bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Social Model of Disability: A Philosophical Critique
Authors: Terzi Lorella 
Published: July 2004

abstract  Emerging from the political activism of disabled people's movements and mainly theorised by the scholar Michael Oliver, the social model of disability is central to current debates in Disability Studies as well as to related perspectives on inclusive education. This article presents a philosophical critique of the social model of disability and outlines some of its theoretical problems. It argues that in conceptualising disability as unilaterally socially caused, the social model presents a partial and, to a certain extent, flawed understanding of the relation between impairment, disability and society, thus setting a framework that needs clarifications and extensions and presents limits to the achievement of its own aim of inclusion. This article concludes by suggesting that, despite its theoretical limits, the social model acts as a powerful and important reminder to face issues of inclusion as fundamental, moral issues.
Developmental up‐regulation of MnSOD in rat oligodendrocytes confers protection against oxidative injury
Authors: Baud Olivier , Haynes Robin F. , Wang Hong , Folkerth Rebecca D. , Li Jianrong , Volpe Joseph J. , Rosenberg Paul A. 
Published: July 2004

AbstractPeriventricular leukomalacia, the predominant pathological lesion underlying cerebral palsy in premature infants, is thought to be the result of hypoxic–ischemic injury to the cerebral white matter. The main cell type injured is the developing oligodendrocyte (OL), which has been shown to be more sensitive than mature OLs to both excitotoxic and oxidative mechanisms of injury. A maturation dependence of OL vulnerability to cystine deprivation‐induced glutathione depletion has been previously demonstrated in culture. We hypothesized that mitochondria could be involved in this toxicity by generating superoxide and that increased superoxide dismutase (SOD) activity in mature OLs may account for their greater resistance. Cystine deprivation toxicity was found to be associated with mitochondrial dysfunction and intracellular superoxide accumulation in developing OLs. CuZnSOD protein expression and enzyme activity was similar along the OL lineage. In contrast, MnSOD was up‐regulated in mature OLs, as manifested by a 53% increase in its expression and a four‐fold increase in its activity. Overexpressing MnSOD in developing OLs was associated with a protective effect on mitochondrial membrane potential and a decrease in cell death induced by mild cystine deprivation. The greater challenge presented by total cystine deprivation was resistant to MnSOD overexpression and appeared to be related to hydrogen peroxide toxicity. These data suggest a primary involvement of superoxide in glutathione depletion toxicity in developing OLs, and suggest an important role for MnSOD in the resistance observed in mature OLs.
Apical endocytosis in outer hair cells of the mammalian cochlea
Authors: Griesinger C. B. , Richards C. D. , Ashmore J. F. 
Published: July 2004

AbstractOuter hair cells (OHCs), the sensory–motor cells of the mammalian cochlea, contain an endocytic tubulovesicular compartment below their apical stereocilia. We have used two‐photon imaging of FM1‐43 in the intact epithelium to show that these cells take up membrane in a Ca2+‐dependent manner from a distinct apical site. The uptake rate was 0.8 µm2/s and internalized membrane was trafficked rapidly to a compartment along the lateral wall and distinct intracellular compartments. Double labelling with FM1‐43 and DiOC6, an endoplasmic reticulum (ER) marker, showed that these compartments are part of the tubulovesicular endoplasmic reticulum of OHCs. Labelling with a lysosomal marker showed that OHC lysosomes are restricted to the apex. Using the protein marker wheat germ agglutinin (WGA‐FITC) we demonstrate that apical protein internalization and trafficking is about eight times slower than membrane internalization. Using double labelling with FM1‐43 and WGA‐FITC, we show that membrane and protein internalization are apically colocalized but that patterns of protein and membrane traffic differ. Protein was targeted only to the most apical third of the lateral wall. In control conditions, OHCs displayed only weak WGA‐FITC surface labelling at the site of endocytosis. Lowering the rate of apical endocytosis increased this surface signal. The results suggest that OHCs endocytose membrane and membrane proteins with a high turnover rate and that these cells may use apical endocytosis to sort proteins via an indirect pathway to the lateral membrane.
Brain hyperthermia induced by MDMA (‘ecstasy’): modulation by environmental conditions
Authors: Brown P. Leon , Kiyatkin Eugene A. 
Published: July 2004

AbstractDrugs of abuse, such as 3,4‐methylenedioxymethamphetamine (MDMA), often have more powerful effects during states of increased activation and under specific environmental conditions. Because hyperthermia is a major complication of MDMA use and a factor potentiating neurotoxicity, we examined the effects of this drug (9 mg/kg, sc; approximately one‐fifth of the known LD50 in rats) on brain [nucleus accumbens (Nacc) and hippocampus (Hippo)] and muscle (musculus temporalis) temperatures in male rats under conditions that either model human drug use (social interaction with female, warm temperature) or restrict heat dissipation from the brain (chronic occlusion of jugular veins). Under quiet resting conditions at 23 °C, MDMA induced a moderate but prolonged hyperthermia. Both NAcc and Hippo showed more rapid and stronger temperature increases than muscle, suggesting metabolic neural activation as a primary cause of brain hyperthermia. During social interaction with a female, brain hyperthermia induced by MDMA was significantly potentiated (+89%). Brain hyperthermia induced by MDMA was also strongly potentiated (+188%) in animals with chronically occluded jugular veins, suggesting impaired cerebral outflow enhances intrabrain heat accumulation. At 29 °C, MDMA pushed temperatures in the brain to its biological limits (>41 °C; +268%), resulting in fatalities in most (83%) tested animals. Therefore, by inducing metabolic brain activation and restricting heat dissipation, MDMA use under ‘party’ conditions may be much more dangerous than under standard laboratory conditions.
Dendritic excitability and localization of GABA‐mediated inhibition in spider mechanoreceptor neurons
Authors: Gingl Ewald , French Andrew S. , Panek Izabela , Meisner Shannon , Torkkeli Päivi H. 
Published: July 2004

AbstractGABAergic inhibition of mechanosensory afferent axon terminals is a widespread phenomenon in vertebrates and invertebrates. Spider mechanoreceptor neurons receive efferent innervation on their peripherally located axons, somata and sensory dendrites, and the dendrites have recently been shown to be excitable. Excitability of the spider sensory neurons is inhibited by muscimol and GABA, agonists of ionotropic GABA receptors. Here we asked where in the neurons this inhibition occurs. We found no evidence for inhibition of action potentials in the sensory dendrites, but axonal action potentials were rapidly suppressed by both agonists. Earlier work showed that metabotropic GABAB receptors are located on the dendrites and distal somata of the spider sensory neurons, where they modulate voltage‐activated conductances and may provide slower, prolonged inhibition. Therefore, GABA released from single peripheral efferents may activate both ionotropic and metabotropic receptor types, providing rapid suppression of axonal activity followed by slower inhibition that eventually prevents action potential initiation in the distal dendrites.
Synchronization of oxytocin neurons in suckled rats: possible role of bilateral innervation of hypothalamic supraoptic nuclei by single medullary neurons
Authors: Moos Françoise , Marganiec Arleta , Fontanaud Pierre , Guillou‐Duvoid Anne , Alonso Gérard 
Published: July 2004

AbstractWe have previously shown that oxytocin neurons located in the four hypothalamic magnocellular nuclei display synchronous bursts of action potentials before each milk ejection. The mechanisms involved in such a synchronization have, however, not yet been elucidated. In this study, we test the hypothesis of an extranuclear synchronization arising from a common extrahypothalamic input innervating bilateral magnocellular nuclei. First, two different retrograde tracers were injected into the right and left supraoptic nuclei of rats that were fixed 5–7 days later. Each tracer labelled numerous neurons in various brain regions ipsilateral or contralateral to the injection site, but colocalization of the two tracers within the same cell body could only be detected bilaterally in neurons in the ventromedial regions of the medulla oblongata. The axonal projections of these medullary neurons were then visualized by the unilateral microinjection of an anterograde tracer (BDA) within the ventromedial medulla oblongata. BDA‐labelled axons afferent to the hypothalamus were found to branch towards both supraoptic nuclei through medial portions of the optic chiasma. Finally, in anaesthetized lactating rats, surgical lesions were placed medially through the optic chiasma and the electrical activity of oxytocin neurons in bilateral supraoptic nuclei was pair‐recorded during suckling. The incidence of synchronous bursts in oxytocin neurons located within bilateral supraoptic nuclei were dramatically altered only when the medial portions of the optic chiasma were totally lesioned. Taken together, these data suggest that medullary neurons afferent to bilateral supraoptic nuclei are involved in the recruitment and synchronization of bursting in oxytocin neurons during suckling.
Abnormalities of presynaptic protein CDCrel‐1 in striatum of rats reared in social isolation: relevance to neural connectivity in schizophrenia
Authors: Barr Alasdair M. , Young Clint E. , Sawada Ken , Trimble William S. , Phillips Anthony G. , Honer William G. 
Published: July 2004

AbstractPost‐weaning social isolation‐rearing of rats leads to behavioural and neurochemical sequelae that model aspects of schizophrenia, and it may be useful to test hypotheses related to putative molecular mechanisms of the illness. In humans, the presynaptic protein CDCrel‐1 represents an interesting candidate molecule for the mechanism and aetiology of schizophrenia. CDCrel‐1 modulates dopamine neurotransmission, binds to the SNARE protein syntaxin and maps onto a region of chromosome 22q11 deleted in velo‐cardio–facial and DiGeorge syndromes, which are associated with increased prevalence of schizophrenia. Using the isolation‐rearing model, we measured immunoreactivity of the synaptic proteins CDCrel‐1, synaptophysin and syntaxin. Male, Sprague–Dawley rats were raised in groups or in isolation for 12 weeks from weaning. Synaptic protein immunoreactivities were measured in striatal and hippocampal homogenates, using a sensitive enzyme‐linked immunoadsorbent assay with monoclonal antibodies. Isolation‐rearing produced region‐ and protein‐specific effects. CDCrel‐1 immunoreactivity was significantly lower in the striatum and marginally higher in the hippocampus of isolation‐reared compared with socially reared animals. There were no statistically significant differences in synaptophysin immunoreactivity in either region. Confocal microscopy demonstrated a high degree of colocalization between the two presynaptic proteins. In striatum, a robust relationship between CDCrel‐1 and syntaxin immunoreactivities was observed in socially reared rats, this was lost in the isolation‐reared animals. Altered levels of the septin CDCrel‐1 in isolation‐reared rats may contribute to changes in neuronal connectivity and neurotransmission, and suggest a potential role for CDCrel‐1 in schizophrenia related to chromosome 22q11 deletion syndrome.
Amygdala central nucleus function is necessary for learning but not expression of conditioned visual orienting
Authors: McDannald Michael , Kerfoot Erin , Gallagher Michela , Holland Peter C. 
Published: July 2004

AbstractWhen exposed to pairings of a visual stimulus with food delivery, rats normally acquire both conditioned orienting responses directed toward the visual stimulus and conditioned food‐related responses. Consistent with the results of previous lesion studies, reversible inactivation of amygdala central nucleus function before each conditioning session prevented the acquisition of conditioned orienting responses, whereas food‐related behaviors were acquired normally. By contrast, neither inactivation nor neurotoxic lesions of central nucleus affected the expression of previously acquired conditioned orienting responses. Thus, the central nucleus is apparently not critical to the maintenance of information required for conditioned orienting, but instead is necessary for memory storage elsewhere. Specialized roles for components of a circuit for conditioned orienting, which includes the central nucleus, the substantia nigra, and dorsolateral striatum, are discussed.
Oral administration of desloratadine prior to sensitization prevents allergen‐induced airway inflammation and hyper‐reactivity in mice
Authors: Blümchen K. , Gerhold K. , Thorade I. , Seib C. , Wahn U. , Hamelmann E. 
Published: July 2004

SummaryBackground
Histamine‐1‐receptor (H1R)‐antagonists were shown to influence various immunological functions on different cell types and may thus be employed for immune‐modulating strategies for the prevention of primary immune responses.Objective
The aim of this study was to investigate the effects of an H1R‐antagonist on allergen‐induced sensitization, airway inflammation (AI) and airway hyper‐reactivity (AHR) in a murine model.Methods
BALB/c mice were systemically sensitized with ovalbumin (OVA) (six times, days 1–14) and challenged with aerosolized allergen (days 28–30). One day prior to the first and 2 h prior to every following sensitization, mice received either 1 or 0.01 μg of desloratadine (DL) or placebo per os.Results
Sensitization with OVA significantly increased specific and total IgE and IgG1 serum levels, as well as in vitro IL‐5 and IL‐4 production by spleen and peribronchial lymph node (PBLN) cells. Sensitized and challenged mice showed a marked eosinophilic infiltration in broncho‐alveolar lavage fluids and lung tissues, and developed in vivo AHR to inhaled methacholine. Oral treatment with DL prior to OVA sensitization significantly decreased production of OVA‐specific IgG1, as well as in vitro Th2‐cytokine production by spleen and PBLN cells, compared with OVA‐sensitized mice. Moreover, eosinophilic inflammation and development of in vivo AHR were significantly reduced in DL‐treated mice, compared with sensitized controls.Conclusion
Treatment with H1R‐anatagonist prior to and during sensitization suppressed allergen‐induced Th2 responses, as well as development of eosinophilic AI and AHR. This underscores an important immune modulating function of histamine, and implies a potential role of H1R‐anatagonists in preventive strategies against allergic diseases.
Kiwi fruit is a significant allergen and is associated with differing patterns of reactivity in children and adults
Authors: Lucas J. S. A. , Grimshaw K. E. C. , Collins K. , Warner J. O. , Hourihane J. O'B. 
Published: July 2004

SummaryBackground
Allergy to kiwi fruit appears increasingly common, but few studies have evaluated its clinical characteristics, or evaluated methods of investigating the allergy.Objective
To characterize the clinical characteristics of kiwi fruit allergy and to study the role of double‐blind placebo‐controlled food challenge (DBPCFC), skin tests and specific IgE in the diagnosis of this food allergy.Methods
Two‐hundred and seventy‐three subjects with a history suggestive of allergy to kiwi completed a questionnaire. Forty‐five were investigated by DBPCFC, prick‐to‐prick skin testing with fresh kiwi pulp, and specific IgE measurement. Nineteen subjects were also skin tested using a commercially available solution.Results
The most frequently reported symptoms were localized to the oral mucosa (65%), but severe symptoms (wheeze, cyanosis or collapse) were reported by 18% of subjects. Young children were significantly more likely than adults to react on their first known exposure (P<0.001), and to report severe symptoms (P=0.008). Twenty‐four of 45 subjects (53%) had allergy confirmed by DBPCFC. Prick‐to‐prick skin test with fresh kiwi was positive in 93% of subjects who had allergy confirmed by DBPCFC, and also in 55% of subjects with a negative food challenge. The commercial extract was significantly less sensitive, but with fewer false‐positive reactions. CAP sIgE was only positive in 54% of subjects who had a positive challenge.Conclusions
Kiwi fruit should be considered a significant food allergen, capable of causing severe reactions, particularly in young children. DBPCFC confirmed allergy to kiwi fruit in 53% of the subjects tested, who had a previous history suggestive of kiwi allergy. Skin testing with fresh fruit has good sensitivity (93%), but poor specificity (45%) in this population. CAP sIgE and a commercially available skin test solution were both much less sensitive (54%; 75%) but had better specificity (90%; 67%).
Asymptomatic atopy is associated with increased indoleamine 2,3‐dioxygenase activity and interleukin‐10 production during seasonal allergen exposure
Authors: Von Bubnoff D. , Fimmers R. , Bogdanow M. , Matz H. , Koch S. , Bieber T. 
Published: July 2004

SummaryBackground
Indoleamine 2,3‐dioxygenase (IDO) is a tryptophan (TRP)‐catabolizing enzyme with regulatory effects on T cells. T cell inhibition is achieved through both TRP depletion and TRP metabolite accumulation in specific local tissue microenvironments. The expression of IDO activity by different types of antigen‐presenting cells (APCs) has been shown to play a role in many instances of immunoregulation and tolerance induction. Induction of IDO after the engagement of the high‐affinity receptor for IgE, FcɛRI, on atopic monocytes has been suggested to regulate T cell responses in atopic disorders. Interleukin‐10 (IL‐10), a cytokine known for its down‐regulatory functions in the immune system, has recently been associated with the stable expression of IDO in mature tolerogenic dendritic cells.Objective
This study was devised to understand the role of systemic IDO and IL‐10 in the prevention of clinical apparent allergy.Methods
The concentration of TRP and the break‐down product kynurenine were measured by high‐performance liquid chromatography in‐ and off‐season in sera from patients with seasonal allergic rhinitis (n=12) and from clinically asymptomatic atopic patients sensitized to specific aeroallergens (n=12). Non‐atopic (NA) individuals (n=12) served as control. The concentration of plasma IL‐10 was determined in parallel from these donors by ELISA in‐ and off‐season.Results
In clinically unresponsive but aeroallergen‐sensitized atopic individuals significantly higher systemic activity of IDO and increased plasma IL‐10 levels were found during allergen exposure but not off‐season compared to symptomatic atopic individuals with allergic rhinitis and NA individuals.Conclusion
Enhanced systemic IDO activity as well as increased systemic levels of IL‐10 may contribute to the containment of allergic T cell responses and could be involved in the maintenance of a state of clinical unresponsiveness.
Interleukin‐5 receptors on human lung eosinophils after segmental allergen challenge
Authors: Julius P. , Hochheim D. , Böser K. , Schmidt S. , Myrtek D. , Bachert C. , Luttmann W. , Virchow J. C. 
Published: July 2004

SummaryBackground
IL‐5 is a specific cytokine for eosinophil accumulation, activation and prolongation of survival and can be recovered in elevated concentrations from the bronchoalveolar compartment in atopic asthma following allergen challenge.Objective
The action of IL‐5 is mediated via the specific IL‐5 receptor‐α (IL‐5Rα). Although in vitro data suggest that IL‐5R expression is regulated by cytokines such as IL‐3, IL‐5 and GM‐CSF, IL‐5R regulation in vivo and its kinetics following allergen provocation are incompletely understood.Methods
We investigated IL‐5R regulation in vivo following segmental allergen provocation (SAP) with an individually standardized dose of allergen in 12 patients with atopic asthma. Lavage was performed 10 min and 18 h (eight patients) and 10 min and 42 h (eight patients) after allergen challenge. In addition to differential cell counts, IL‐5Rα was measured by flow cytometry and IL‐5 concentrations in bronchoalveolar lavage (BAL) fluid were determined by ELISA.Results
IL‐5Rα expression decreased significantly on peripheral blood and on BAL eosinophils 18 and 42 h after SAP. In contrast, IL‐5 concentrations increased significantly in BAL fluid 18 and 42 h after SAP. In four and two patients, respectively, there were detectable IL‐5 concentrations in serum 18 or 42 h after allergen exposure.Conclusions
Although there was no correlation between IL‐5 concentrations and IL‐5Rα expression on eosinophils in BAL, our data support previous in vitro and in vivo findings of a negative feedback mechanism between IL‐5 concentrations and IL‐5Rα expression on eosinophils.
Nerve growth factor induces increased airway inflammation via a neuropeptide‐dependent mechanism in a transgenic animal model of allergic airway inflammation
Authors: Quarcoo D. , Schulte‐Herbrüggen O. , Lommatzsch M. , Schierhorn K. , Hoyle G.W. , Renz H. , Braun A. 
Published: July 2004

SummaryBackground
Nerve growth factor (NGF) exerts an important functional impact on the pathogenesis of allergic diseases. Data obtained in animal models of allergic bronchial asthma indicate that NGF alters sensory nerve function and promotes allergic inflammation, bronchial hyper‐reactivity, and airway obstruction.Objective
To further delineate the effects of NGF on airway inflammation, we employed a transgenic (tg) animal model of allergic inflammation and asthma.Methods
NGF‐tg mice, which overexpress NGF in Clara cells of the airways, were compared with wild‐type (wt) littermates regarding their ability to mount IgE‐related airway inflammatory responses. Mice were sensitized intraperitoneally to ovalbumin (OVA) and locally challenged via the airways according to established protocols.Results
NGF‐tg mice displayed enhanced levels of OVA‐specific IgE antibody titres after repeated OVA aerosol exposure. In the airways, increased numbers of eosinophils were detected. These results were confirmed to be NGF specific, because similar results were obtained following local application of NGF into the airways of wt mice. The effect of NGF was partly mediated via neuropeptides, as treatment of OVA‐sensitized NGF‐tg mice with the dual neurokinin (NK) receptor NK‐1/NK‐2 antagonist partly prevented enhanced airway inflammation.Conclusion
The present data indicate an important functional role of NGF in allergic airway inflammation and point to an involvement of tachykinins as mediators of NGF effects.