bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complete androgen insensitivity without Wolffian duct development: the AR‐A form of the androgen receptor is not sufficient for male genital development
Authors: Barbaro Michela , Oscarson Mikael , Almskog Ingrid , Hamberg Hans , Wedell Anna 
Published: April 2007

SummaryBackground  The androgen receptor (AR) is essential for the differentiation of male external and internal genitalia. It is normally present in two forms, a full‐length form B and an N‐terminal truncated form A with still unknown function. Mutations in the AR gene cause androgen insensitivity syndrome (AIS), which is divided into subgroups according to the degree of undermasculinization. Patients with completely female external genitalia are classified as complete AIS (CAIS). However, a recent study has shown that some CAIS patients have signs of internal male genital differentiation due to missense mutations that show some degree of residual function.Objective  We aimed to study the expression of the different forms of the AR in two CAIS patients in relation to the development of male internal genital structures. One patient had a mutation (L7fsX33) that affects only the full‐length AR‐B form of the AR, whereas the other had a nonsense mutation (Q733X) affecting both isoforms.Measurements and results  We thoroughly analysed internal genitalia at surgery and by histological examination. No signs of Wolffian duct (WD) development were present in any of the patients. Western blotting of proteins from gonadal and genital skin fibroblasts was performed with AR antibodies directed against different AR epitopes. The N‐terminally truncated A form was expressed in normal amounts in the patient with the L7fsX33 mutation while no AR was detected in the other patient.Conclusion  The presence of the AR‐A form does not seem to be sufficient for WD maintenance and differentiation.
The impact of a TSH receptor gene polymorphism on thyroid‐related phenotypes in a healthy Danish twin population
Authors: Hansen Pia Skov , Van Der Deure Wendy M. , Peeters Robin P. , Iachine Ivan , Fenger Mogens , Sørensen Thorkild I. A. , Kyvik Kirsten O. , Visser Theo J. , Hegedüs Laszlo 
Published: April 2007

SummaryObjectives The Asp727Glu polymorphism in the TSH receptor (TSHR) gene is associated with serum TSH levels. However, the proportion of genetic variation accounted for by this polymorphism is unknown. In this study, we (1) examined the association of the Asp727Glu polymorphism with thyroid size, serum levels of TSH, thyroid hormones, and thyroid antibodies in 1241 healthy Danish twin individuals and (2) assessed the contribution of the polymorphism to the trait variation and the genetic variance.Measurements The effect of the genotype on the traits (mean ± SD) was established; associations between the TSHR‐Asp727Glu polymorphism and measures of thyroid homeostasis were assessed and the effect of the polymorphism on the trait's phenotypic variability was quantified by incorporating the genotype information in structural equation modelling.Results The genotype distribution was Asp/Asp 84·9%; Asp/Glu 14·5% and Glu/Glu 0·6%. Carriers of the TSHR‐Glu727 allele had lower TSH levels (noncarriersvs.carriers: 1·78 ± 0·93vs.1·60 ± 0·84 mU/l,P = 0·04). Regression analysis showed an association between the TSHR‐Asp727Glu polymorphism and serum TSH (P = 0·007). The polymorphism accounted for 0·91% of the total phenotypic variance in serum TSH levels. Including the genotype in quantitative genetic modelling improved the model fit (P = 0·001); however, the genetic influence on serum TSH not attributable to this specific genetic variant was only reduced from 68·2% to 67·8%. The polymorphism was not significantly associated with thyroid size, thyroid hormones or thyroid antibody levels.Conclusions The TSHR‐727Glu allele was associated with decreasing TSH levels; however, the contribution to the genetic variance was very small. No association was found with other thyroid‐related measures.
Quality of life and psychiatric sequelae following aneurysmal subarachnoid haemorrhage: does neuroendocrine dysfunction play a role?
Authors: Kreitschmann‐Andermahr Ilonka , Poll Eva , Hutter Bernd O. , Reineke Andrea , Kristes Sabine , Gilsbach Joachim M. , Saller Bernhard 
Published: April 2007

SummaryObjective  Patients who have sustained aneurysmal subarachnoid haemorrhage (SAH) often suffer persistent impairments in their quality of life (QoL) and psychological disturbances despite a good neurological outcome. In the light of the high prevalence of partial hypopituitarism in SAH survivors demonstrated in recent investigations, we aimed to determine whether neuroendocrine dysfunction has an impact on QoL and neurobehavioural symptoms in these patients.Design/patients  QoL, depression and psychological distress were assessed in 40 SAH survivors who had undergone endocrine function testing at least 1 year after the haemorrhage.Measurements  QoL was assessed using the Nottingham Health Profile (NHP), the Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL‐AGHDA) and the Short Form‐36 questionnaire (SF‐36). The Beck Depression Inventory (BDI) and the Impact of Event Scale (IES) were used to evaluate depression and symptoms of current subjective distress in response to the SAH as a stressful life event, respectively.Results  In a stepwise multiple regression analysis, basal cortisol level was included as the first and often only predictor for several QoL domains assessing psychological aspects of well‐being and depression whereas physical aspects of QoL were predicted primarily by neurological recovery from the SAH. Severe GH deficiency (GHD) was the first predictor for the criterion NHP subscale ‘Energy’ and highest stimulated ACTH level in the insulin tolerance test (ITT) was the first predictor for disturbed sleep as assessed with the NHP subscale ‘Sleep’.Conclusion  Our results provide preliminary data that neuroendocrine disturbances contribute to disturbed QoL, depression and sleeping disturbances in SAH patients.
Mixed lineage kinases (MLKs): a role in dendritic cells, inflammation and immunity?
Authors: Handley Matthew E. , Rasaiyaah Jane , Chain Benjamin M. , Katz David R. 
Published: April 2007

SummaryThis review summarizes current knowledge about the mixed lineage kinases (MLKs) and explores their potential role in inflammation and immunity. MLKs were identified initially as signalling molecules in the nervous system. They were also shown to play a role in the cell cycle. Further studies documented three groups of MLKs, and showed that they may be activated via the c‐Jun NH2terminal kinase (JNK) pathway, and by Rho GTPases. The biochemistry of the MLKs has been investigated in considerable detail. Homodimerization and heterodimerization can occur, and both autophosphorylation and autoinhibition are seen. The interaction between MLKs and JNK interacting protein (JIP) scaffolds, and the resultant effects on mitogen activated protein kinases, have been identified. Clearly, there is some redundancy within the MLK pathway(s), since mice which lack the MLK3 molecule are not abnormal. However, using a combination of biochemical analysis and pharmacological inhibitors, several recent studiesin vitrohave suggested that MLKs are not only expressed in cells of the immune system (as well as in the nervous system), but also may be implicated selectively in the signalling pathway that follows on toll‐like receptor ligation in innate sentinel cells, such as the dendritic cell.
Interleukin‐1α and tumour necrosis factor‐α modulate the production of monocyte chemoattractant protein‐1 by cultured human glomerular visceral epithelial cells
Authors: PRODJOSUDJADI Wiguno , VAN DET Nicole F , VERHAGEN Nicole AM , GERRITSMA Jort SJ , BRUIJN Jan A , DAHA Mohamed R , VAN ES Leendert A 
Published: April 2007

Summary: Mediators released by glomerular macrophages may stimulate glomerular visceral epithelial cells (GVEC) to produce cytokines, growth factors or extracellular matrix components. This study describes that human GVEC produce monocyte chemoattractant protein‐1 (MCP‐1), a monocyte‐specific chemotactic factor, and the effects of interleukin‐lα (IL‐1α) and tumour necrosis factor‐α (TNF‐a) on the production of MCP‐1 by GVEC.We observed that the intensity of MCP‐1 staining in GVEC is stronger in membranous nephropathy and glomerulosclerosis than in normal kidneys. Various cell lines of GVEC produced significant amounts of MCP‐1, as assessed by inhibition radio‐immunoassay. the presence of IL‐1α and TNF‐α during culture of GVEC enhanced the production of MCP‐1 in a dose‐ and time‐dependent manner. Glomerular visceral epithelial cells in culture express mRNA for MCP‐1 and the expression is upregulated 2.0‐ and 1.4‐fold in the presence of optimal concentration of IL‐1α and TNF‐α, respectively. De novo synthesis of MCP‐1 is supported by the observation that MCP‐1 production is fully inhibited by cydoheximide. Monocyte chemoattractant protein‐1 isolated from GVEC supernatants exhibits a molecular size of 12 and 10 kDa as determined by gel filtration chromatography. Both sizes of MCP‐1 is chemotactically active for monocytes.This study shows increased MCP‐1 production by cultured human GVEC after stimulation with the inflammatory cytokines IL‐1α and TNF‐α. the expression of MCP‐1 in GVEC was found to be upregulated in membranous nephropathy and glomerulosclerosis. These findings suggest that MCP‐1 may be involved in glomerular injury in these diseases. the possible role of MCP‐1 in the pathogenesis of human glomerulonephritis is discussed.
HVC interneurons are not renewed in adult male zebra finches
Authors: Scotto‐Lomassese Sophie , Rochefort Christelle , Nshdejan Arpenik , Scharff Constance 
Published: April 2007

AbstractAdult neurogenesis is a widespread phenomenon in many species, from invertebrates to humans. In songbirds, the telencephalic region, high vocal center (HVC), continuously integrates new neurons in adulthood. This nucleus consists of a heterogenous population of inhibitory interneurons (HVCIN) and two populations of projection neurons that send axons towards either the robust nucleus of the arcopallium (HVCRA) or the striatal nucleus area X (HVCX). New HVC neurons were initially inferred to be interneurons, because they lacked retrograde labelling from the HVC's targets. Later studies using different tracers demonstrated that HVCRA are replaced but HVCX are not. Whether interneurons are also renewed became an open question. As the HVC's neuronal populations display different physiological properties and functions, we asked whether adult HVC indeed recruits two neuronal populations or whether only the HVCRA undergo renewal in adult male zebra finches. We show that one month after being born in the lateral ventricle, 42% of the newborn HVC neurons were retrogradely labelled by tracer injections into the RA. However, the remaining 58% were not immunoreactive for the neurotransmitter GABA, nor for the calcium‐binding proteins, parvalbumin (PA), calbindin (CB) and calretinin (CR) that characterize different classes of HVCIN. We further established that simultaneous application of parvalbumin, calbindin and calretinin antibodies to HVC revealed approximately the same fraction of HVC neurons, i.e. 10%, as could be detected by GABA immunoreactivity. This implies that the sum of HVCIN expressing the different calcium‐binding proteins constitute all inhibitory HVCIN. Together these results strongly suggest that only HVCRA are recruited into the adult HVC.
Endocannabinoids mediate muscarine‐induced synaptic depression at the vertebrate neuromuscular junction
Authors: Newman Zachary , Malik Priya , Wu Tse‐Yu , Ochoa Christopher , Watsa Nayantara , Lindgren Clark 
Published: April 2007

AbstractEndocannabinoids (eCBs) inhibit neurotransmitter release throughout the central nervous system. Using theCeratomandibularismuscle from the lizardAnolis carolinensiswe asked whether eCBs play a similar role at the vertebrate neuromuscular junction. We report here that the CB1cannabinoid receptor is concentrated on motor terminals and that eCBs mediate the inhibition of neurotransmitter release induced by the activation of M3muscarinic acetylcholine (ACh) receptors.N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide, a CB1antagonist, prevents muscarine from inhibiting release and arachidonylcyclopropylamide (ACPA), a CB1receptor agonist, mimics M3activation and occludes the effect of muscarine. As for its mechanism of action, ACPA reduces the action‐potential‐evoked calcium transient in the nerve terminal and this decrease is more than sufficient to account for the observed inhibition of neurotransmitter release. Similar to muscarine, the inhibition of synaptic transmission by ACPA requires nitric oxide, acting via the synthesis of cGMP and the activation of cGMP‐dependent protein kinase. 2‐Arachidonoylglycerol (2‐AG) is responsible for the majority of the effects of eCB as inhibitors of phospholipase C and diacylglycerol lipase, two enzymes responsible for synthesis of 2‐AG, significantly limit muscarine‐induced inhibition of neurotransmitter release. Lastly, the injection of (5Z,8Z,11Z,14Z)‐N‐(4‐hydroxy‐2‐methylphenyl)‐5,8,11,14‐eicosatetraenamide (an inhibitor of eCB transport) into the muscle prevents muscarine, but not ACPA, from inhibiting ACh release. These results collectively lead to a model of the vertebrate neuromuscular junction whereby 2‐AG mediates the muscarine‐induced inhibition of ACh release. To demonstrate the physiological relevance of this model we show that the CB1antagonistN‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide prevents synaptic inhibition induced by 20 min of 1‐Hz stimulation.
Facilitation of spontaneous glycine release by anoxia potentiates NMDA receptor current in the hypoglossal motor neurons of the rat
Authors: Kono Yu , Shigetomi Eiji , Inoue Kiyoharu , Kato Fusao 
Published: April 2007

AbstractDeficiency in energy supply, such as occurs during hypoxia, anoxia, metabolic stress and mitochondrial failure, strongly affects the excitability of central neurons. Such lowered energy supply evokes various changes in spontaneous synaptic input to the hippocampal and cortical neurons. However, how this energy deprivation affects synaptic input to motor neurons, which are also vulnerable to energy deprivation, has never been addressed. Here we report for the first time the effect of metabolic stress on synaptic input to motor neurons by recording postsynaptic currents in the hypoglossal nucleus. Chemical anoxia with NaCN (1 mm) and anoxia with 95% N2 induced a persistent inward current and a marked and robust increase in action potential‐independent synaptic input. This increase was abolished by strychnine, but not by picrotoxin, CNQX or MK‐801, indicating glycine release facilitation. Blockade of voltage‐dependent Ca2+ channels and extracellular Ca2+ deprivation strongly attenuated this facilitation. The amplitude of inward currents evoked by local application of NMDA to the motor neurons in the presence of strychnine was significantly increased during NaCN application. A saturating concentration of d‐serine occluded this potentiation, suggesting that released glycine activated the glycine‐binding sites of NMDA receptors. By contrast, neurons in the dorsal motor nucleus of the vagus showed no detectable change in synaptic input in response to NaCN. These data suggest that increase in synaptically released glycine in response to metabolic stress may play an exacerbating role in NMDA receptor‐mediated excitotoxicity in motor neurons.
Chronic cocaine sensitizes striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptors
Authors: Centonze Diego , Rossi Silvia , De Chiara Valentina , Prosperetti Chiara , Battista Natalia , Bernardi Giorgio , Mercuri Nicola B. , Usiello Alessandro , Maccarrone Mauro 
Published: April 2007

AbstractBehavioural studies indicate that cannabinoid receptors are implicated in cocaine addiction. The synaptic underpinning of cocaine–cannabinoid receptor interaction is however, obscure. We have studied electrophysiologically the sensitivity of cannabinoid receptors modulating synaptic transmission in the striatum of rats exposed to cocaine. One‐day treatment with cocaine did not modify the synaptic response to HU210, a cannabinoid CB1 receptor agonist. Seven days cocaine‐treatment, conversely, caused conditioned place preference, and sensitized striatal GABAergic synapses to the presynaptic effect of cannabinoid CB1 receptor stimulation. The cannabinoid receptor‐induced modulation of glutamate transmission was unaltered by cocaine. Furthermore, the effects of chronic cocaine on cannabinoid‐mediated regulation of striatal GABA synapses were attenuated one week after the discontinuation of cocaine, and absent two weeks later, indicating the progressive reversibility of the adaptations of cannabinoid system during abstinence of drug consumption. Our data support the concept that modulation of cannabinoid receptors might be useful against drug abuse.
Signalling pathways underlying neural cell adhesion molecule‐mediated survival of dopaminergic neurons
Authors: Ditlevsen Dorte Kornerup , Berezin Vladimir , Bock Elisabeth 
Published: April 2007

AbstractStimulation of the neural cell adhesion molecule (NCAM) by homophilic interactions is known to lead to neurite outgrowth as well as to neuronal survival. Whereas a complex network of signalling molecules is known to be of importance to NCAM‐mediated neurite extension, only limited information is available regarding signalling underlying NCAM‐mediated neuroprotection. Here, we present data suggesting a difference in the signalling events required for survival of rat dopaminergic neurons as compared with neurite outgrowth from the same cell type. Whereas Fyn, fibroblast growth factor receptor, mitogen‐activated protein and ERK kinase, protein kinase A and protein kinase C are required for both responses to NCAM‐induced signalling, phospholipase C and Ca2+‐calmodulin‐dependent kinase II are only necessary for the neurite outgrowth response, but dispensable for neuroprotection.
Neural adaptation reveals state‐dependent effects of transcranial magnetic stimulation
Authors: Silvanto Juha , Muggleton Neil G. , Cowey Alan , Walsh Vincent 
Published: April 2007

AbstractTranscranial magnetic stimulation (TMS) is now widely used as a ‘virtual’ lesion paradigm to investigate behavioural functions, but the mechanisms through which it influences neural processing are unclear. To understand the differential effects of TMS on spatially overlapping populations of neurons we manipulated the relative activity levels of visual neurons by adapting subjects to a range of visual stimuli. By applying TMS to the visual cortex representing the central visual field we have shown in two experiments that the behavioural and perceptual effects of TMS depend on the state of adaptation of the neural population stimulated by TMS. Specifically, we have demonstrated that within the stimulated area TMS perceptually facilitates the attributes encoded by the less active neural population. We have demonstrated the generality of this principle for both suprathreshold and subthreshold TMS as well as for colour and orientation‐contingent colour using both subjective reports and psychophsyical measures. These findings can explain how TMS disrupts cognitive functions and therefore have implications for all studies which use TMS to disrupt behaviour.
Local Government Finance: Assessing the Central Governmant's Contribution
Authors: CRISPIN A. 
Published: April 2007

SUMMARYIt is widely believed that between 60 to 66 per cent. of local authority expenditure (or income) is met by grants from central government alone. This popularly held view is challenged in this paper through a consideration of the current system of funding. We begin with the rate support grant procedure and identify some common sources of misunderstanding; these concern the definition of the rate support grant itself and the true nature of relevant expenditure. This leads us to examine the question of local authority miscellaneous income from fees, sales, rents and other sources from which we conclude that its contribution is underestimated. However it is general knowledge that besides miscellaneous income local authorities derive their income from two other principal sources namely, government grants and local rates. Accordingly the remainder of the paper examines in turn the contribution of these three sources towards (i) local authority revenue expenditure in respect of rate fund services, (ii) local authority revenue income and (iii) local authority income including both revenue and capital receipts. In no instance does central government's share approach 60 per cent. Thus, it would appear that the contribution of government is being overestimated while that of miscellaneous income underestimated. The implications of this are discussed.
PUBLIC EXPENDITURE AND POLICY IMPLEMENTATION: THE CASE OF COMMUNITY CARE
Authors: WEBB ADRIAN , WISTOW GERALD 
Published: April 2007

This article explores the contention that the conventions of public expenditure accounting conceal, rather than reveal, the real nature and implications of resource trends. A benchmark — a constant level of service output — is established as a basis for examining the relationship between trends in expenditure inputs and service outputs. Changes in unit costs are identified as the major source of deviation between expenditure and output trends. The impact of resource constraint on policy and policy‐implementation is then examined in relation to one, essentially stable, area of policy in the personal social services: community care.The meaning of the term‘policy’ is far from straightforward and community care is best understood as the interaction of relatively independent streams of policy, towards service outputs and resource inputs, extant in both central and local government. Mechanisms by which policy streams could be reconciled are of particular interest and an innovative example — joint finance — is examined in some detail.
TAKING STOCK OF THE LOCAL AUTHORITY ASSOCIATIONS
Authors: ISAAC‐HENRY K. 
Published: April 2007

This article examines the achievements of the local authority associations in the period from 1974 to the present. In particular, it considers whether the associations have met the major objectives set by their predecessors. The conclusion indicates that there are a number of factors which have inhibited the achievement of these objectives.Two of the main inhibiting factors are the close connection between the associations and central government, and their readiness to respond to every move the centre makes. The associations might now consider adopting a weaker connection and a more discriminating response in relation to central government.
WOMEN AS ‘ANOMALIES’: THE ANOMALIES REGULATIONS OF 1931, THEIR BACKGROUND AND IMPLICATIONS
Authors: TOMLINSON J. D. 
Published: April 2007

In 1931, the fraught government discussion over the unemployment insurance scheme resulted in the introduction of a set of Anomalies Regulations which greatly restricted the nights of certain categories of workers to claim unemployment benefit. The group most affected by these Regulations were married women, 320000 of whom had been downed benefit under these Regulations by the end of 1936, out of a total of 650 000 insured married women.Recently (Benjamin and Kochin 1979) this measure has been cited in the revived arguments about the effects of unemployment benefit on the level of unemployment. Important as this issue is, the Anomalies Regulations are also of much broader interest in that they open up the whole question of the place of women in the unemployment insurance system.This article is divided into four sections. The first outlines the position of women in the unemployment insurance system prior to 1931. The second looks at the immediate circumstances of the Regulations enactment. The third looks at their immediate consequences. The fourth looks more broadly at the problems of women and the unemployment insurance system.