, and its expression in the hypothalamus increases following restraint. In addition, we found that intracerebroventricular administration of mUcnIII stimulates behaviours that are associated with reduced anxiety, including exploration of an open field and decreased latency to enter the lit compartment of a dark‐light chamber, but has no effect on the elevated‐plus maze. Finally, we found that mUcnIII does not exert any effects on the hormonal stress response. Based upon our findings, UcnIII may be an endogenous brain neuropeptide that is modulated by stress and stimulates behaviours associated with reduced anxiety. In this capacity, UcnIII may attenuate stress‐related behaviours, which may be useful both to help cope with stressful situations as well as to avoid pathology associated with excessive reaction to stressors.
Modulation of Oestrogen Receptor‐β mRNA Expression in Rat Paraventricular and Supraoptic Nucleus Neurones Following Adrenal Steroid Manipulation and Hyperosmotic Stimulation
Authors: Somponpun S. J. , Holmes M. C. , Seckl J. R. , Russell J. A. 
Published: April 2004

AbstractMagnocellular neurosecretory neurones in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei express oestrogen receptor β (ERβ) but not ERα. In the PVN, ERβ is strongly expressed in the ventromedial parvocellular neurones projecting to the brainstem. We used quantitative in situ hybridization, with 35S‐labelled riboprobes, to study heterologous regulation by manipulating adrenal steroid hormones (72 h after adrenalectomy ± corticosterone replacement; repeated stress: halothane inhalation, environmental cold, immobilization, each daily for 3 days) in male rats. Adrenalectomy increased ERβ mRNA expression in the magnocellular PVN and SON, by 2.2 and 2.5‐fold, respectively, with no effect in the ventromedial parvocellular PVN neurones. Corticosterone replacement partially prevented the increases in ERβ mRNA expression in magnocellular PVN and SON neurones. Repeated stress over 72 h had no effect on ERβ mRNA expression in the magnocellular PVN or SON, but increased expression 1.4‐fold in the ventromedial parvocellular PVN neurones. Although consequences of hydromineral balance derangement after adrenalectomy may stimulate magnocellular neurones, strongly stimulating the neurones by giving intact male rats 2% saline to drink for 72 h decreased ERβ mRNA expression in the magnocellular PVN and SON neurones by approximately 60%, and in the ventromedial parvocellular PVN neurones by 13%. Thus, ERβ mRNA expression is negatively regulated by basal glucocorticoid secretion in magnocellular PVN and SON neurones, and positively regulated by stress in ventromedial parvocellular PVN neurones. However, ERβ mRNA expression in magnocellular neurones is negatively linked to hyperosmotic stimulation of the neurones. The 6.25‐fold variation in ERβ mRNA expression in magnocellular neurones from salt‐loading to adrenalectomy could alter their sensitivity to oestrogens. Consequently, regulation of oxytocin and vasopressin neurone activity via ERβ is expected to vary according to their functional state and, in particular, on basal glucocorticoid actions.
Prevention of hepatitis C virus infection*
Authors: Kew M. , François G. , Lavanchy D. , Margolis H. , Van Damme P. , Grob P. , Hallauer J. , Shouval D. , Leroux‐Roels G. , Meheus A. 
Published: April 2004

Summary.In spite of advances made in our understanding of the biology of the hepatitis C virus (HCV), the epidemiology and natural history of HCV infection, and the treatment of chronic hepatitis C, the development and worldwide implementation of a comprehensive prevention and control strategy remains necessary. A World Health Organization informal consultation with the Viral Hepatitis Prevention Board was convened and met in Geneva, Switzerland, 13–14 May 2002, to review epidemiological and public health aspects of HCV infection, and the various prevention and control strategies that are currently in place. Based on the presentations and discussions, a number of specific recommendations were made, which should be considered in conjunction with previously published recommendations.
Why is psoriasis uncommon in Africans? The influence of dietary factors on the expression of psoriasis
Authors: Namazi M. R. 
Published: April 2004

AbstractPsoriasis is uncommonly seen in Africans, probably partly due to genetic factors. However, the dietary habits of Africans may provide another explanation, which is explored in this paper. Maize, the staple diet in most parts of Africa, is high in linoleic acid but low in other polyunstaturated fatty acids and riboflavin. Linoleic acid is a precursor of prostaglandin E2 (PGE2) and its high intake, especially in the absence of other polyunsaturated fatty acids (PUFAs) and riboflavin, results in high tissue production of PGE2. PGE2 is known to suppress cellular immunity, resulting in decreased expression of psoriasis.
Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study
Authors: Adler Caleb M , Holland Scott K , Schmithorst Vince , Wilke Marko , Weiss Kenneth L , Pan Hai , Strakowski Stephen M 
Published: April 2004

Objectives:  Prefrontal white matter has been hypothesized to be integral to the pathophysiology of bipolar disorder. Recent morphometric studies however, have not observed changes in white matter in bipolar patients. We hypothesized that changes in prefrontal function in bipolar disorder, widely reported in the literature, may be related to a loss of white matter tract integrity with a resultant dysconnectivity syndrome. In this study we utilized diffusion tensor imaging (DTI) to examine prefrontal white matter in patients with bipolar disorder.Methods:  Nine patients with bipolar disorder and nine healthy controls were recruited. DTI and localizing anatomic data were acquired, and regions of interest (ROIs) identified in the prefrontal white matter at 15, 20, 25, and 30 mm superior to the anterior commissure (AC). Fractional anisotropy (FA) and trace apparent diffusion coefficient (TADC) were compared by ROI between study groups.Results:  The FA of ROIs 25 and 30 mm above the AC was significantly reduced in patients with bipolar disorder; FA of all ROIs showed high‐medium to large effect sizes. No significant group differences were identified in TADC.Conclusions:  Our findings suggest that a loss of bundle coherence is present in prefrontal white matter. This loss of coherence may contribute to prefrontal cortical pathology in patients with bipolar disorder.
Menstrually related symptom changes in women with treatment‐responsive bipolar disorder
Authors: Karadag Figen , Akdeniz Fisun , Erten Evrim , Pirildar Sebnem , Yucel Basak , Polat Aslihan , Atmaca Murad 
Published: April 2004

Objective:  In the present study, we aimed to evaluate menstrually related symptom changes in euthymic women with treatment‐responsive bipolar disorder (BD) compared with healthy control subjects and investigate the presence of premenstrual dysphoric disorder (PMDD).Methods:  Thirty‐four euthymic women with treatment‐responsive BD on mood‐stabilizers (lithium and/or valproate) for at least 6 months and 35 control subjects with no history of medical/mental disorder between ages of 18 and 35 years with regular menstrual cycles were prospectively followed up for at least two consecutive menstrual cycles using the Daily Record of Severity of Problems‐Short Form (DRSP). Each subject was administered the retrospective self‐report questionnaire, Premenstrual Assessment Form (PAF), in the first postmenstrual phase of the menstrual cycle. Venous blood samples were collected between 19 and 22 days of menstrual cycle to evaluate ovulation by measuring the serum progesterone levels.Results:  The differences in mean age, age of onset of menses, cycle length and bleeding length did not appear to be significantly meaningful between groups. In the retrospective assessment of premenstrual symptom changes, controls complained more than women with BD. More controls showed a 30% change in DRSP and in depressive and physical sub‐groups than the women with BD. Controls demonstrated a significant increase compared with treatment‐responsive BD patients in total, depressive, anxiety and attention sub‐group scores of DRSP from the postmenstrual to the premenstrual phase, whereas the scores of vegetative symptoms of controls and women with BD did not differ significantly during one cycle or both. Significant menstrual cycle effect was observed in both groups.Conclusion:  Within the limitations of the study, the results suggest that ongoing mood‐stabilizing treatment may have a prophylactic effect against premenstrual symptom changes in women with treatment‐responsive BD.
The Impact of European Works Councils on Management Decision‐Making in UK and US‐based Multinationals: A Case Study Comparison
Authors: Marginson Paul , Hall Mark , Hoffmann Aline , Müller Torsten 
Published: April 2004

AbstractThe operation of European Works Councils (EWCs) is taking management and employee representatives in MNCs into uncharted territory. In particular, for companies headquartered in Anglo‐Saxon economies there is little domestic tradition of statutory employee consultation. Drawing on comparative case studies, this article investigates the impact of EWCs on the process and outcomes of corporate‐level management decision‐making in UK and US‐based MNCs. Variation in EWC impact arises from the interaction of structural factors, such as business focus, management organisation and pre‐existing industrial relations arrangements, and agency factors, including management policy and the cohesion of employee representatives.
Local Participatory Democracy in Britain's Health Service: Innovation or Fragmentation of a Universal Citizenship?
Authors: Milewa Timothy 
Published: April 2004

Abstract A political emphasis upon the devolution of governance and management in the British National Health Service has, since 1997, been paralleled by an apparent concern to reinvigorate patient and public involvement in aspects of planning and decision‐making. A quasi‐communitarian rhetoric and echoes of nineteenth‐century welfare mutualism have accompanied significant reform of arrangements for patient and public involvement. This article considers the degree to which this fusion of normative exhortation and structural reform heralds a marked evolution in the principles and practice of participatory democracy in the planning and governance of health care. The reforms, in historical perspective, appear to constitute a significant extension of the arenas within which citizens can explore and debate issues pertaining to the health service. But selective political recourse to quasi‐communitarian sentiment points to an embryonic policy discourse that links entitlements to obligations on the part of those reliant on the NHS. This may be of considerable significance in a system of health care to which entitlement has, historically, been cast as a right of citizenship.
Lone Parents and Civil Law: Their Experience of Problems and Their Advice‐seeking Behaviour
Authors: Buck Alexy , Pleasence Pascoe , Balmer Nigel , O'Grady Aoife , Genn Hazel 
Published: April 2004

Abstract The percentage of dependent children living in lone‐parent families has more than tripled in Britain over the last 30 years. Though there is much diversity within this lone‐parent population, there are common experiences and characteristics. Lone‐parent families tend to be headed by women, to be poor, on benefits and experience problems with ill health and disability. This paper examines lone parenthood in the context of the experience of justiciable problems (problems for which there is a potential legal remedy), drawing upon a large‐scale survey of 5,611 people representative of the population of England and Wales. The survey included 223 lone parents, who were likely to be female, to be living in rented accommodation, to be on a low income, to be economically inactive and to be in receipt of benefits. Lone parents were significantly more likely than others to have experienced a justiciable problem. Lone parents sought advice for their problems more often than others, particularly from solicitors, even after controlling for problems experienced. Lone parents were more likely than others to receive legal‐aid funding. Lastly, lone parents found trying to resolve problems particularly stressful, though they tended to believe that their life had improved as a consequence of doing so.