bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cranial optic nerve involvements in patients with severe COPD
Authors: ÖZGE Cengiz , ÖZGE Aynur , YILMAZ Ayça , YALÇINKAYA Deniz E. , ÇALIKOĞLU Mukadder 
Published: October 2005

Objective:  The relationship between neuropathy and increased morbidity in patients with COPD is clear, but few studies have assessed cranial neuropathies, especially optic nerve involvement, in COPD patients. We evaluated peripheral involvement of the optic nerve and determined factors influencing this condition in patients with severe COPD.Methodology:  Twenty‐eight patients, mean age 59.4 ± 9.4 years, diagnosed with severe stable COPD according to the GOLD criteria, and 20 age‐ and gender‐matched healthy individuals, mean age 55.6 ± 8.5 years, were included in the study. All subjects underwent visual evoked potential (VEP) assessment together with detailed clinical and laboratory examination to exclude concurrent risk factors for neuropathy.Results:  VEP assessment showed significant abnormalities in COPD patients (82.1%) (commonly amplitude abnormalities) when compared with healthy controls.Conclusions:  The optic nerve is often involved in patients with severe COPD, possibly as part of a polyneuropathy, and this is related to acidosis, hypercarbia and airway obstruction, independent of disease duration, smoking and age. These results should be taken into consideration when determining management strategies for these patients.
Ethics committee reviews and mutual acceptance: a pilot study
Authors: Rosenthal M. A. , Sarson‐Lawrence M. , Alt C. , Arkell K. , Dodds M. 
Published: October 2005

Abstract Aims:  To develop a human research ethics committee (HREC) mutual acceptance (MA) model, based on the National Health and Medical Research Council's guidelines. The MA model aims to facilitate aspects of multicentre research and decrease the time taken to finalise the HREC review process.Methods:  Four HREC (The Alfred Hospital, Austin Health, Peter MacCallum Cancer Centre and Melbourne Health) agreed to participate in a 13‐month pilot project to evaluate the MA model. Evaluation included times from submission to approval and stakeholder surveys.Results:  Seventeen consecutive studies were submitted to the MA pilot project. Stakeholders agreed that the MA model was efficient and effective and that submission and review processes had improved, with a demonstrable reduction in the levels of duplication. There was a 27% improvement in approval times for multicentre studies.Conclusions:  Our (MA) model resulted in clear improvements in HREC processes and timelines. Stakeholder acceptance was high. This model provides a framework for a broader program of MA. (Intern Med J 2005; 35: 650–654)
‘On being both professional and human’: one woman's journey
Authors: With An Introductory Note By P.Komesaroff Anonymous 
Published: October 2005

Introductory note by Paul Komesaroff The following reflection was written by the wife of a patient who died in the intensive care unit of a large public hospital after a stay of nearly 5 months. The author has chosen to remain anonymous to protect her privacy.The article is presented because we believe it offers deep insights into the experiences of relatives and other carers of patients with serious illnesses. Caring for carers or relatives is usually considered to lie outside the boundaries of the doctor–patient relationship. Although meticulous attention is often given to providing information and consulting about medical decisions, clinicians rarely consider that they have a responsibility to those closest to the patient, even though it is these people who will carry the burden of the experiences of the illnesses of their loved ones, perhaps for many decades.Clinical communication is concerned not only with the transmission of information. It is not a purely formal process of conveying facts or data. It is also about engaging another person in a dialogue about fears, uncertainties and hopes and, where appropriate, negotiating with him or her about priorities, goals and values. In many cases the perceptions of the health‐care team are very different from those of patients and their relatives; accordingly, there may be no way of avoiding the need for such dialogue and negotiation.This article draws attention to the importance of ‘recognition’ as an ethical act: recognition of the roles carers and relatives play in the lives of their loved ones, and of the pain and loss they themselves are suffering. When a physician cares for a patient it is not just an isolated individual who is being treated but the full, complex network of social relations in which he or she is embedded.Recognition also entails acknowledgment of error or of bad outcomes. In the world of someone undergoing bereavement, such acknowledgment might acquire great intensity. Small gestures can make a big impact. Where appropriate – for example, in the case of an adverse outcome – a formal apology, independent of any admissions of legal liability, may play a powerful therapeutic role. This article emphasises the fundamental healing potential of the apology.The voices of patients and relatives must be acknowledged and interpreted in their proper contexts. It is not suggested here that these expressions are of greater validity or authenticity than the perspective of the medical team. Nor should they be regarded as demonstrating the existence of a pathology within the psyches of patients and relatives that can only be understood through the instrumental discourses of medicine1. Rather, as this case demonstrates, patient narratives constitute a supplement to the medical ones, but also offer a commentary on them and provide insights from which clinical practice can be enriched and refined.
Relaxin receptor activation in the basolateral amygdala impairs memory consolidation
Authors: Ma Sherie , Roozendaal Benno , Burazin Tanya C. D. , Tregear Geoffrey W. , McGaugh James L. , Gundlach Andrew L. 
Published: October 2005

AbstractThe peptide‐hormone relaxin has well‐established actions in male and female reproductive tracts, and has functional effects in circumventricular regions of brain involved in neurohormonal secretion. In the current study, we initially mapped the distribution of mRNA encoding the relaxin receptor − leucine‐rich repeat‐containing G‐protein‐coupled receptor 7 (LGR7)‐ and [33P]‐human relaxin‐binding sites in extra‐hypothalamic sites of male Sprague–Dawley rats. The basolateral amygdala (BLA) expressed high levels of LGR7 mRNA and relaxin‐binding sites and, although relaxin peptide was not detected in the BLA, several brain regions that send projections to the BLA were found to contain relaxin‐expressing neurons. As it is well established that the BLA is involved in regulating the consolidation of memory for emotionally arousing experiences, we investigated whether activation of LGR7 in the BLA modulated memory consolidation for aversively motivated inhibitory avoidance training. Bilateral infusions of human relaxin (10–200 ng in 0.2 µL) into the BLA immediately after inhibitory avoidance training impaired 48‐h retention performance in a dose‐dependent manner. Delayed infusions of relaxin into the BLA 3 h after training were ineffective, indicating that the retention impairment was due to influences on memory consolidation. Post‐training infusions of relaxin into the adjacent central amygdala, which is devoid of LGR7, did not impair retention. These findings suggest a novel function for endogenous relaxin–LGR7 signalling in rat brain involving regulation of memory consolidation.
Reduced extracellular space in the brain of tenascin‐R‐ and HNK‐1‐sulphotransferase deficient mice
Authors: Syková Eva , Voříšek Ivan , Mazel Tomáš , Antonova Tatiana , Schachner Melitta 
Published: October 2005

AbstractTenascin‐R (TN‐R), a large extracellular glycoprotein, is an important component of the adult brain's extracellular matrix (ECM); tenascin‐C (TN‐C) is expressed mainly during early development, while human natural killer 1 (HNK‐1) is a sulphated carbohydrate epitope that attaches to these molecules, modifying their adhesive properties. To assess their influence on extracellular space (ECS) volume and geometry, we used the real‐time iontophoretic method to measure ECS volume fraction α and tortuosity λ, and diffusion‐weighted magnetic resonance imaging (MRI) to measure the apparent diffusion coefficient of water (ADCW). Measurements were performed in vivo in the cortex and CA1 hippocampal region of TN‐R‐, TN‐C‐ and HNK‐1 sulphotransferase (ST)‐deficient adult mice and their wild‐type littermate controls. In both cortex and hippocampus, the lack of TN‐R or HNK‐1 sulphotransferase resulted in a significant decrease in α and λ. Compared with controls, α in TN‐R–/– and ST–/– mice decreased by 22–26% and 9–15%, respectively. MRI measurements revealed a decreased ADCW in the cortex, hippocampus and thalamus. ADCW reflected the changes in α; the decrease in λ indicated fewer diffusion obstacles in the ECS, presumably due to a decreased macromolecular content. No significant changes were found in TN‐C–/– animals. We conclude that in TN‐R–/– and ST–/– mice, which show morphological, electrophysiological and behavioural abnormalities, the ECS is reduced and its geometry altered. TN‐R, as an important component of the ECM, appears to maintain an optimal distance between cells. The altered diffusion of neuroactive substances in the brain will inevitably affect extrasynaptic transmission, neuron–glia interactions and synaptic efficacy.
Sleep deprivation suppresses neurogenesis in the adult hippocampus of rats
Authors: Guzman‐Marin Ruben , Suntsova Natalia , Methippara Melvi , Greiffenstein Richard , Szymusiak Ronald , McGinty Dennis 
Published: October 2005

AbstractWe reported previously that 96 h of sleep deprivation (SD) reduced cell proliferation in the dentate gyrus (DG) of the hippocampus in adult rats. We now report that SD reduces the number of new cells expressing a mature neuronal marker, neuronal nuclear antigen (NeuN). Rats were sleep‐deprived for 96 h, using an intermittent treadmill system. Total sleep time was reduced to 6.9% by this method in SD animals, but total treadmill movement was equated in SD and treadmill control (CT) groups. Rats were allowed to survive for 3 weeks after 5‐bromo‐2‐deoxyuridine (BrdU) injection. The phenotype of BrdU‐positive cells in the DG was assessed by immunofluorescence and confocal microscopy. After 3 weeks the number of BrdU‐positive cells was reduced by 39.6% in the SD group compared with the CT. The percentage of cells that co‐localized BrdU and NeuN was also lower in the SD group (SD: 46.6 ± 1.8% vs. CT: 71.9 ± 2.1, P < 0.001). The percentages of BrdU‐labeled cells co‐expressing markers of immature neuronal (DCX) or glial (S100‐β) cells were not different in SD and CT groups. Thus, SD reduces neurogenesis in the DG by affecting both total proliferation and the percentage of cells expressing a mature neuronal phenotype. We hypothesize that sleep provides anabolic or signaling support for proliferation and cell fate determination.
Involvement of spinal cord nuclear factor κB activation in rat models of proinflammatory cytokine‐mediated pain facilitation
Authors: Ledeboer Annemarie , Gamanos Michael , Lai Wenmin , Martin David , Maier Steven F. , Watkins Linda R. , Quan Ning 
Published: October 2005

AbstractProinflammatory cytokines, such as interleukin‐1β and tumour necrosis factor‐α, are released by activated glial cells in the spinal cord and play a major role in pain facilitation. These cytokines exert their actions, at least partially, through the activation of the transcription factor, nuclear factor κB (NF‐κB). In turn, NF‐κB regulates the transcription of many inflammatory mediators, including cytokines. We have previously shown that intrathecal injection of the human immunodeficiency virus‐1 (HIV‐1) envelope glycoprotein, gp120, induces mechanical allodynia via the release of proinflammatory cytokines. Here, we investigated whether NF‐κB is involved in gp120‐induced pain behaviour in Sprague–Dawley rats. Intrathecal administration of NF‐κB inhibitors, pyrrolidinedithiocarbamate (PDTC) and SN50, prior to gp120 partially attenuated gp120‐induced allodynia. In addition, PDTC delayed and reversed allodynia in a model of neuropathic pain induced by sciatic nerve inflammation. These observations suggest that intrathecal gp120 may lead to activation of NF‐κB within the spinal cord. To reveal NF‐κB activation, we assessed inhibitory factor κBα (IκBα) mRNA expression by in situ hybridization, as NF‐κB activation up‐regulates IκBα gene expression as part of an autoregulatory feedback loop. No or low levels of IκBα mRNA were detected in the lumbar spinal cord of vehicle‐injected rats, whereas IκBα mRNA expression was markedly induced in the spinal cord following intrathecal gp120 in predominantly astrocytes and endothelial cells. Moreover, IκBα mRNA expression positively correlated with proinflammatory cytokine protein levels in lumbosacral cerebrospinal fluid. Together, these results demonstrate that spinal cord NF‐κB activation is involved, at least in part, in exaggerated pain states.
Distinct and overlapping fMRI activation networks for processing of novel identities and locations of objects
Authors: Pihlajamäki Maija , Tanila Heikki , Könönen Mervi , Hänninen Tuomo , Aronen Hannu J. , Soininen Hilkka 
Published: October 2005

AbstractThe ventral visual stream processes information about the identity of objects (‘what’), whereas the dorsal stream processes the spatial locations of objects (‘where’). There is a corresponding, although disputed, distinction for the ventrolateral and dorsolateral prefrontal areas. Furthermore, there seems to be a distinction between the anterior and posterior medial temporal lobe (MTL) structures in the processing of novel items and new spatial arrangements, respectively. Functional differentiation of the intermediary mid‐line cortical and temporal neocortical structures that communicate with the occipitotemporal, occipitoparietal, prefrontal, and MTL structures, however, is unclear. Therefore, in the present functional magnetic resonance imaging (fMRI) study, we examined whether the distinction among the MTL structures extends to these closely connected cortical areas. The most striking difference in the fMRI responses during visual presentation of changes in either items or their locations was the bilateral activation of the temporal lobe and ventrolateral prefrontal cortical areas for novel object identification in contrast to wide parietal and dorsolateral prefrontal activation for the novel locations of objects. An anterior‐posterior distinction of fMRI responses similar to the MTL was observed in the cingulate/retrosplenial, and superior and middle temporal cortices. In addition to the distinct areas of activation, certain frontal, parietal, and temporo‐occipital areas responded to both object and spatial novelty, suggesting a common attentional network for both types of changes in the visual environment. These findings offer new insights to the functional roles and intrinsic specialization of the cingulate/retrosplenial, and lateral temporal cortical areas in visuospatial cognition.
Eph/ephrin expression in the adult rat visual system following localized retinal lesions: localized and transneuronal up‐regulation in the retina and superior colliculus
Authors: Rodger J. , Symonds A. C. E. , Springbett J. , Shen W‐Y. , Bartlett C. A. , Rakoczy P. E. , Beazley L. D. , Dunlop S. A. 
Published: October 2005

AbstractFollowing unilateral optic nerve section in adult PVG hooded rat, the axon guidance cue ephrin‐A2 is up‐regulated in caudal but not rostral superior colliculus (SC) and the EphA5 receptor is down‐regulated in axotomised retinal ganglion cells (RGCs). Changes occur bilaterally despite the retino‐collicular projection being mostly crossed. Here we investigate the dynamics of Eph/ephrin expression using in situ hybridization and semi‐quantitative immunohistochemistry after localized retinal lesions. Unilateral krypton laser lesions to dorso‐nasal retina ablated contralaterally projecting RGCs (DN group); ventro‐temporal lesions ablated contralaterally and ipsilaterally projecting RGCs (VT group). Lesions of the entire retina served as controls (Total group). Results are compared to normal animals in which tectal ephrin‐A2 and retinal EphA5 are expressed, respectively, as shallow ascending rostro‐caudal and naso‐temporal gradients. In both SCs of DN and Total groups, tectal ephrin‐A2 was up‐regulated caudally; in the VT group, expression remained normal bilaterally. Unilateral collicular ablation indicated that bilateral changes in ephrin‐A2 expression are mediated via intercollicular pathways. EphA5 expression in the VT group was elevated in the intact nasal region of experimental retinae. For each experimental group, EphA5 expression was also elevated in nasal retina of the opposite eye, resulting in uniform expression across the naso‐temporal axis. Up‐regulation of ephrin‐A2 in caudal, but not rostral, SC suggests the enhancement of developmental positional information as a result of injury. Bilateral increases in retinal EphA5 expression demonstrate that signals for up‐regulation operate interocularly. The study demonstrates that signals regulating guidance cue expression are both localized and relayed transneuronally.
The T1 domain of Kv1.3 mediates intracellular targeting to axons
Authors: Rivera Jacqueline F. , Chu Po‐Ju , Arnold Don B. 
Published: October 2005

AbstractShaker K+ channels play an important role in modulating electrical excitability of axons. Recent work has demonstrated that the T1 tetramerization domain of Kv1.2 is both necessary and sufficient for targeting of the channel to the axonal surface [Gu, C., Jan, Y.N. & Jan, L.Y. (2003)Science,301, 646–649]. Here we use a related channel, Kv1.3, as a model to investigate cellular mechanisms that mediate axonal targeting. We show that the T1 domain of Kv1.3 is necessary and sufficient to mediate targeting of the channel to the axonal surface in pyramidal neurons in slices of cortex from neonatal rat. The T1 domain is also sufficient to cause preferential axonal localization of intracellular protein, which indicates that the domain probably does not work through compartment‐specific endocytosis or compartment‐specific vesicle docking. To determine whether the T1 domain mediates axonal trafficking of transport vesicles, we compared the trafficking of vesicles containing green fluorescent protein‐labelled transferrin receptor with those containing the same protein fused with the T1 domain in living cortical neurons. Vesicles containing the wild‐type transferrin receptor did not traffic to the axon, in accord with previously published results; however, those containing the transferrin receptor fused to T1 did traffic to the axon. These results are consistent with the T1 domain of Kv1.3 mediating axonal targeting by causing transport vesicles to traffic to axons and they represent the first evidence that such a mechanism might underlie axonal targeting.
Disruption of the neurogenic potential of the dentate gyrus in a mouse model of temporal lobe epilepsy with focal seizures
Authors: Kralic Jason E. , Ledergerber Debora A. , Fritschy Jean‐Marc 
Published: October 2005

AbstractAdult hippocampal neurogenesis is enhanced in response to multiple stimuli including seizures. However, the relationship between neurogenesis and the development of temporal lobe epilepsy (TLE) remains unclear. Unilateral intrahippocampal injection of kainate in adult mice models the morphological characteristics (e.g. neuronal loss, gliosis, granule cell dispersion and hypertrophy) and occurrence of chronic, spontaneous recurrent partial seizures observed in human TLE. We investigated the influence of a kainate‐induced epileptogenic focus on hippocampal neurogenesis, comparing neural stem cell proliferation following status epilepticus and spontaneous recurrent partial seizures. Cell proliferation in the subgranular zone was transiently increased bilaterally after kainate treatment. As a result, neurogenesis was stimulated in the contralateral dentate gyrus. In contrast, the epileptic hippocampus exhibited a strongly reduced neurogenic potential, even after onset of spontaneous recurrent partial seizures, possibly due to an alteration of the neurogenic niche in the subgranular zone. These results show that neurogenesis does not contribute to the formation of the epileptic focus and may be affected when dispersion of dentate gyrus granule cells occurs. Therefore, in patients with TLE, hippocampal sclerosis and granule cell dispersion may play a significant role in disrupting the potential for hippocampal neurogenesis.
ATF3 expression precedes death of spinal motoneurons in amyotrophic lateral sclerosis‐SOD1 transgenic mice and correlates with c‐Jun phosphorylation, CHOP expression, somato‐dendritic ubiquitination and Golgi fragmentation
Authors: Vlug Angela S. , Teuling Eva , Haasdijk Elize D. , French Pim , Hoogenraad Casper C. , Jaarsma Dick 
Published: October 2005

AbstractTo obtain insight into the morphological and molecular correlates of motoneuron degeneration in amyotrophic lateral sclerosis (ALS) mice that express G93A mutant superoxide dismutase (SOD)1 (G93A mice), we have mapped and characterized ‘sick’ motoneurons labelled by the ‘stress transcription factors’ ATF3 and phospho‐c‐Jun. Immunocytochemistry and in situ hybridization showed that a subset of motoneurons express ATF3 from a relatively early phase of disease before the onset of active caspase 3 expression and motoneuron loss. The highest number of ATF3‐expressing motoneurons occurred at symptom onset. The onset of ATF3 expression correlated with the appearance of ubiquitinated neurites. Confocal double‐labelling immunofluorescence showed that all ATF3‐positive motoneurons were immunoreactive for phosphorylated c‐Jun. Furthermore, the majority of ATF3 and phospho‐c‐Jun‐positive motoneurons were also immunoreactive for CHOP (GADD153) and showed Golgi fragmentation. A subset of ATF3 and phosphorylated c‐Jun‐immunoreactive motoneurons showed an abnormal appearance characterized by a number of distinctive features, including an eccentric flattened nucleus, perikaryal accumulation of ubiquitin immunoreactivity, juxta‐nuclear accumulation of the Golgi apparatus and the endoplasmic reticulum, and intense Hsp70 immunoreactivity. These abnormal cells were not immunoreactive for active caspase 3. We conclude that motoneurons in ALS‐SOD1 mice prior to their death and disappearance experience a prolonged sick phase, characterized by the gradual accumulation of ubiquitinated material first in the neurites and subsequently the cell body.
The spatial filtering properties of local edge detectors and brisk–sustained retinal ganglion cells
Authors: Zeck Günther M. , Xiao Quan , Masland Richard H. 
Published: October 2005

AbstractWe compared image computation in the rabbit retina by two different cell types: the so‐called ‘local edge detecting’ ganglion cells and the well‐known brisk–sustained ganglion cells. From both anatomical and physiological evidence, these cells are present in nearly equal numbers and thus overlap to sample the same regions of visual space. We recorded simultaneously from overlapping cells on a dense microelectrode array. The results were analysed using an anatomically realistic simulation of the retina's processing levels. The ‘local edge detecting’ cell was found to be tuned to higher spatial frequencies and to have a narrower spatial frequency bandpass than the brisk–sustained cells. Simulation revealed that this is due primarily to the ‘zero‐crossing’ detector implied by the definition of the local edge detector. The outputs of the simulations in response to complex images were analysed quantitatively. The results showed the population of local edge detectors to transmit a sparser code than the brisk–sustained cells.