bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel function of theC‐terminal lipid moieties of Rab3A small G protein implicated in Ca2+‐dependent exocytosis — inhibition of interaction with GTP and reduction of this inhibition by phospholipid
Authors: Jin‐no Yasunari , Shirataki Hiromichi , Senbonmatsu Takaaki , Yamamoto Tomomi , Fujita Yasuyuki , Nakanishi Hiroyuki , Takai Yoshimi 
Published: December 2004

Background: Rab3A small G protein is implicated in Ca2+‐dependent exocytosis. It undergoes post‐translational lipid‐modifications at its C‐terminal region. These lipid moieties are important for the actions of the regulators of Rab3A, but not for the interaction with its downstream target. Results:We have found another function of the C‐terminal lipid moieties of Rab3A. GTP rapidly associates with the guaninenucleotide‐free form of unmodified Rab3A, but not with the same form of modified Rab3A. Moreover, GTP rapidly dissociates from the GTP‐bound form of modified Rab3A, but not from the same form of unmodified Rab3A. The association of GTP with the guaninenucleotide‐free form of modified Rab3A is stimulated by the Rab3GDP/GTP exchange protein (Rab3 GEP), and the dissociation of GTP from the GTP‐bound form is markedly reduced by synaptic vesiclephospholipid. Conclusions: These results suggest that the interaction of the lipid moieties of Rab3A with Rab3GEP or synaptic vesicles is required for the interaction of modified Rab3A with GTP. Moreover, these results — together with the fact that Rabphilin‐3A associated withsynaptic vesicles inhibits the activity of Rab3GTPase‐activating protein — suggest that the GTP‐bound form of modified Rab3A is associated with synaptic vesicles through both Rabphilin‐3A and the vesicle phospholipid.
Effects of steroids on oxytocin secretion by the human prostate in vitro
Authors: Assinder S. J. , Nicholson H. D. 
Published: December 2004

SummaryOxytocin (OT) concentrations are elevated in prostate tissue of patients with benign prostatic hyperplasia (BPH). Oxytocin specifically increases growth, 5 α‐reductase activity and contractility in the prostate. In the rat prostatic OT concentrations are regulated by gonadal steroids, with androgens reducing but oestrogens increasing OT concentrations. The regulation of prostatic oxytocin in man is not understood. This study investigates the effects of gonadal steroids on oxytocin production by the human prostate. Primary explants (approx. 1 mm3) of prostate tissue from patients with BPH were incubated in Dulbecco's modified Eagle's media in the absence or presence of 10 nmol/L testosterone (T), 10 nmol/L dihydrotestosterone (DHT), T or DHT plus 100 nmol/L of the anti‐androgen cyproterone acetate (CPA), 55 pmol/L diethylstilbestrol (DES), or DES plus DHT. The amount of oxytocin secreted into the media after 3 days was measured by radioimmunoassay. Testosterone and DHT significantly increased oxytocin concentrations secreted into the media from 0.86 ± 0.11 ng/g of tissue (control) to 1.51 ± 0.14 ng/g (p < 0.01) and 1.54 ± 0.13 ng/g (p < 0.05), respectively. Incubation of tissue samples with CPA resulted in oxytocin concentrations similar to control levels. Treatment with DES caused a significant increase from 1.99 ± 0.71 to 3.98 ± 1.36 ng/g (p < 0.05). A similar increase was measured in media of tissue incubated in DES plus DHT (p < 0.001). The results demonstrate that, unlike the rat where androgens decrease oxytocin, in hyperplastic human prostate tissue both androgens and oestrogens increase oxytocin. This imbalance in the regulation of oxytocin may result in promoting prostatic overgrowth in the pathogenesis of BPH.
A kaleidoscope of understandings: spiritual nursing in a multi‐faith society
Authors: MacLaren Jessica 
Published: December 2004

Background.  Spirituality is an increasingly discussed topic in nursing. In some parts of the UK there is a policy requirement to establish policies of spiritual health care which are appropriate to a multi‐cultural society. In the nursing literature, spirituality is discussed from religious and secular perspectives which seem impossible to reconcile into a coherent philosophy.Aims.  To discuss the relationship of spirituality to nursing and to suggest how we can think about spirituality as nurses working in a society of many faiths and cultures.Discussion.  Spirituality can be thought of in relation to individual patients and nurses. It also has significance for the profession of nursing and for health care as a whole. The difficulty of defining spirituality is discussed, and it is suggested that a definition of ‘spiritual nursing’ may be more achievable. Different concepts of spirituality are compared, including religious and secular spirituality. The relationship between religion and spirituality is seen as potentially problematic, with some religions denying the existence of secular spirituality. Secular spirituality and New Age movements are non‐religious but spiritually influential phenomena. The problem for nursing is how to reconcile the immense variety of approaches to spirituality.Conclusions.  The concept of spirituality as a meta‐narrative is considered, and a postmodern appreciation of pluralism is employed as a way of embracing different spiritual realities. Spiritual nursing can be an opportunity for nurses to enlarge their understanding of the human condition rather than a narrowly defined concept to be applied within a model of practice.
Epidermolytic hyperkeratosis: a keratin 1 or 10 mutational event
Authors: Lacz Nicole L. , Schwartz Robert A. , Kihiczak George 
Published: December 2004

AbstractEpidermolytic hyperkeratosis is an unusual type of ichthyosis. This inherited keratinization disorder is characterized clinically by erythema, blistering, and peeling shortly after birth. It may resolve and be replaced with thick scaling. It can lead to life‐threatening complications, such as sepsis. Histologically, there is a hyperkeratosis and vacuolar degeneration. Genetically, this is an autosomal dominant disease with complete penetrance; however, 50% are spontaneous mutations. The clinical phenotype is a result of alterations in the gene(s) for keratin 1 and/or 10. We review this disorder and its therapy, which is mainly symptomatic with emollients and retinoids.
Influencing the national policy process: the role of health consumer groups
Authors: Jones Kathryn , Baggott Rob , Allsop Judith 
Published: December 2004

AbstractIntroduction  Whilst recent research has focused on consumer involvement at local level in the UK, there have been few studies of the representation of user, carer and patients’ interests nationally. This paper concentrates on the role of health consumer groups in representing the collective interests of patients, users and carers in the national policy process.Methods  The research consisted of (a) a semi‐structured postal questionnaire survey of 123 health consumer groups; (b) semi‐structured interviews with key informants from 39 health consumer groups; and (c) semi‐structured interviews with 31 policy actors.Results  Health consumer groups were diverse in their origins, scope and structure, and undertook a wide range of activities relating to policy and service provision. Whilst around half the groups described their primary purpose as service provision, over four‐fifths identified influencing policy at national level as ‘very important’ or ‘important’. Health consumer groups had developed relationships with civil servants, ministers, MPs and peers to widen their policy objectives. Key facilitators in the policy process included experiential knowledge, relationships with policy makers and working in alliances with other health consumer groups or other stakeholders. Key barriers included problems relating to the political agenda, problems with the consultation process, lack of resources and working within a context of unequal power relationships.Conclusion  Health consumer groups are becoming increasingly involved in the health policy process and collectively are becoming an increasingly influential stakeholder. They have a key role to play in ensuring that the patient, user and carer voice is heard in the policy process.
Antagonists for group I mGluRs attenuate excitotoxic neuronal death in cortical cultures
Authors: Strasser Uta , Lobner Doug , Behrens M. Margarita , Canzoniero Lorella M. T. , Choi Dennis W. 
Published: December 2004

AbstractActivation of ion channel‐linked glutamate receptors, especially N‐methyl‐d‐aspartate (NMDA) receptors, mediates the excitotoxic effects of glutamate upon central neurons. We examined the hypothesis that activation of group I metabotropic glutamate receptors (mGluRs) would increase NMDA receptor‐mediated cortical neuronal death. Addition of the selective group I mGluR agonists, dihydroxyphenylglycine (DHPG) or trans‐azetidine‐2,4‐dicarboxylic acid (t‐ADA) potentiated NMDA‐induced neuronal death, and application of the group I mGluR‐selective antagonist, aminoindan‐1,5‐dicarboxylic acid (AIDA), as well as the non‐selective antagonists methyl‐4‐carboxyphenylglycine (MCPG) or 4‐carboxyphenylglycine (4CPG) reduced NMDA‐ and kainate‐induced neuronal death in murine cortical cultures. The pro‐excitotoxic effect of group I mGluR activation may be mediated largely by enhancement of glutamate release, as DHPG potentiated high potassium‐stimulated glutamate release, and the protective effects of both AIDA and MCPG were abolished when NMDA and alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole proprionic acid (AMPA) receptors were blocked immediately after toxic NMDA receptor overstimulation. The present data support the possibility that antagonizing group I mGluRs may be a useful strategy for attenuating excitotoxic neuronal death in certain disease states.
Endogenous ACh enhances striatal NMDA‐responses via M1‐like muscarinic receptors and PKC activation
Authors: Calabresi Paolo , Centonze Diego , Gubellini Paolo , Pisani Antonio , Bernardi Giorgio 
Published: December 2004

AbstractCortical glutamatergic fibres and cholinergic inputs arising from large aspiny interneurons converge on striatal spiny neurons and play a major role in the control of motor activity. We have investigated the interaction between excitatory amino acids and acetylcholine (ACh) on striatal spiny neurons by utilizing intracellular recordings, both in current‐ and in voltage‐clamp mode in rat brain slices. Muscarine (0.3–10 μm) produced a reversible and dose‐dependent increase in the membrane depolarizations/inward currents induced by brief applications of N‐methyl‐d‐aspartate (NMDA), while it did not affect the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)‐induced responses. These concentrations of muscarine did not alter the membrane potential and the current‐voltage relationship of the recorded cells. Neostigmine (0.3–10 μm), an ACh‐esterase inhibitor, mimicked this facilitatory effect. The facilitatory effects of muscarine and neostigmine were antagonized either by scopolamine (3 μm) or by pirenzepine (10–100 nm), an antagonist of M1‐like muscarinic receptors, but not by methoctramine (300 nm), an antagonist of M2‐like muscarinic receptor. Accordingly, these facilitatory effects were mimicked by McN‐A‐343 (1–10 μm), an agonist of M1‐like muscarinic receptors, but not by oxotremorine (300 nm), an agonist of M2‐like receptors. Tetrodotoxin (TTX) did not block the facilitatory effect produced by the activation of muscarinic receptors suggesting that this effect is postsynaptically mediated. The action of neostigmine was prevented either by the intracellular calcium (Ca2+) chelator BAPTA (200 mm) or by preincubating the slices with inhibitors of protein kinase C (PKC) (staurosporine 100 nm or calphostin C 1 μm). McN‐A‐343 did not alter the excitatory post synaptic potentials (EPSPs) evoked by corticostriatal stimulation in the presence of physiological concentration of magnesium (Mg2+ 1.2 mm), while it enhanced the duration of these EPSPs recorded in the absence of external magnesium. Our data show that endogenous striatal ACh exerts a positive modulatory action on NMDA responses via M1‐like muscarinic receptors and PKC activation.
Rhythmic variation in β1‐adrenergic receptor mRNA levels in the rat pineal gland: circadian and developmental regulation
Authors: Pfeffer Martina , Kühn Rebecca , Krug Liselotte , Korf Horst‐Werner , Stehle Jörg H. 
Published: December 2004

AbstractIn the rat pineal gland noradrenaline is released in large quantities from sympathetic nerve endings at the onset of darkness, thereby driving rhythmic melatonin synthesis with elevated levels at night‐time. Upon release, noradrenaline interacts with postsynaptic β1‐adrenergic receptors to activate the cyclic AMP signalling pathway. Well characterized third messengers of this signalling cascade affect cyclic AMP‐inducible genes that are crucially involved in initiation, maintenance and termination of hormone production. Among these third messengers are CREB (cyclic AMP responsive element binding protein) as an activating and ICER (inducible cyclic AMP early repressor) as an inhibitory transcription factor. Because a cyclic AMP‐inducible promoter element is present on the β1‐adrenergic receptor gene, the expression of the receptor itself may be under control of the cyclic AMP‐signalling pathway. By in situ hybridization, Northern blot analysis and RT‐PCR we demonstrate a day/night rhythm in β1‐adrenergic receptor mRNA in the rat pineal gland with elevated levels during the dark period. As this rhythm persists, under constant darkness but is abolished upon removal of the sympathetic innervation, it is truly circadian. A marked day/night difference in the levels of β1‐adrenergic receptor mRNA becomes evident only after postnatal day 10, coinciding with the appearance of a functional cyclic AMP signalling pathway in the rat pineal gland. Furthermore, targeting ICER expression by transfection of pinealocytes with an antisense ICER construct, clearly indicates that the levels of the β1‐adrenergic receptor mRNA are regulated by the cyclic AMP‐signalling pathway in a feedback mechanism.
The neonatal ventral hippocampal lesion model of schizophrenia: effects on dopamine and GABA mRNA markers in the rat midbrain
Authors: Lipska Barbara K. , Lerman Daniel N. , Khaing Zin Z. , Weinberger Daniel R. 
Published: December 2004

AbstractThe neonatal ventral hippocampal lesion in the rat has been used as a model of schizophrenia, a human disorder associated with changes in markers of dopamine and γ‐aminobutyric acid (GABA) circuits in various regions of the brain. We investigated whether alterations in mRNA markers related to the activity of midbrain dopaminergic and GABAergic neurons are associated with this model. We used in situ hybridization histochemistry to assess expression of mRNAs for dopamine transporter (DAT), tyrosine hydroxylase (TH) and glutamate decarboxylase‐67 (GAD67) in the midbrain of adult rats with neonatal and adult ibotenic acid lesions of the ventral hippocampus. Neonatally lesioned rats showed in adulthood significantly reduced expression of DAT mRNA in the substantia nigra and the ventral tegmental area but no changes in the expression of TH and GAD67 mRNAs in these midbrain regions. Adult lesioned rats showed no changes in the expression of any of these genes. As the neonatal ventral hippocampal lesion reproduces many aspects of schizophrenia and is used as an animal model of this disorder, these results suggest that the reduction in DAT mRNA could result from developmental neuropathology in the ventral hippocampus and may thus represent a molecular substrate of the disease process.
Rapid activation of presynaptic nicotinic acetylcholine receptors by nerve‐released transmitter
Authors: Rogers Marc , Sargent Peter B. 
Published: December 2004

AbstractNicotine's ability to enhance neurotransmitter release has implicated presynaptic nicotinic acetylcholine receptors (nAChRs) in synaptic modulation, but there are few examples where presynaptic nAChRs are known to be activated by nerve‐released transmitter. We searched for endogenous activation of presynaptic nAChRs in the calyceal nerve terminals of the chick ciliary ganglion by imaging presynaptic calcium transients using dextran‐coupled indicator dyes. The amplitude of Ca2+ signals recorded in individual nerve terminals was frequency dependent over 2–50 Hz. Calcium transients evoked by stimulation of the preganglionic nerve were significantly reduced (≈10–15%) by the nonspecific nAChR antagonist d‐tubocurarine (d‐TC; 100 µm) and the α7‐specific antagonist methyllycaconitine (20–50 nm) but were not affected by 10 µm dihydro‐β‐erythroidine, which should inhibit several non‐α7 nAChRs. Feedback was rapid and did not require a stimulation‐dependent build‐up of transmitter, as d‐TC and MLA reduced the amplitude of the first calcium transient in a 2‐Hz train. Choline is an agonist at α7 nAChRs but is not the sole agonist in this system, as inhibition of acetylcholinesterase by echothiophate failed to reduce calcium transients. These results show that nerve‐released acetylcholine (ACh) feeds back onto presynaptic α7 nAChRs to enhance calcium signals within the terminal. This feedback may help maintain the high rate of transmission at this cholinergic synapse.
Effector‐independent representations of simple and complex imagined finger movements: a combined fMRI and TMS study
Authors: Kuhtz‐Buschbeck J. P. , Mahnkopf C. , Holzknecht C. , Siebner H. , Ulmer S. , Jansen O. 
Published: December 2004

AbstractKinesthetic motor imagery and actual execution of movements share a common neural circuitry. Functional magnetic resonance imaging was used in 12 right‐handed volunteers to study brain activity during motor imagery and execution of simple and complex unimanual finger movements of the dominant and the nondominant hand. In the simple task, a flexible object was rhythmically compressed between thumb, index and middle finger. The complex task was a sequential finger‐to‐thumb opposition movement. Premotor, posterior parietal and cerebellar regions were significantly more active during motor imagery of complex movements than during mental rehearsal of the simple task. In 10 of the subjects, we also used transcranial magnetic brain stimulation to examine corticospinal excitability during the same motor imagery tasks. Motor‐evoked potentials increased significantly over values obtained in a reference condition (visual imagery) during imagery of the complex, but not of the simple movement. Imagery of finger movements of either hand activated left dorsal and ventral premotor areas and the supplementary motor cortex regardless of task complexity. The effector‐independent activation of left premotor areas was particularly evident in the simple motor imagery task and suggests a left hemispherical dominance for kinesthetic movement representations in right‐handed subjects.
Convergent responses of Barrington's nucleus neurons to pelvic visceral stimuli in the rat: a juxtacellular labelling study
Authors: Rouzade‐Dominguez Marie‐Laure , Pernar Luise , Beck Sheryl , Valentino Rita J. 
Published: December 2004

AbstractBarrington's nucleus impacts on bladder and distal colon function and relays pelvic visceral information to the forebrain. This study investigated processing of information from the bladder and the distal colon by Barrington's nucleus in the rat. The responses of individual Barrington's nucleus neurons to bladder and/or colon distention were characterized using extracellular recording and the recorded neurons were identified using juxtacellular labelling. Most neurons within Barrington's nucleus (79%) were activated by bladder distention, consistent with its role as a pontine micturition centre. Although no neurons were selectively responsive to colon distention, the majority of bladder‐responsive neurons (73%) were also activated by colon distention. In a second study, Barrington's nucleus neurons were characterized with respect to their response to colon distention and their immunoreactivity for the stress‐related neuropeptide corticotropin‐releasing factor (CRF). Of 30 labelled neurons in the central part of Barrington's nucleus, 53% were activated by colon distention and 63% of these were CRF‐ir. This is the first report demonstrating that Barrington's nucleus neurons are responsive to colon distention. The results provide evidence for convergence of information from the bladder and the colon onto individual Barrington's nucleus neurons. Taken with evidence that many Barrington's nucleus neurons are synaptically linked to the bladder and colon, the present study suggests a role for these neurons in coordinating peripheral parasympathetic and central responses to both viscera and implicate CRF as a neurotransmitter in this function. Dysfunctions in this circuit may underlie the coexistence of colon and bladder symptoms observed in functional bowel disorders.
HAP1 facilitates effects of mutant huntingtin on inositol 1,4,5‐trisphosphate‐induced Ca2+ release in primary culture of striatal medium spiny neurons
Authors: Tang Tie‐Shan , Tu Huiping , Orban Paul C. , Chan Edmond Y. W. , Hayden Michael R. , Bezprozvanny Ilya 
Published: December 2004

AbstractHuntington's disease is caused by polyglutamine expansion (exp) in huntingtin (Htt). Htt‐associated protein‐1 (HAP1) was the first identified Htt‐binding partner. The type 1 inositol (1,4,5)‐trisphosphate receptor (InsP3R1) is an intracellular Ca2+ release channel that plays an important role in neuronal function. Recently, we identified a InsP3R1–HAP1A–Htt ternary complex in the brain and demonstrated that Httexp, but not normal Htt, activates InsP3R1 in bilayers and facilitates InsP3R1‐mediated intracellular Ca2+ release in medium spiny striatal neurons [MSN; T.‐S. Tang et al. (2003) Neuron, 39, 227–239]. Here we took advantage of mice with targeted disruption of both HAP1 alleles (HAP1 –/–) to investigate the role of HAP1 in functional interactions between Htt and InsP3R1. We determined that: (i) HAP1 is expressed in the MSN; (ii) HAP1A facilitates functional effects of Htt and Httexp on InsP3R1 in planar lipid bilayers; (iii) HAP1 is required for changes in MSN basal Ca2+ levels resulting from Htt or Httexp overexpression; (iv) HAP1 facilitates potentiation of InsP3R1‐mediated Ca2+ release by Httexp in mouse MSN. Our present results indicate that HAP1 plays an important role in functional interactions between Htt and InsP3R1.
The role of MAP kinases in rapid gene induction after lesioning of the rat sciatic nerve
Authors: Zrouri H. , Le Goascogne C. , Li W. W. , Pierre M. , Courtin F. 
Published: December 2004

AbstractLesion of the sciatic nerve caused a rapid activation of p38MAP kinase in the injured nerve adjacent to the site of transection. This activation was detectable 3 min after lesioning, increased during the next 15 min and remained high for several hours. Erk1/2 activation was also observed as early as 15 min after lesioning. Activation of these MAP kinases was seen in both the external sheaths and the endoneurium. The separation of the external sheaths from the endoneurium accelerated the p38MAP kinase activation. To evaluate whether the injury‐activated MAP kinase cascades are implicated in the rapid gene induction observed after nerve lesion, experiments were performed with an ex vivo model. Segments of sciatic nerves were incubated in oxygenated Krebs–Ringer buffer. MAP kinases were activated at 15 min and remained active after 6 h. Induction of mRNA was also observed for nerve growth factor (NGF), interleukin 6 (IL‐6), leukaemia inhibitory factor (LIF) and deiodinases of type 2 (D2) and type 3 (D3). Thus, the ex vivo model mimics events occurring in the animal after nerve section. Finally, nerve segments were incubated in the presence of specific inhibitors of Erk1/2 activation (U0126) and of p38MAP kinase activity (SB203580). U0126 inhibited D3, LIF and to a lesser extent NGF mRNA induction, but did not affect significantly the induction of D2 and IL‐6 mRNAs. SB203580 inhibited the expression of the genes for D3 and LIF. We conclude that MAP kinase cascades, activated by nerve transection, are involved in the rapid gene induction in the nerve.