bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastro‐oesophageal reflux of liquids and gas during transient lower oesophageal sphincter relaxations
Authors: Bredenoord A. J. , Weusten B. L. A. M. , Timmer R. , Smout A. J. P. M.
Published: June 2006

Abstract  Some transient lower oesophageal sphincter relaxations (TLOSRs) are accompanied by gastro‐oesophageal reflux and others are not. We aimed to investigate what factors determine the occurrence and type of reflux during TLOSRs. In 12 healthy subjects prolonged high‐resolution manometry was performed. Reflux was detected using pH‐impedance monitoring. A total of 219 TLOSRs were detected; no differences were observed between the duration of TLOSRs with liquid‐containing reflux (20.2 ± 1.0 s), gas reflux (17.0 ± 1.0 s) and no reflux (19.0 ± 1.0 s). Trans‐sphincteric pressure gradient was similar in TLOSRs with liquid reflux (1.6 ± 0.1 kPa), gas reflux (1.5 ± 0.1 kPa) and no reflux (1.7 ± 0.3 kPa). Prevalence, duration and amplitude of oesophageal pre‐contractions and sphincteric after‐contractions were not different for TLOSRs with and without reflux. The total number of TLOSRs decreased significantly from 8.2 ± 0.8 in the first to 5.7 ± 0.5 in the second and 4.4 ± 0.6 in the third 70‐min recording period. The number of TLOSRs accompanied by liquid‐containing reflux decreased from 4.7 ± 0.9 to 3.0 ± 0.4 to 1.6 ± 0.4, while the numbers of TLOSRs with gas reflux remained unchanged (2.1 ± 0.6–2.1 ± 0.7–2.2 ± 0.6). Besides, time after the meal, no differences were observed in the characteristics of TLOSRs with and without gastro‐oesophageal reflux. We conclude that factors, other than TLOSR characteristics, are important of whether or not a TLOSR is reflux‐related.
Involvement of cannabinoid receptors in inflammatory hypersensitivity to colonic distension in rats
Authors: Sanson M. , Bueno L. , Fioramonti J.
Published: June 2006

Abstract  Activation of cannabinoid CB1 and CB2 receptors is known to attenuate nociception and hyperalgesia in somatic inflammatory conditions. The aim of this study was to determine whether cannabinoids modulate colonic sensitivity in basal and inflammatory conditions. The effects of CB1 and CB2 receptor agonists and antagonists on the abdominal contractile response to colorectal distension (CRD) in basal conditions and after 2,4,6‐trinitrobenzenesulphonic acid‐induced colitis were investigated. As previously described, colitis triggered a hypersensitivity to CRD. In basal conditions, both CB1 (WIN 55212‐2) and CB2 (JWH 015) agonists reduced the abdominal response to CRD at a dose of 1 mg kg−1, i.p. Both compounds were active at a lower dose (0.1 mg kg−1) abolishing the hypersensitivity induced by colitis. Administered alone, CB1 (Rimonabant) and CB2 (SR 144528) receptor antagonists (10 mg kg−1) had no effect on basal sensitivity. In contrast, the CB1, but not the CB2, receptor antagonist enhanced colitis‐induced hyperalgesia. It is concluded that colonic inflammation enhances the antinociceptive action of CB1 and CB2 receptor agonists, and activates an endogenous, CB1 receptor mediated, antinociceptive pathway.
Alteration of T‐cell Receptor Repertoires During Thymic T‐cell Development
Authors: Matsutani T. , Ohmori T. , Ogata M. , Soga H. , Yoshioka T. , Suzuki R. , Itoh T.
Published: June 2006

The majority of thymocytes die in the thymus, whereas small populations of T cells that are able to specifically recognize an antigen are considered to survive. Although the thymic selection is thought to have a profound effect on T‐cell receptor (TCR) repertoire, little is known how TCR repertoire is formed during the thymocyte developmental process. We examined TCRα‐ and β‐chain variable regions (TCRAV and TCRBV) repertoire in thymic T‐cell subpopulations from mice bearing different major histocompatibility (MHC) haplotypes. In Balb/c mice, but not C57BL/6, remarkable alterations of the TCR repertoire were observed in mature T‐cell subpopulations as previously reported. In contrast, there were no significant differences of TCRBV repertoire between DN3 (CD25+CD44−) and DN4 (CD25−CD44−), and between DN4 and DP. These results suggest that (1) TCR repertoire of mature T cells was formed mainly under the influence of endogenous superantigens, while MHC haplotypes played the least role; (2) the ‘β‐selection’ process during immature stages had little impact on TCRBV repertoire formation; and (3) TCR repertoire in immature T‐cell subpopulations was extremely similar between different strains of mice. We thus consider that pre‐selection TCR repertoire in immature T cells could be determined by some genetic factors conserved among different strains.
Extrusion vs. accretion at the frictional–viscous décollement transition in experimental thrust wedges: the role of convergence velocity
Authors: Luján María , Storti Fabrizio , Rossetti Federico , Crespo‐Blanc Ana
Published: June 2006

In many cases, thrust wedges accreted at shallow crustal levels show an across‐strike rheological variability along the basal décollement, notably from brittle to ductile behaviour. In this paper, we illustrate the results of sandbox analogue modelling research devoted to studying the influence of convergence velocity on wedge architecture when laterally juxtaposed frictional and viscous materials occur along the basal décollement of accreting thrust wedges. Our results show that slow convergence favours a near symmetrical distribution of thrust vergence within wedge sectors accreted above viscous décollement material, whereas fast convergence favours vergence asymmetry. In particular, at fast convergence rates the hinterlandward extrusion of viscous décollement material at the toe of the frictional wedge is favoured and contributed to accommodate a significant amount of the total contraction.

Terra Nova, 18, 241–247, 2006
Phloem flow strongly influences the systemic spread of silencing in GFP Nicotiana benthamiana plants
Authors: Tournier Barthélémy , Tabler Martin , Kalantidis Kriton
Published: June 2006

The term ‘RNA silencing’ describes a process that results in the specific degradation of an RNA target. In plants, silenced tissues can initiate the spreading of the process into non‐silenced regions by a mobile signal that can be transmitted over long distances. In the present work, we made use of a modified grafting approach to elucidate the driving force behind long‐distance transport of the silencing signal. We made reciprocal grafts of two GFP‐transgenic Nicotiana benthamiana lines, the non‐silenced line 16c (sensor) and the silenced line 6.4 (inducer). We show that the direction of systemic spread of silencing from inducer to sensor can be manipulated by altering sink/source relations in the plant. Using radioactive phosphate as a phloem tracer, we demonstrated that plants that transmitted silencing from silenced scion to non‐silenced rootstock had developed a persisting phloem flow from scion to rootstock. These data provide experimental proof of what has been hypothesized so far, that the silencing signal travels via phloem from source to sink. We present here evidence that the appearance of systemic silencing is not an accidental stochastic process, but can be predicted on the basis of the direction of phloem flow.
Two cell‐cycle regulated SET‐domain proteins interact with proliferating cell nuclear antigen (PCNA) in Arabidopsis
Authors: Raynaud Cécile , Sozzani Rosangela , Glab Nathalie , Domenichini Séverine , Perennes Claudette , Cella Rino , Kondorosi Eva , Bergounioux Catherine
Published: June 2006

The proliferating cell nuclear antigen (PCNA) functions as a sliding clamp for DNA polymerase, and is thus a key actor in DNA replication. It is also involved in DNA repair, maintenance of heterochromatic regions throughout replication, cell cycle regulation and programmed cell death. Identification of PCNA partners is therefore necessary for understanding these processes. Here we identify two Arabidopsis SET‐domain proteins that interact with PCNA: ATXR5 and ATXR6. A truncated ATXR5Δex2, incapable of interacting with PCNA, also occurs in planta. ATXR6, upregulated during the S phase, is upregulated by AtE2F transcription factors, suggesting that it is required for S‐phase progression. The two proteins differ in their subcellular localization: ATXR5 has a dual localization in plastids and in the nucleus, whereas ATXR6 is solely nuclear. This indicates that the two proteins may play different roles in plant cells. However, overexpression of either ATXR5 or ATXR6 causes male sterility because of the degeneration of defined cell types. Taken together, our results suggest that both proteins may play a role in the cell cycle or DNA replication, and that the activity of ATXR5 may be regulated via its subcellular localization.
Specific fungal exposures, allergic sensitization, and rhinitis in infants
Authors: Osborne Melissa , Reponen Tiina , Adhikari Atin , Cho Seung‐Hyun , Grinshpun Sergey A. , Levin Linda , Bernstein David I. , LeMasters Grace
Published: June 2006

Indoor air quality has become increasingly important as we live in a society where the majority of our time is spent indoors. Specific attention has been drawn to airborne fungal spores as a factor affecting indoor air quality. This study targeted shortcomings of other studies by utilizing long‐term air sampling and total fungal spore enumeration to determine associations between health outcomes and fungal spore concentrations. Infants (n = 144) were clinically evaluated and had skin prick tests (SPT) for 17 allergens. Airborne fungal spores were collected using a Button Personal Inhalable Sampler (SKC Inc.) for 48 h at a flow rate of 4 l/min. Sampling was conducted in the spring (March–May) or fall (August–October) in 2003–2004. Fungal spores were analyzed using microscopy‐based total counting and identified to the genus/group level. Total spore and individual genus concentrations were analyzed for associations with rhinitis and positive SPT results. Overall, concentrations varied widely, between <2 and 2294 spores/m3. While no relationship was observed between SPT(+) and total fungal counts, several significant associations were found when analysis was conducted on the various fungal genera and health outcomes. Positive associations were obtained between: Basidiospores and rhinitis (p < 0.01), Penicillium/Aspergillus and SPT(+) to any allergen (p < 0.01), and Alternaria and SPT(+) to any allergen (p < 0.01). Inverse associations were found between: Cladosporium and SPT(+) to any allergen (p < 0.05), and Cladosporium and SPT(+) to aeroallergens (p < 0.05). This study indicates that health outcome may vary by fungal genera; some fungal types may have sensitizing effects while others may have a beneficial role.
Fracture toughness analysis of laser‐beam‐welded superalloys Inconel 718 and 625
Authors: YENI C. , KOÇAK M.
Published: June 2006

In this study, two 3.2‐mm thick Ni‐base superalloys, Inconel 718 and 625, have been laser‐beam‐welded by a 6‐kW CO2 laser and their room temperature fracture toughness properties have been investigated. Fracture toughness behaviour of the base metal (BM), fusion zone (FZ) and heat affected zone (HAZ) regions was determined in terms of crack tip opening displacement (CTOD) using compact tension‐type (C(T)) specimens. Laser‐beam‐weld regions showed no significant strength overmatching in both alloys. Ductile crack growth analysis (R‐curve) also showed that both materials exhibited similar behaviour. Compared to the BM there is a slight decrease in fracture toughness of the fusion and the HAZ.
Towards a strong virtue ethics for nursing practice
Authors: Armstrong Alan E.
Published: June 2006

Abstract Illness creates a range of negative emotions in patients including anxiety, fear, powerlessness, and vulnerability. There is much debate on the ‘therapeutic’ or ‘helping’ nurse–patient relationship. However, despite the current agenda regarding patient‐centred care, the literature concerning the development of good interpersonal responses and the view that a satisfactory nursing ethics should focus onpersonsandcharacter traitsrather thanactions, nursing ethics is dominated by the traditional obligation, act‐centred theories such as consequentialism and deontology. I critically examine these theories and the role of duty‐based notions in both general ethics and nursing practice. Because of well‐established flaws, I conclude that obligation‐based moral theories are incomplete and inadequate for nursing practice. I examine the work of Hursthouse on virtue ethics’ action guidance and the v‐rules. I argue that the moral virtues and a strong (action‐guiding) version of virtue ethics provide a plausible and viable alternative for nursing practice. I develop an account of a virtue‐based helping relationship and a virtue‐based approach to nursing. The latter is characterized by three features: (1) exercising the moral virtues such as compassion; (2) using judgement; and (3) using moral wisdom, understood to include at least moral perception, moral sensitivity, and moral imagination. Merits and problems of the virtue‐based approach are examined. I relate the work of MacIntyre to nursing and I conceive nursing as a practice: nurses who exercise the virtues and seek the internal goods help to sustain the practice of nursing and thus prevent the marginalization of the virtues. The strong practice‐based version of virtue ethics proposed is context‐dependent, particularist, and relational. Several areas for future philosophical inquiry and empirical nursing research are suggested to develop this account yet further.
What should other healthcare professions learn from nursing ethics
Authors: Holm Søren
Published: June 2006

Abstract  This paper analyses the question what other healthcare professions should learn from nursing ethics, e.g. what should medical ethics learn from nursing ethics. I first analyse and reject all strong versions of the claim that nursing ethics is unique, because nursing is a unique practice. I then move to the question of whether the link between nursing ethics and nursing theory can be a model for other areas of healthcare ethics. I provide an analysis of the possibility of creating a theory of medicine and find that there cannot be a theory of medicine, and I argue briefly that this finding is also applicable to nursing. If there cannot be a theory of nursing, this entails that nursing ethics cannot be justifiably based on such a theory. In the final section, I then analyse the success of nursing ethics in resisting certain of the vices of Anglo‐American analytic ethics, in particular the reductionism and individualism that characterizes much of healthcare ethics. I conclude that other healthcare ethics could usefully learn from this aspect of nursing ethics.
Neurocutaneous syndrome with mental delay, autism, blockage in intracellular vescicular trafficking and melanosome defects
Authors: Buoni S. , Zannolli R. , De Santi M. , Macucci F. , Hayek J. , Orsi A. , Scarinci R. , Buscalferri A. , Cuccia A. , Zappella M. , Miracco C.
Published: June 2006

We evaluated a 11‐year‐old male patient with mental delay, autism and brownish and whitish skin spots. The former resembled those of neurofibromatosis, the latter those of tuberous sclerosis. The patient received a complete clinical work‐up to exclude neurofibromatosis, tuberous sclerosis, or any other known neurocutaneous disease, with biochemistry, chromosome analysis and analysis of skin specimens. Being all the other tests not significant, two main ultrastructural defects were observed. The first was a blockage in intracellular vescicular trafficking with sparing of the mitochondria; the second an aberrant presence of melanosomes in vacuoles of several cell lines and abnormal transfer of these organelles to keratinocytes. This patient presented with a unique clinical picture distinct from neurofibromatosis or tuberous sclerosis or any other known neurocutaneous disease. The ultrastructural abnormalities suggested a defect in cell trafficking involving several cell lines and compartments.
European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy*
Authors: Van Schaik I. N. , Bouche P. , Illa I. , Léger J‐M. , Van den Bergh P. , Cornblath D. R. , Evers E. M. A. , Hadden R. D. M. , Hughes R. A. C. , Koski C. L. , Nobile‐Orazio E. , Pollard J. , Sommer C. , Van Doorn P. A.
Published: June 2006

Several diagnostic criteria for multifocal motor neuropathy have been proposed in recent years and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. The objectives were to prepare consensus guidelines on the definition, investigation and treatment of multifocal motor neuropathy. Disease experts and a patient representative considered references retrieved from MEDLINE and the Cochrane Library in July 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed good practice points to define clinical and electrophysiological diagnostic criteria for multifocal motor neuropathy and investigations to be considered. The principal recommendations and good practice points were: (i) IVIg (2 g/kg given over 2–5 days) should be considered as the first line treatment (level A recommendation) when disability is sufficiently severe to warrant treatment. (ii) Corticosteroids are not recommended (good practice point). (iii) If initial treatment with IVIg is effective, repeated IVIg treatment should be considered (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the individual response (good practice point). Typical treatment regimens are 1 g/kg every 2–4 weeks or 2 g/kg every 4–8 weeks (good practice point). (iv) If IVIg is not or not sufficiently effective then immunosuppressive treatment may be considered. Cyclophosphamide, ciclosporin, azathioprine, interferon beta1a, or rituximab are possible agents (good practice point). (v) Toxicity makes cyclophosphamide a less desirable option (good practice point).
EFNS guideline on neuroimaging in acute stroke. Report of an EFNS task force
Authors: Masdeu J. C. , Irimia P. , Asenbaum S. , Bogousslavsky J. , Brainin M. , Chabriat H. , Herholz K. , Markus H. S. , Martínez‐Vila E. , Niederkorn K. , Schellinger P. D. , Seitz R. J.
Published: June 2006

Neuroimaging techniques are necessary for the evaluation of stroke, one of the leading causes of death and neurological impairment in developed countries. The multiplicity of techniques available has increased the complexity of decision making for physicians. We performed a comprehensive review of the literature in English for the period 1965–2005 and critically assessed the relevant publications. The members of the panel reviewed and corrected an initial draft, until a consensus was reached on recommendations stratified according to the European Federation of Neurological Societies (EFNS) criteria. Non‐contrast computed tomography (CT) scan is the established imaging procedure for the initial evaluation of stroke patients. However, magnetic resonance imaging (MRI) has a higher sensitivity than CT for the demonstration of infarcted or ischemic areas and depicts well acute and chronic intracerebral hemorrhage. Perfusion and diffusion MRI together with MR angiography (MRA) are very helpful for the acute evaluation of patients with ischemic stroke. MRI and MRA are the recommended techniques for screening cerebral aneurysms and for the diagnosis of cerebral venous thrombosis and arterial dissection. For the non‐invasive study of extracranial vessels, MRA is less portable and more expensive than ultrasonography but it has higher sensitivity and specificity for carotid stenosis. Transcranial Doppler is very useful for monitoring arterial reperfusion after thrombolysis, for the diagnosis of intracranial stenosis and of right‐to‐left shunts, and for monitoring vasospasm after subarachnoid hemorrhage. Currently, single photon emission computed tomography and positron emission tomography have a more limited role in the evaluation of the acute stroke patient.
Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies (EFNS) and the Movement Disorder Society‐European Section (MDS‐ES). Part II: late (complicated) Parkinson's disease
Authors: Horstink M. , Tolosa E. , Bonuccelli U. , Deuschl G. , Friedman A. , Kanovsky P. , Larsen J. P. , Lees A. , Oertel W. , Poewe W. , Rascol O. , Sampaio C.
Published: June 2006

To provide evidence‐based recommendations for the management of late (complicated) Parkinson's disease (PD), based on a review of the literature. Complicated PD refers to patients suffering from the classical motor syndrome of PD along with other motor or non‐motor complications, either disease‐related (e.g. freezing) or treatment‐related (e.g. dyskinesias or hallucinations). MEDLINE, Cochrane Library and INAHTA database literature searches were conducted. National guidelines were requested from all EFNS societies. Non‐European guidelines were searched for using MEDLINE. Part II of the guidelines deals with treatment of motor and neuropsychiatric complications and autonomic disturbances. For each topic, a list of therapeutic interventions is provided, including classification of evidence. Following this, recommendations for management are given, alongside ratings of efficacy. Classifications of evidence and ratings of efficacy are made according to EFNS guidance. In cases where there is insufficient scientific evidence, a consensus statement (‘good practice point’) is made.
Rizatriptan Vs. Rizatriptan Plus Trimebutine for the Acute Treatment of Migraine: A Double-Blind, Randomized, Cross-Over, Placebo-Controlled Study
Authors: Krymchantowski AV , Filho PFM , Bigal ME
Published: June 2006

Gastroparesis frequently happens during migraine attacks, postponing the onset of action of orally administered drugs. Furthermore, triptans seem to work better in the earlier phases of the migraine attacks. Therefore, associating a gastrokinetic drug with a triptan may translate into better efficacy and higher consistency of response. Trimebutine is an opioid derivative with exclusive action on receptors of the Meissner and Auerbach plexus throughout the digestive tube. It has no absorption or central penetration. Herein we contrast the combination of rizatriptan plus trimebutine with rizatriptan alone in the acute treatment of migraine. Forty patients with migraine consecutively seen in our clinic were randomized to treat two consecutive moderate or severe attacks with one tablet of 10 mg rizatriptan plus one capsule of 200 mg trimebutine and two attacks with the same triptan and placebo, in counterbalanced order. We collected information on the severity of the attack, as well as presence of nausea and photophobia at the time of drug intake, and after 1, 2 and 4 h. Recurrence and adverse events were also contrasted. Sixty-four attacks were treated with each drug regimen. At 1 h post-dose, 30 (46.8±) of 64 attacks treated with the combination resolved completely, vs. eight (12.5±) of the rizatriptan-treated attacks, a difference of 34± ( P < 0.01). At 2 h postdose, 47 (73.4±) attacks treated with the combination vs. 20 (31.2±) of those treated with rizatriptan alone resolved completely, a difference of 42± (95± confidence interval 26, 58, P < 0.001). Regarding nausea and photophobia, the combination was also associated with significantly better response. Recurrence was similar among the two drug regimens, as well as adverse events. The combination rizatriptan and trimebutine is more effective than rizatriptan alone. The combination does not increase adverse events or recurrence of pain.
Objective Assessment of Cortical Excitability in Migraine With and Without Aura
Authors: Chronicle EP , Pearson AJ , Mulleners WM
Published: June 2006

Recent progress in the genetics of migraine has refocused attention on cortical dysfunction as an important component of the pathophysiology of this disorder. In previous work, we have demonstrated functional changes in the visual cortex of migraine patients, using an objective transcranial magnetic stimulation technique, termed magnetic suppression of perceptual accuracy (MSPA). This study aimed to replicate previous findings in migraine with aura (MA) and to use the technique to examine migraine without aura (MoA). Eight MA patients, 14 MoA patients and 13 migraine-free controls participated. MSPA assessments were undertaken using a standardized protocol in which computer-presented letter targets were followed at a variable delay interval by a single magnetic pulse delivered over the occiput. MSPA performance is expressed as a profile of response accuracy across target-pulse delay intervals. The profiles of migraine-free controls exhibited a normal U-shape. MA patients had significantly shallower profiles, showing little or no suppression at intermediate delay intervals. MoA patients had profiles that were similar to controls. Recent animal evidence strongly indicates that the U-shape of the normal MSPA function is caused by preferential activation of inhibitory neurons. Shallower MPSA profiles in MA patients are therefore likely to indicate a functional hyperexcitability caused by impaired inhibition. The finding of normal MPSA profiles in MoA patients is novel and will require further investigation.
Mesodermal cell types induce neurogenesis from adult human hippocampal progenitor cells
Authors: Hermann Andreas , Maisel Martina , Liebau Stefan , Gerlach Manfred , Kleger Alexander , Schwarz Johannes , Kim Kwang‐Soo , Antoniadis Gregor , Lerche Holger , Storch Alexander
Published: June 2006

Neurogenesis in the adult human brain occurs within two principle neurogenic regions, the hippocampus and the subventricular zone (SVZ) of the lateral ventricles. Recent reports demonstrated the isolation of human neuroprogenitor cells (NPCs) from these regions, but due to limited tissue availability the knowledge of their phenotype and differentiation behavior is restricted. Here we characterize the phenotype and differentiation capacity of human adult hippocampal NPCs (hNPCs), derived from patients who underwent epilepsy surgery, on various feeder cells including fetal mixed cortical cultures, mouse embryonic fibroblasts (MEFs) and PA6 stromal cells. Isolated hNPCs were cultured in clonal density by transferring the cells to serum‐free media supplemented with FGF‐2 and EGF in 3% atmospheric oxygen. These hNPCs showed neurosphere formation, expressed high levels of early neuroectodermal markers, such as the proneural genes NeuroD1 and Olig2, the NSC markers Nestin and Musashi1, the proliferation marker Ki67 and significant activity of telomerase. The phenotype was CD15low/–, CD34–, CD45– and CD133–. After removal of mitogens and plating them on poly d‐lysine, they spontaneously differentiated into a neuronal (MAP2ab+), astroglial (GFAP+), and oligodendroglial (GalC+) phenotype. Differentiated hNPCs showed functional properties of neurons, such as sodium channels, action potentials and production of the neurotransmitters glutamate and GABA. Co‐culture of hNPCs with fetal cortical cultures, MEFs and PA6 cells increased neurogenesis of hNPCs in vitro, while only MEFs and PA6 cells also led to a morphological and functional neurogenic maturation. Together we provide a first detailed characterization of the phenotype and differentiation potential of human adult hNPCs in vitro. Our findings reinforce the emerging view that the differentiation capacity of adult hNPCs is critically influenced by non‐neuronal mesodermal feeder cells.
The brain glutamate system in liver failure
Authors: Vaquero Javier , Butterworth Roger F.
Published: June 2006

Liver failure results in significant alterations of the brain glutamate system. Ammonia and the astrocyte play major roles in such alterations, which affect several components of the brain glutamate system, namely its synthesis, intercellular transport (uptake and release), and function. In addition to the neurological symptoms of hepatic encephalopathy, modified glutamatergic regulation may contribute to other cerebral complications of liver failure, such as brain edema, intracranial hypertension and changes in cerebral blood flow. A better understanding of the cause and precise nature of the alterations of the brain glutamate system in liver failure could lead to new therapeutic avenues for the cerebral complications of liver disease.
The effects of ABCA1 on cholesterol efflux and Aβ levels in vitro and in vivo
Authors: Burns Mark P. , Vardanian Lilit , Pajoohesh‐Ganji Ahdeah , Wang Lili , Cooper Matthew , Harris Donnie C. , Duff Karen , Rebeck G. William
Published: June 2006

ABCA1 promotes cholesterol efflux from cells and is required for maintaining plasma cholesterol levels. Cholesterol homeostasis is important in the production of β‐amyloid (Aβ), a peptide that is overproduced in Alzheimer's disease (AD). Overexpression of ABCA1 can be achieved by stimulating Liver X Receptors (LXR), and changes in Aβ have been reported after LXR stimulation in vitro. To determine whether ABCA1 could alter endogenous Aβ levels, we used two different in vivo systems. We first examined the effects of an LXR agonist (TO‐901317) on wild‐type mice and found an increase in brain ABCA1 and apoE levels, which caused an increase in plasma cholesterol. This was accompanied by a decrease in brain Aβ levels. We then examined endogenous Aβ levels in ABCA1 knockout mice and found that, despite having no ABCA1, lowered brain apoE levels, and lowered plasma cholesterol, there was no change in Aβ levels. To assess these in vivo models in an in vitro system, we designed a model in which cholesterol transport via ABCA1 (or related transporters) was prevented. Switching off cholesterol efflux, even in the presence of TO‐901317, caused no change in Aβ levels. However, when efflux capability was restored, TO‐901317 reduced Aβ levels. These data show that promoting cholesterol efflux is a viable target for Aβ reducing strategies; however, knockout of cholesterol transporters is not sufficient to alter Aβin vitro or in vivo.
Evidence for L‐dopa incorporation into cell proteins in patients treated with levodopa
Authors: Rodgers Kenneth J. , Hume Peter M. , Morris John G. L. , Dean Roger T.
Published: June 2006

Levodopa (L‐dopa) is the most widely used agent for the symptomatic relief of Parkinson's disease. There is concern that chronic L‐dopa treatment may be detrimental, with some studies suggesting that L‐dopa may be neurotoxic. A potentially important mechanism whereby L‐dopa may exert neurotoxic effects has been overlooked: that of the incorporation of L‐dopa into proteins by protein synthesis. L‐Dopa competes with tyrosine as a substrate in protein synthesis in vitro. We provide evidence that L‐dopa can also be incorporated into proteins in vivo. Blood from L‐dopa‐treated and ‐non‐treated patients was separated into protein, erythrocyte and lymphocyte fractions and levels of protein‐incorporated dopa quantified by HPLC. Levels of protein‐incorporated dopa were significantly increased in lymphocyte cell proteins from L‐dopa‐treated patients. This has not arisen from oxidative pathways as there was no evidence of oxidative damage to proteins. In addition, there was no increase in protein‐incorporated dopa in erythrocytes, which are not actively synthesizing proteins. We suggest that protein‐incorporated dopa could also be generated in the CNS. The accumulation of protein‐incorporated dopa in cells is associated with oxidative stress and impaired function and could contribute to some of the problems associated with long‐term L‐dopa treatment.
IL‐1β induces a MyD88‐dependent and ceramide‐mediated activation of Src in anterior hypothalamic neurons
Authors: Davis Christopher N. , Tabarean Iustin , Gaidarova Svetlana , Behrens M. Margarita , Bartfai Tamas
Published: June 2006

The proinflammatory cytokine interleukin1β (IL‐1β), acting at IL‐1R1 receptors, affects neuronal signaling under both physiological and pathophysiological conditions. The molecular mechanism of the rapid synaptic actions of IL‐1β in neurons is not known. We show here that within minutes of IL‐1β exposure, the firing rate of anterior hypothalamic (AH) neurons in culture was inhibited. This effect was prevented by pre‐exposure of the cells to the Src family inhibitor, PP2, suggesting the involvement of Src in the hyperpolarizing effects of IL‐1β. The IL‐1β stimulation of neurons induced a rapid increase in the phosphorylation of the tyrosine kinase Src and kinase suppressor of Ras (ceramide activated protein kinase (CAPK)/KSR) in neurons grown on glia from IL‐1RI(–/–) mice. These effects of IL‐1β were dependent on the association of the cytosolic adaptor protein, MyD88, to the IL‐1 receptor, and on the activation of the neutral sphingomyelinase, leading to production of ceramide. A cell‐permeable analog of ceramide mimicked the effects of IL‐1β on the cultured AH neurons. These results suggest that ceramide may be the second messenger of the fast IL‐1β actions in AH neurons, and that this IL‐1β/ceramide pathway may underlie the fast non‐transcription‐dependent, electrophysiological effects of IL‐1β observed in AH neurons in vivo.
C/EBPβ couples dopamine signalling to substance P precursor gene expression in striatal neurones
Authors: Kovács Krisztián A. , Steinmann Myriam , Magistretti Pierre J. , Halfon Olivier , Cardinaux Jean‐René
Published: June 2006

Dopamine‐induced changes in striatal gene expression are thought to play an important role in drug addiction and compulsive behaviour. In this study we report that dopamine induces the expression of the transcription factor CCAAT/Enhancer Binding Protein β (C/EBP)‐β in primary cultures of striatal neurones. We identifed the preprotachykinin‐A (PPT‐A) gene coding for substance P and neurokinin‐A as a potential target gene of C/EBPβ. We demonstrated that C/EBPβ physically interacts with an element of thePPT‐Apromoter, thereby facilitating substance P precursor gene transcription. The regulation ofPPT‐Agene by C/EBPβ could subserve many important physiological processes involving substance P, such as nociception, neurogenic inflammation and addiction. Given that substance P is known to increase dopamine signalling in the striatum and, in turn, dopamine increases substance P expression in medium spiny neurones, our results implicate C/EBPβ in a positive feedback loop, changes of which might contribute to the development of drug addiction.
Modulation of Ca2+ signals by phosphatidylinositol‐linked novel D1 dopamine receptor in hippocampal neurons
Authors: Ming Yuling , Zhang Hai , Long Lihong , Wang Fang , Chen Jianguo , Zhen Xuechu
Published: June 2006

Recent evidence indicates the existence of a putative novel phosphatidylinositol‐linked D1 dopamine receptor in brain that mediates phosphatidylinositol hydrolysis via activation of phospholipase Cβ. The present work was designed to characterize the Ca2+ signals regulated by this phosphatidylinositol‐linked D1 dopamine receptor in primary cultures of hippocampal neurons. The results indicated that stimulation of phosphatidylinositol‐linked D1 dopamine receptor by its newly identified selective agonist SKF83959 induced a long‐lasting increase in basal [Ca2+]i in a time‐ and dose‐dependent manner. Stimulation was observable at 0.1 μm and reached the maximal effect at 30 μm. The [Ca2+]i increase induced by 1 μm SKF83959 reached a plateau in 5 ± 2.13 min, an average 96 ± 5.6% increase over control. The sustained elevation of [Ca2+]i was due to both intracellular calcium release and calcium influx. The initial component of Ca2+ increase through release from intracellular stores was necessary for triggering the late component of Ca2+ rise through influx. We further demonstrated that activation of phospholipase Cβ/inositol triphosphate was responsible for SKF83959‐induced Ca2+ release from intracellular stores. Moreover, inhibition of voltage‐operated calcium channel or NMDA receptor‐gated calcium channel strongly attenuated SKF83959‐induced Ca2+ influx, indicating that both voltage‐operated calcium channel and NMDA receptor contribute to phosphatidylinositol‐linked D1 receptor regulation of [Ca2+]i.
Toxic torts: arsenic poisoning in Bangladesh and the legal geographies of responsibility
Authors: Atkins Peter J , Manzurul Hassan M , Dunn Christine E
Published: June 2006

Tubewells have been so popular in rural Bangladesh that about 12 million have been installed, yielding water that is convenient, free and low in bacteria. But every fourth well is polluted with arsenic, with the result that millions of people are exposed to a severe environmental hazard. We explore this crisis from the viewpoint of legal geographies. The case of Sutradhar v NERC is taken as an exemplar of a debate about ‘proximity’ between scientific consultants and aid donors on the one hand, and their clients in poor countries on the other. In short, the article is about the desirability of bringing responsibility into line with supposed generosity.
Pediatric Anogenital Warts: A 7‐Year Review of Children Referred to a Tertiary‐Care Hospital in Montreal, Canada
Authors: Marcoux Danielle , Nadeau Karine , McCuaig Catherine , Powell Julie , Oligny Luc L.
Published: June 2006

Abstract:  The objectives of this study were to delineate the clinical characteristics of a hospital‐referred pediatric population infected with anogenital warts and to investigate the possible relationships between human papillomavirus types and the identified clinical characteristics. Over a 7‐year period, 72 patients under the age of 12 years were seen at our dermatology clinic for anogenital warts, corresponding to a prevalence of 1.7/1000 in our patient population. Sixty‐four percent (46/72) were girls. Congenital, prenatal, ascending infections occurred in two subjects. The onset of anogenital warts occurred before age 2 in 28% and between 2 and 6 years of age in 62% of children and tended to be younger in boys. We identified unusual cutaneomucosal serotypes human papillomavirus 7 and 57 (three and eight instances, respectively). The modes of transmission of anogenital warts in children cannot be identified either by the clinical appearance of the lesions or by human papillomavirus typing. We conclude that the best way to identify possible sexual abuse is still by history taking, careful assessment of the socio‐clinical context, and physical examination.
Parvovirus B19 Infection in Children with Acute Illness and Rash
Authors: Pruksachatkunakorn Chulabhorn , Apichartpiyakul Nisarat , Kanjanaratanakorn Kittika
Published: June 2006

Abstract: Parvovirus B19 is responsible for a variety of cutaneous diseases, including erythema infectiosum and papular purpuric gloves‐and‐socks syndrome. It is also associated with other dermatologic diseases, such as systemic lupus erythematosus. To study the prevalence of parvovirus B19 infection in children with acute illness and rash, we did a prospective study of 110 children at the Chiang Mai University teaching hospital from January 2001 to November 2003. Sera from these patients were analyzed for immunoglobulin M and immunoglobulin G antibodies against human parvovirus B19 using enzyme‐linked immunosorbent assay techniques. From a total of 110 patients with acute illness and rash, there were paired serum samples for 90 patients and single serum sample for 20 patients. For those with paired serum samples, there were three patients with recent parvovirus B19 infection that presented with erythema infectiosum, urticaria, and lupus erythematosus, respectively. Immunoglobulin G antibodies were tested in serum samples of 103 children; 28.2% were positive. These data indicate that parvovirus B19 is not a common cause of acute illness and rash in children.
Cutis Laxa Type II and Wrinkly Skin Syndrome: Distinct Phenotypes
Authors: Gupta Neerja , Phadke Shubha R.
Published: June 2006

Abstract:  Cutis laxa is a heterogeneous group of disorders with variable phenotypes and inheritance patterns. Type II cutis laxa has features overlapping with wrinkly skin syndrome, as a result of which they are regarded as one disorder with a variable spectrum of severity by some authors. To overcome this existing confusion, we present three patients with cutis laxa type II and review the literature to highlight the important differentiating features between cutis laxa type II and wrinkly skin syndrome.
Cutaneous Amebiasis in a Child and Review of the Literature
Authors: Kenner Brandi M. , Rosen Theodore
Published: June 2006

Abstract:  Cutaneous amebiasis is a rare manifestation of infection with the parasite Entamoeba histolytica. We describe this infestation in a 9‐year‐old Mexican immigrant who presented with diarrhea and perianal ulcers. To our knowledge, this is only the tenth child with cutaneous amebiasis reported in the literature, and only the second from the United States. We review previous reports and emphasize the importance of a high index of clinical suspicion for early diagnosis and treatment to prevent potentially serious morbidity and even mortality.
Extensive Skin Calcifications in an Infant with Chronic Renal Failure: Metastatic Calcinosis Cutis
Authors: Tan Onder , Atik Bekir , Kizilkaya Ali , Ozer Erdener , Kavukcu Salih
Published: June 2006

Abstract:  Calcinosis cutis, one of the rare manifestations of systemic calcinosis, is characterized by the deposition of calcium and phosphate salts in the skin. Metastatic calcinosis, usually a late complication of chronic renal failure, arises from increased calcium or phosphate levels in the serum or both. Both sexes and all ages may be affected; however, cutaneous involvement is uncommon, particularly in children. We present the youngest patient, to our knowledge, with end‐stage renal disease and cutaneous metastatic calcification resulting from secondary hyperparathyroidism. A 2‐month‐old infant presented to the pediatric service with anuria and uremia. A renal biopsy specimen showed chronic tubulo‐interstitial nephritis. Indurated, firm, tender reddish papules were localized to both lower limbs, and extensive irregular nodules and plaques with ulceration and white stony contents were localized to the right upper limb. Topical antibiotic ointment was applied to the skin lesions to prevent secondary infection. However, acute peritonitis developed during peritoneal dialysis, and death occurred as a result of sepsis.
Multiple Erythematous Nodules and Ecthyma Gangrenosum as a Manifestation of Pseudomonas aeruginosa Sepsis in a Previously Healthy Infant
Authors: Duman Murat , Özdemir Durgül , Yiş Uluç , Köroğlu Tolga F. , Ören Oğuz , Berktaş Sema
Published: June 2006

Abstract:  Pseudomonas aeruginosa septicemia is rare in healthy infants and children. Also not common, dermatologic manifestations such as ecthyma gangrenosum and indurated erythematous nodular lesions may be the first signs of pseudomonas infection, or may appear later in the course of the disease. Peripheral facial paralysis and mastoiditis are also rare and serious complications of acute otitis media caused by P. aeruginosa. We report a previously healthy 6‐month‐old boy who had an uncommon presentation and rare complications during the course of P. aeruginosa sepsis.
A Child with Hypohidrotic Ectodermal Dysplasia with Features of a Collodion Membrane
Authors: Thomas Chad , Suranyi Emese , Pride Howard , Tyler William
Published: June 2006

Abstract:  Collodion membrane is a presenting phenotype common to several disorders, predominantly congenital ichthyoses. Seventy percent of infants born with hypohidrotic (anhidrotic) ectodermal dysplasia are noted by their parents to have significant scaling and peeling. Although dry skin is a frequently reported sign in children with hypohidrotic ectodermal dysplasia, only one French study has reported a true collodion membrane at birth. We suspect that scaling with features of collodion membrane is more common in infants than is reflected in the literature, and we describe another such infant, later diagnosed with hypohidrotic ectodermal dysplasia.
Richner–Hanhart Syndrome (Tyrosinemia II): Early Diagnosis of an Incomplete Presentation with Unusual Findings
Authors: Viglizzo Gian Maria , Occella Corrado , Bleidl Dario , Rongioletti Franco
Published: June 2006

Abstract:  We report a 2‐year‐old girl with an incomplete form of Richner–Hanhart syndrome (tyrosinemia II) whose presenting sign was the appearance of vesicles on the fingertips. In a few months these lesions evolved into typical hyperkeratotic plaques also involving the palms and soles. Photophobia and frequent tearing were observed but there was no intelligence impairment. Serum and urine tyrosine levels confirmed the diagnosis. A low tyrosine and phenylalanine diet permitted good control of the disease with a complete resolution of the oculo‐cutaneous symptoms in a month. We emphasize the importance of an early diagnosis of this syndrome to avoid the risk of mental retardation.
Acrodermatitis Enteropathica‐like Eruptions in a Child with Hartnup Disease
Authors: Seyhan Muammer Eşrefoğlu , Selimoğlu Mukadder Ayşe , Ertekin Vildan , Fidanoğlu Osman , Altınkaynak Sevin
Published: June 2006

Abstract:  Acrodermatitis enteropathica‐like eruptions, not related to zinc deficiency, have been rarely reported in some metabolic disorders. Reported patients usually had low levels of essential amino acids, particularly isoleucine. Here we report a girl who first presented with an acrodermatitis enteropathica‐like eruption and eventually had the diagnosis of Hartnup disease with a normal isoleucine level. We discuss the probable cause of her skin lesions and the differential diagnosis with pellagra.
Fatal Childhood Calciphylaxis in a 10‐Year‐Old and Literature Review
Authors: Feng Jing , Gohara Mona , Lazova Rossitza , Antaya Richard J.
Published: June 2006

Abstract:  Calciphylaxis is a rare but highly morbid disorder of vascular calcification and skin necrosis, affecting 1% to 4% of adults with end‐stage renal disease. Only three affected children have previously been described. We report an unusual instance of fatal calciphylaxis involving a 10‐year‐old boy, in the setting of sarcoidosis‐induced end‐stage renal disease. A review of pediatric calciphylaxis cases suggests: (a) increased risk in boys with end‐stage renal disease and secondary hyperparathyroidism; (b) frequent distal extremity and visceral organ involvement, (c) worse prognosis with acral necrosis, and (d) possible increased resistance to medical treatment compared to adult patients. Hyperesthetic pain is a common sentinel symptom, and soft tissue x‐rays or xeroradiography or both may aid in the diagnosis of pediatric calciphylaxis. Parathyroidectomy in combination with supportive medical management may be the best treatment option in stopping the progression of disease in the pediatric population.
Solitary Congenital Self‐Healing Reticulohistiocytosis in Monozygotic Twins
Authors: Ersoy‐Evans Sibel , Gursoy Tugba , Yigit Sule , Akcoren Zuhal , Sahin Sedef
Published: June 2006

Abstract:  We report monozygotic twins with congenital self‐healing reticulohistiocytosis, whose lesions initially presented as hemorrhagic bullae at birth with rapid progression into crusted papules the following day. Physical examination disclosed crusted papules on the right side of the neck of twin 1 and a similar solitary lesion on the lateral side of the right thumb of twin 2. Excisional biopsy specimen findings of the neck and thumb lesions were consistent with Langerhans cell histiocytosis, which was further confirmed by positive CD1a staining. The lesions resolved completely by 2 months with no evidence of recurrence or systemic involvement. Congenital self‐healing reticulohistiocytosis is a rare, self‐limited form of Langerhans cell histiocytosis. Although familial clustering in Langerhans cell histiocytosis was previously reported, to the best of our knowledge there is no report suggesting familial clustering in congenital self‐healing reticulohistiocytosis. Our patients are interesting in terms of raising the question of whether the presence of congenital self‐healing reticulohistiocytosis in monozygotic twins is implicative of a genetic role in its pathogenesis.