bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rotavirus double‐stranded RNA induces apoptosis and diminishes wound repair in rat intestinal epithelial cells
Authors: SATO AKIKO , IIZUKA MASAHIRO , NAKAGOMI OSAMU , SUZUKI MANABU , HORIE YASUO , KONNO SHIHO , HIRASAWA FUJIKO , SASAKI KENJI , SHINDO KENICHI , WATANABE SUMIO 
Published: March 2006

AbstractBackground:  Recent studies have shown that toll‐like receptor 3 (TLR3) recognizes double‐stranded RNA (dsRNA). Rotaviruses, having a dsRNA genome, infect intestinal epithelial cells (IEC) and cause acute gastroenteritis in young children. The aim of the present study was to clarify the pathophysiological function of rotavirus dsRNA in IEC.Methods:  Expression of TLR3 mRNA or protein in IEC cell lines (IEC‐6, HT‐29, Caco‐2) was assessed by reverse transcription polymerase chain reaction (RT–PCR), Western blot analysis or immunohistochemistry. Induction of cytokines (TNF‐α, interferon‐β, interleukin‐6) mRNA and activation of signal proteins (ERK1/2 MAPK and IκB‐α) in IEC after stimulation with rotavirus dsRNA were assessed by RT–PCR or Western blot analysis. IEC‐6 cells were wounded and cell migration into wound areas after stimulation with rotavirus dsRNA (1–25 µg/mL) was assessed. Induction of apoptosis after stimulation with rotavirus dsRNA was also assessed.Results:  Expression of TLR3 mRNA and TLR3 protein was detected in IEC. Expression of TLR3 mRNA in IEC‐6 tended to be up‐regulated by exposure to IFN‐γ. Induction of cytokine mRNA and activation of the signal proteins were detected after stimulation with rotavirus dsRNA. Apoptosis was induced and epithelial migration into the wound area was dose‐dependently diminished (44.1–94.4%, P < 0.01) by exposure to rotavirus dsRNA. Diminishment of wound repair was suppressed by anti‐TLR3 antibody or caspase inhibitor.Conclusion:  Rotavirus dsRNA induces severe apoptosis and diminishes wound repair in IEC through TLR3, which might be involved in the pathogenesis of rotavirus‐induced enteritis.
Late onset autoimmune thrombocytopenia associated with pegylated interferon‐α‐2b plus ribavirin treatment for chronic hepatitis C
Authors: Elefsiniotis Ioannis S , Pantazis Konstantinos D , Fotos Nikolaos V , Moulakakis Antonios , Mavrogiannis Christos 
Published: March 2006

AbstractInterferon‐induced, immune‐mediated, thrombocytopenia is a rare event. In this report the case is described of development of severe, reversible, autoimmune thrombocytopenia in a patient with chronic hepatitis C virus infection, 6 months after the discontinuation of pegylated interferon‐α‐2b plus ribavirin treatment. Physicians must be aware that autoimmune thrombocytopenia can occur even after the end of treatment, as a late onset complication, especially when using the pegylated forms of interferons, which have longer half‐lives and prolonged activity.
Population‐based study of the relationship between mutations in the hemochromatosis (HFE) gene and arthritis
Authors: Sherrington Colin A , Knuiman Matthew W , Divitini Mark L , Bartholomew Helen C , Cullen Digby J , Olynyk John K 
Published: March 2006

AbstractBackground and Aim:  Mutations in the hemochromatosis (HFE) gene are carried by one in three individuals of British Isles descent and may result in increased iron stores. These increased iron stores could potentially induce or exacerbate diseases, such as arthritis, in which iron has a role in pathogenesis. Although arthritis is a well‐known association of clinically overt hereditary hemochromatosis, controversy surrounds the role of mutations in the HFE gene as risk factors for arthritis. The aim of the present study was to determine whether mutations in the HFE gene are associated with an increased prevalence of arthritis.Methods:  A population‐based study was conducted in Busselton, Western Australia, of the prevalence of arthritis in 1372 individuals of British Isles descent. Participants completed a questionnaire and general physical examination. Analysis for C282Y and H63D HFE mutations was undertaken. Unadjusted and adjusted odds ratios (OR) were calculated for the relationship between HFE mutations and the prevalence of self‐reported, doctor‐diagnosed arthritis.Results:  There was no association between the presence of HFE mutations and the prevalence of self‐reported, doctor‐diagnosed arthritis (C282Y/wild type (WT) adjusted OR = 1.041 (95% confidence interval (CI) 0.68–1.61), H63D/WT OR = 0.76 (95% CI 0.53–1.08), C282Y/C282Y OR = 0.39 (95% CI 0.04–3.63), C282Y/H 63D OR = 0.808 (95% CI 0.27–2.42), H63D/H63D OR = 0.419 (95% CI 0.13–1.36)). Overall adjusted OR for arthritis in participants with one or more HFE mutations was 0.81 (95% CI 0.61–1.09).Conclusions:  Mutations of the HFE gene are not risk factors for arthritis in populations of British Isles descent.
Childhood pancreatitis
Authors: Nydegger Andy , Couper Richard T L , Oliver Mark R 
Published: March 2006

AbstractInflammation of the pancreas has many presentations in children and adolescents. The etiology is often elusive, with a great number of cases being idiopathic. However, there have been a number of recent advances in the areas of cell biology, genetics and imaging technology, which should be highlighted. Herein is provided a review for the reader with particular emphasis on some of these newer advances.
Asian contribution to living donor liver transplantation
Authors: Lee Sung‐Gyu 
Published: March 2006

AbstractAlthough the shortage of brain‐dead donor organs is a worldwide problem, the situation is especially serious in Asia because of various cultural and social reasons, and cadaveric organ donation remains below 5 per million population per year. Living donor liver transplantation (LDLT) could provide an alternative for liver graft for patients with acute and chronic end‐stage liver disease. This article introduces the important contributions to the development of LDLT by the leading Asian liver transplantation centers. The first successful adult LDLT using a left‐lobe graft was reported by Makuuchi et al. from Japan in 1994. To overcome the barrier of graft‐size matching for adult patients with use of a left‐lobe graft, a trial of adult LDLT using a right‐lobe graft with middle hepatic vein was reported with satisfactory outcome by Fan et al. from Hong Kong in 1997. Despite the impressive results of right‐lobe LDLT, considerable debate persists concerning donor safety. Lee et al. from Korea initiated modified right‐lobe liver grafting with interposition vein grafts to drain anterior segment and two left‐lobe liver grafting to overcome graft‐size insufficiency and to ensure donor safety in 1999 and 2000, respectively. In addition to technical innovations, indications for liver transplantation have been developed by Asian centers as LDLT activity has increased.
Hippocampal up‐regulation of NCAM expression and polysialylation plays a key role on spatial memory
Authors: Venero César , Herrero Ana I. , Touyarot Katia , Cambon Karine , López‐Fernández Miguel A. , Berezin Vladimir , Bock Elisabeth , Sandi Carmen 
Published: March 2006

AbstractMemory formation has been associated with structural and functional modifications of synapses. Cell adhesion molecules are prominent modulators of synaptic plasticity. Here, we investigated the involvement of the cell adhesion molecules, NCAM, its polysialylated state (PSA‐NCAM) and L1 in spatial learning‐induced synaptic remodeling and memory storage. A differential regulation of these adhesion molecules was found in the hippocampus of rats submitted to one training session in the spatial, but not cued, version of the Morris water maze. Twenty‐four hours after training, synaptic expression of NCAM and PSA‐NCAM was increased, whereas L1 appeared markedly decreased. The regulation of these molecules was spatial learning‐specific, except for L1 reduction, which could be attributed to swimming under stressful conditions rather than to learning. Subsequent psychopharmacological experiments were performed to address the functional role of NCAM and PSA‐NCAM in the formation of spatial memories. Rats received an intracerebroventricular injection of either a synthetic peptide (C3d) aimed to interfere with NCAM function, or endoneuraminidase, an enzyme that cleaves polysialic acid from NCAM. Both treatments affected acquisition of spatial information and lead to impaired spatial memory abilities, supporting a critical role of the observed learning‐induced up‐regulation of synaptic NCAM expression and polysialylation on spatial learning and memory. Therefore, our findings highlight NCAM as a learning‐modulated molecule critically involved in the hippocampal remodeling processes underlying spatial memory formation.
Differential effects of low glucose concentrations on seizures and epileptiform activity in vivo and in vitro
Authors: Kirchner Anne , Velíšková Jana , Velíšek Libor 
Published: March 2006

AbstractIn vivo, severe hypoglycemia is frequently associated with seizures. The hippocampus is a structure prone to develop seizures and seizure‐induced damage. Patients with repeated hypoglycemic episodes have frequent memory problems, suggesting impaired hippocampal function. Here we studied the effects of moderate hypoglycemia on primarily generalized flurothyl‐induced seizures in vivo and, using EEG recordings, we determined involvement of the hippocampus in hypoglycemic seizures. Moderate systemic hypoglycemia had proconvulsant effects on flurothyl‐induced clonic (forebrain) seizures. During hypoglycemic seizures, seizure discharges were recorded in the hippocampus. Thus, we continued the studies in combined entorhinal cortex–hippocampus slices in vitro. However, in vitro, decreases in extracellular glucose from baseline 10 mm to 2 or 1 mm did not induce any epileptiform discharges. In fact, low glucose (2 and 1 mm) attenuated preexisting low‐Mg2+‐induced epileptiform activity in the entorhinal cortex and hippocampal CA1 region. Osmolarity compensation in low‐glucose solution using mannitol impaired slice recovery. Additionally, using paired‐pulse stimuli we determined that there was no impairment of GABAA inhibition in the dentate gyrus during glucopenia. The data strongly indicate that, although forebrain susceptibility to seizures is increased during moderate in vivo hypoglycemia and the hippocampus is involved during hypoglycemic seizures, glucose depletion in vitro contributes to an arrest of epileptiform activity in the system of the entorhinal cortex–hippocampus network and there is no impairment of net GABAA inhibition during glucopenia.
Localization of metabotropic GABA receptor subunits GABAB1 and GABAB2 relative to synaptic sites in the rat developing cerebellum
Authors: Luján R. , Shigemoto R. 
Published: March 2006

AbstractThe highest densities of the two metabotropic GABA subunits, GABAB1 and GABAB2, have been reported as occurring around the glutamatergic synapses between Purkinje cell spines and parallel fibre varicosities. In order to determine how this distribution is achieved during development, we investigated the expression pattern and the cellular and subcellular localization of the GABAB1 and GABAB2 subunits in the rat cerebellum during postnatal development. At the light microscopic level, immunoreactivity for the GABAB1 and GABAB2 subunits was very prominent in the developing molecular layer, especially in Purkinje cells. Using double immunofluorescence, we demonstrated that GABAB1 was transiently expressed in glial cells. At the electron microscopic level, immunoreactivity for GABAB receptors was always detected both pre‐ and postsynaptically. Presynaptically, GABAB1 and GABAB2 were localized in the extrasynaptic membrane of parallel fibres at all ages, and only rarely in GABAergic axons. Postsynaptically, GABAB receptors were localized to the extrasynaptic and perisynaptic plasma membrane of Purkinje cell dendrites and spines throughout development. Quantitative analysis and three‐dimensional reconstructions further revealed a progressive developmental movement of the GABAB1 subunit on the surface of Purkinje cells from dendritic shafts to its final destination, the dendritic spines. Together, these results indicate that GABAB receptors undergo dynamic regulation during cerebellar development in association with the establishment and maturation of glutamatergic synapses to Purkinje cells.
Calcium permeability and flux through osmosensory transduction channels of isolated rat supraoptic nucleus neurons
Authors: Zhang Zizhen , Bourque Charles W. 
Published: March 2006

AbstractHypertonic stimuli delivered into the supraoptic nucleus provoke neuropeptide release from the somata of magnocellular neurosecretory cells (MNCs) in the presence of tetrodotoxin, suggesting that such stimuli can increase intracellular calcium concentration ([Ca2+]i) in the absence of action potentials. We therefore examined whether the stretch‐inhibited cation (SIC) channels of MNCs can mediate calcium influx. Whole‐cell recordings were made in MNCs isolated from the supraoptic nuclei of adult rats. Measurements of reversal potentials in different solutions revealed that the current induced by a suction‐evoked decrease in cell volume (ISIC) displays a selectivity sequence for monovalent cations of K+ > Cs+ > Na+ > NMDG+. The permeability of SIC channels to Ca2+, relative to Na+, was ∼ 5. In the presence of physiological concentrations of external Na+ and K+, the amplitude of inward ISIC was reduced dose‐dependently by external Ca2+ with an IC50 of 4.9 mm. This was not due to reduced suction‐evoked volume changes or to an accumulation of [Ca2+]i. Confocal imaging of cytoplasmic Calcium Green‐1 fluorescence revealed that activation of ISIC significantly increases [Ca2+]i in physiological solutions. This effect is absent in Ca2+‐free solution, or when Gd3+ (300 µm) is added to Ca2+‐containing solution. Part of this effect is inhibited in the presence of dantrolene (10 µm) and heparin (4 mg/mL), suggesting that release from intracellular Ca2+ stores participates in suction‐evoked Ca2+ signalling. These observations indicate that SIC channels are highly permeable to Ca2+, mediate significant Ca2+ entry and release of Ca2+ from internal stores under conditions when the volume of MNCs is decreased.
Mu‐opioid receptor cellular function in the nucleus accumbens is essential for hedonically driven eating
Authors: Ward Heather G. , Nicklous Danielle M. , Aloyo Vincent J. , Simansky Kenny J. 
Published: March 2006

AbstractAcute pharmacological studies have implicated mu‐opioid receptors (MORs) in the shell of the nucleus accumbens (NAC) in mediating responses for palatable food and other natural and drug‐induced rewards. However, the long‐term behavioral effects of inactivating signal transduction via accumbal MORs, as quantified by an anatomically defined loss of cellular activity, have never been analysed. We combined microinfusion of the irreversible MOR antagonist, β‐funaltrexamine (β‐FNA; 8.0 nmol/0.8 µL,n = 9; controls,n = 6) with mapping by [35S]GTPγS autoradiography to demonstrate an anatomically specific loss of the coupling of MORs to their G‐proteins in the dorsal caudomedial shell of the NAC in rabbits. β‐FNA did not alter the stimulated coupling of kappa‐opioid receptors. This selective blockade of the cellular function of MORs persistently decreased consumption of a palatable sucrose solution by 40% during a daily 4‐h test conducted 2, 3 and 4 days after infusion. β‐FNA did not alter body weight or 20‐h consumption of standard chow or water. In 10 different rabbits, infusion of the selective, competitive MOR antagonist, CTAP (D‐Phe‐Cys‐Tyr‐D‐Trp‐Arg‐Thr‐Pen‐Thr‐NH2) into the same locus produced a reversible decrease in sucrose consumption, with normal intakes returning on the next day. Together, these data appear to establish that MORs in this accumbal subregion support responding for orosensory reward. Overall, these results visualize a discrete brain locus where cellular actions of endogenous opioids mediate behaviors involved in self‐administration of foods and perhaps other hedonically valued substances, such as ethanol and drugs of abuse.
Brain regions underlying response inhibition and interference monitoring and suppression
Authors: Blasi Giuseppe , Goldberg Terry E. , Weickert Thomas , Das Saumitra , Kohn Philip , Zoltick Brad , Bertolino Alessandro , Callicott Joseph H. , Weinberger Daniel R. , Mattay Venkata S. 
Published: March 2006

AbstractResponse inhibition and interference monitoring and suppression are two important aspects of cognitive control. Previous functional imaging studies have suggested a common network of brain regions underlying these cognitive processes; the dorsolateral prefrontal cortex (DLPFC), the ventrolateral prefrontal cortex (VLPFC), the dorsal cingulate (dACC), and the parietal cortex (PC). The relative contribution of these regions to these cognitive subprocesses, however, has not been determined. Based on previous findings supporting a role for dACC in the monitoring of conflicting information within a stimulus, we hypothesized greater activity in this cortical region during interference monitoring and suppression relative to response inhibition. On the other hand, as response inhibition is characterized by differential cognitive processes such as control implementation, top down modulation of the response, expectancy, and inhibition of behavioural response, we hypothesized increased activity in the other cortical nodes of the cognitive control network relative to interference monitoring and suppression. To this end, we conducted an event‐related functional magnetic resonance imaging (fMRI) study in 57 healthy volunteers using a task preferentially involving either interference monitoring and suppression or response inhibition. Accuracy for response inhibition was lower than for interference monitoring and suppression. Imaging data showed activation in DLPFC, dACC, VLPFC, PC for both conditions. Comparisons between the two conditions indicated greater activation bilaterally in DLPFC, VLPFC and PC during response inhibition, and greater activation in the dACC during interference monitoring and suppression. These results extend previous findings by suggesting regional functional specialization within a cortical network supporting cognitive control.
Secretion of brain‐derived neurotrophic factor from brain microvascular endothelial cells
Authors: Wang Hong , Ward Nicole , Boswell Mark , Katz David M. 
Published: March 2006

AbstractThe cerebral microvasculature has recently been identified as a source of factors that can influence the generation and survival of neurons, including brain‐derived neurotrophic factor (BDNF). However, relatively little is known about signals that regulate secretion of endothelial cell derived BDNF. To approach this issue the present study examined BDNF secretion from brain endothelial cells in response to reduced oxygen availability (hypoxia), using the mouse brain microvascular endothelial cell line, bEnd.3. We found that exposure of bEnd.3 cells to either sustained or intermittent hypoxia (IH) stimulates BDNF expression and release and that IH is the more potent stimulus. IH‐induced BDNF release can be partially inhibited by either N‐acetyl‐l‐cysteine, a scavenger of reactive oxygen species, or by the stable superoxide dismutase mimetic manganese(III)tetrakis1‐methyl‐4‐pyridylporphyrin, indicating that oxyradical formation contributes to enhanced secretion of BDNF. In addition, we found that IH‐induced BDNF release requires Ca2+ mobilization from internal stores through ryanodine‐ and inositol (1,4,5‐triphosphate) IP3 receptors and is completely blocked by SKF 96365, a nonselective inhibitor of transient receptor potential (TRP) channels. These data demonstrate that bEnd.3 cells respond to oxidative stress by increasing BDNF secretion and, in addition, highlight TRP channels as potential therapeutic targets for enhancing BDNF availability from the cerebral microvasculature.
Diacylglycerol kinase ζ is involved in the process of cerebral infarction
Authors: Nakano Tomoyuki , Hozumi Yasukazu , Ali Hasmat , Saino‐Saito Sachiko , Kamii Hideyuki , Sato Shinya , Kayama Takamasa , Watanabe Masahiko , Kondo Hisatake , Goto Kaoru 
Published: March 2006

AbstractDiacylglycerol kinase (DGK) is an enzyme that phosphorylates a second messenger diacylglycerol (DG) and is involved in a variety of pathophysiological cellular responses. We have previously reported that DGKζ may be involved in the selective vulnerability of hippocampal CA1 neurons in transient forebrain ischemia. In this study we aimed to further elucidate functional implications of DGK isozymes in the cerebral cortex suffering from infarction using a focal ischemic model. In the early phase of 90 min of middle cerebral artery occlusion, DGKζ‐immunoreactivity is reduced rapidly in the nucleus of cortical neurons in the ischemic core, while DGKι and other neuronal proteins such as MAP‐2 and NeuN remain intact. This suggests that rapid disappearance of DGKζ in ischemic neurons is a quite early event precedent to neuronal degeneration in response to ischemia. Furthermore, in the late inflammatory phase of infarction DGKζ‐immunoreactivity is detected in non‐neuronal cells including factor VIII‐positive endothelial cells and ED‐1‐positive phagocytic cells. The present study suggests that DGKζ may play roles in various processes of ischemic brain damage including neuronal death and non‐neuronal inflammatory response.
Reduced hippocampal neurogenesis and number of hilar neurones in streptozotocin‐induced diabetic mice: reversion by antidepressant treatment
Authors: Beauquis Juan , Roig Paulina , Homo‐Delarche Françoise , De Nicola Alejandro , Saravia Flavia 
Published: March 2006

AbstractCerebral dysfunctions, including a high incidence of depression, are common findings in human type 1 diabetes mellitus. An association between depression and defective hippocampal neurogenesis has been proposed and, in rodents, antidepressant therapy restores neuronal proliferation in the dentate gyrus. Hippocampal neurogenesis is also deficient in diabetic mice, which led us to study whether the selective serotonin reuptake inhibitor fluoxetine influences cell proliferation in streptozotocin‐diabetic animals. Diabetic and control C57BL/6 mice received fluoxetine (10 mg/kg/day, i.p., 10 days) and dentate gyrus cell proliferation was measured after a single injection of 5‐bromo‐2′‐deoxyuridine (BrdU). Diabetic mice showed reduced cell proliferation. Fluoxetine treatment, although having no effect in controls, corrected this parameter in diabetic mice. The phenotype of newly generated cells was analysed by confocal microscopy after seven daily BrdU injections, using Tuj‐1/β‐III tubulin as a marker for immature neurones and glial fibrillary acidic protein for astrocytes. In controls, the proportion of Tuj‐1‐BrdU‐positive cells over total BrdU cells was ∼70%. In vehicle‐treated diabetic mice, immature neurones decreased to 56% and fluoxetine brought this proportion back to control values without affecting astrocytes. Therefore, fluoxetine preferentially increased the proliferation of cells with a neuronal phenotype. In addition, neurones were counted in the hilus of the dentate gyrus; a 30% decrease was found in diabetic mice compared with controls, whereas this neuronal loss was prevented by fluoxetine. In conclusion, fluoxetine treatment restored neuroplasticity‐related hippocampal alterations of diabetic mice. These findings may be potentially important to counteract diabetes‐associated depression in humans.