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1

Kaminska, Anna. "Réponses corticales aux stimulations sensorielles étudiées par électroencéphalographie chez le nouveau-né de 30 semaines d'âge gestationnel jusqu'au terme". Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCB110.

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Les populations neuronales ont la capacité de s’organiser en réseaux qui produisent spontanément différents patterns d’activité électrique coordonnée. Au travers de leur activité synchrone, les réseaux immatures combinent les informations génétiques et les influences environnementales et contrôlent plusieurs processus neuro-développementaux dont la plasticité synaptique. Pendant le développement prénatal et post-natal précoce, ces activités électriques synchrones peuvent être générées au sein des cortex sensoriels eux-mêmes, des structures sous-corticales ou être évoquées par l’activité des organes sensoriels, elle-même spontanée ou provoquée par les stimuli sensoriels. Dans des travaux antérieurs, nous avons montré qu’un pattern EEG typique du prématuré, le « Delta-brush » (DB), qui associe une onde lente et des oscillations rapides, pouvait être évoqué dans les cortex primaires sensori-moteur, visuel et auditif par les mouvements spontanés et par les stimuli sensoriels correspondants. L’objectif de la présente étude, dédiée aux réponses corticales aux stimuli auditifs (click), était de préciser les caractéristiques spatio-temporelles des DBs évoqués ainsi que leur rapport avec des potentiels évoqués auditifs corticaux. Pour cela, les enregistrements EEG ont été réalisés en haute résolution (32 électrodes) chez 30 nouveau-nés prématurés de 30 à 38 semaines d’âge gestationnel sans risque neurologique et la position des électrodes a été recalée sur des IRM 3D acquises chez d’autres prématurés représentatifs des âges étudiés. L’analyse de population a montré une augmentation significative de la puissance spectrale après le stimulus dans toutes les bandes de fréquence allant du delta à gamma et située au niveau de la partie moyenne et postérieure du lobe temporal. Ces réponses du cortex temporal avaient une prédominance droite, étaient plus amples dans le sommeil calme et diminuaient en puissance avec l’âge. Le moyennage des réponses EEG a révélé que la composante lente du DB était une onde lente négative de grande amplitude qui culminait dans les régions temporales moyenne et postérieure à environ 550 et 700 ms respectivement. L’analyse temps-fréquence a confirmé la présence d’oscillations rapides dont les oscillations gamma, à partir du pic de l’onde lente et cohabitant avec cette dernière durant environ 700 ms. Ces résultats suggèrent que le DB évoqué par les stimuli auditifs correspond en fait à la composante lente tardive du potentiel évoqué auditif cortical du prématuré et qu’il regroupe des oscillations dans toutes les bandes de fréquence, gamma y compris, fréquence identifiée ici pour la première fois en réponse à un stimulus sensoriel chez le prématuré humain. Nous avons obtenu des résultats préliminaires similaires aussi dans une autre modalité sensorielle ; l’activité oscillatoire du DB évoqué contribue donc probablement à la maturation des cartes corticales et représente un biomarqueur potentiel du fonctionnement normal des cortex sensoriels chez le prématuré
At the early developmental stages, during the third trimester of gestation in humans and the first post-natal weeks in rodents, sensory neocortical areas reveal similar patterns of spontaneous correlated neuronal activity. In vitro and in vivo experiments indicate that these spontaneous activities are generated from neuronal networks in the cerebral cortex, in subcortical structures or in the sensory periphery (retina, limb jerks, whiskers). Spontaneous, periphery-driven and also sensory evoked activity is relayed to the developing cerebral cortex via the thalamus and the neocortical subplate, which amplifies the afferent sensory input. The patterns of sensory evoked activity were extensively studied in rodents, but in humans their spatiotemporal dynamics still remain elusive. In humans this developmental process happens during the second half of gestation: the major growing afferents from the thalamus spread within the transient subplate zone, relocate in the cortical plate, and form functional synapses with both transient and permanent neuronal populations. Characteristic immature activity patterns of “delta-brushes” (DBs) have been reported in the preterm temporal cortex following auditory stimuli. However, the spatiotemporal dynamics of these auditory-evoked DBs remain elusive. Here, we explored the electrophysiological responses evoked by click stimuli using 32-electrode EEG recordings in thirty premature infants from 30 to 38 postmenstrual weeks (PMW) of age. Electrodes position was digitalized and registered to 3D reconstructions of preterm heads and brains computed from MRI images of other age-matched groups. Population power spectrum analysis within the 2 seconds after stimulation revealed significant increase in all frequency bands from delta to gamma, located on the middle and posterior temporal regions with a right predominance and higher power increase in the quiet sleep. Time-frequency wavelet analysis also showed fast oscillations including gamma that begin at the peak of the delta waves and co-occur with it during a period of around 700 ms. Power of auditory evoked responses significantly decreased from 30 to 38 WPM in delta to alpha bands. These are the first report of gamma oscillations in preterm sensory evoked responses. Furthermore, average cortical auditory evoked potentials (CAEP) (processed with a mean reference and a 0.16 Hz high-pass filter) revealed high amplitude delta negative waves peaking successively from the middle to posterior temporal regions at around 550 and 700 ms. Altogether these results suggest that the auditory-evoked DBs in premature infants are a slow late component of the CAEP covering temporal regions and grouping fast oscillations notably gamma oscillations
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2

Aguilera, Matthieu. "The light at the end of the tunnel : study of early-stage brain dynamics alterations in Alzheimer’s disease and beneficial effects of light stimulation in the AppNL-F/MAPT mouse model". Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ066.

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La maladie d’Alzheimer (MA), première cause de démence dans le monde, reste un défi majeur en raison de son diagnostic tardif et de l’absence de traitements efficaces. Alors que le diagnostic actuel repose sur la détection à travers des méthodes invasives de marqueurs pathologiques classiques tels que les plaques amyloïdes après l'apparition des symptômes cognitifs, de nombreuses études suggèrent que les changements pathologiques débutent des décennies avant ces manifestations cliniques. Le bon fonctionnement cérébral dépend d’une activité dynamique complexe, permettant des transitions flexibles entre différents réseaux fonctionnels. Ces dynamiques cérébrales, observables par EEG ou IRM fonctionnel, sont altérées dans plusieurs troubles neurologiques, dont la MA. Compte tenu de l’importance de la dynamique cérébrale pour les fonctions cognitives, une approche thérapeutique récente, appelée GENUS, utilise des stimulations sensorielles à 40 Hz pour moduler les oscillations neuronales. Cette approche a des effets prometteurs dans la MA malgré des mécanismes encore mal connus. En utilisant des enregistrements EEG haute densité dans un modèle préclinique de la MA, nous avons démontré des altérations de la dynamique cérébrale avant la formation des plaques amyloïdes, avec une fluidité réduite durant l’éveil associée à des déficits cognitifs subtils. Deux semaines de GENUS ont permis de restaurer à la fois les performances mnésiques et la dynamique cérébrale avant la formation des plaques amyloïdes, suggérant des bénéfices au-delà des effets du GENUS précédemment rapportés sur la pathologie amyloïde. Ce travail de thèse propose ainsi un outil de diagnostic précoce prometteur basé sur des mesures EEG non invasives, et démontre l’efficacité d’une intervention thérapeutique simple, facilement applicable en clinique, offrant de nouvelles perspectives pour la détection et le traitement précoces de la MA
Alzheimer's disease (AD), the leading cause of dementia worldwide, remains a major healthcare challenge due to late diagnosis and lack of effective treatments. While current diagnosis relies on invasive detection of classic amyloid and tau pathological hallmarks after cognitive symptoms appear, mounting evidence suggests that pathological changes begin decades before these clinical manifestations. Proper brain function depends on complex dynamic activity, allowing flexible transitions between different functional networks. These brain dynamics, assessable through EEG or functional MRI, are altered in various neurological conditions, including AD. Given their importance in cognitive function, a recent therapeutic approach called GENUS uses 40Hz sensory stimulation to modulate neural oscillations, showing promising effects in AD despite debated mechanisms. Using high-density EEG recordings in a preclinical AD mouse model, we demonstrated altered brain dynamics before amyloid plaque formation, showing reduced fluidity during wakefulness concurrent with subtle cognitive deficits. Two weeks of visual GENUS restored both memory performance and brain dynamics before amyloid plaque formation, suggesting benefits beyond previously reported effects on amyloid pathology. This thesis work presents both a promising early diagnostic tool based on non-invasive EEG measurements and demonstrates the efficacy of a simple therapeutic intervention readily implementable in clinical settings, offering new perspectives for early AD detection and treatment
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3

Martorell, Anthony J. Ph D. (Anthony James) Massachusetts Institute of Technology. "Multi-sensory gamma stimulation ameliorates Alzheimer's-associated pathology and improves cognition". Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/132749.

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Abstract (sommario):
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, June, 2019
Cataloged from the PDF version of thesis. Page 123 blank.
Includes bibliographical references (pages 115-122).
Changes in gamma activity (30-90 Hz) have been observed in humans and animal-models of Alzheimer's disease (AD). Examining the relationship between gamma oscillations and disease pathology is a significant problem in neuroscience. Recent work using a non-invasive light flicker at 40 Hz, termed Gamma ENtrainment Using Sensory stimulus, or 'GENUS', was shown to impact pathology in the visual cortex of AD-mouse models. However, it is not known whether other sensory modalities at 40 Hz can change pathology in higher order brain regions, or affect cognition, in AD-like animal models. In this thesis, I combine in vivo electrophysiology, biochemical and imaging techniques, and behavioral assays to understand the effects of multi-sensory gamma stimulation in AD-like animals. I first show that auditory tone stimulation at 40 Hz (auditory GENUS) can drive gamma frequency neural activity in auditory cortex (AC) and hippocampal CA1. I then demonstrate that seven days of auditory GENUS results in improved spatial and recognition memory and reduced amyloid load in AC and hippocampus of 5XFAD mice. These changes in activation responses were evident in microglia, astrocytes, and vasculature. Additionally, auditory GENUS reduced phosphorylated tau in the tau P301S model. Finally, I demonstrate that combined auditory and visual GENUS, but not either alone, decreases amyloid and produces a microglial-clustering response in the medial prefrontal cortex. Whole brain analysis using SHIELD processing revealed widespread reduction of amyloid plaques throughout neocortex after multi-sensory GENUS. These findings suggest that GENUS can be achieved through multiple sensory modalities with wide-ranging effects across multiple brain areas to improve cognitive function.
by Anthony J. Martorell.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences
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4

Peng, Peijing. "Interaction of alpha-gamma-MSH analogues with MC1, MC3 and MC4 melanocortin receptors". Thesis, University of Bath, 1997. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338413.

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5

Weigt, Henning. "Induktion einer TH1-Reaktion nach Stimulation von dendritischen Zellen mit MALP-2 und IFN-[gamma] [IFN-gamma] in einem In-vitro-Allergiemodell". [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=96929235X.

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6

Goodwin, David G. "Age and Sex Related Behavioral Changes in Mice Congenitally Infected with Toxoplasma gondii: Role of dopamine and other neurotransmitters in the genesis of behavioral changes due to congenital infection and attempted amelioration with interferon gamma". Diss., Virginia Tech, 2011. http://hdl.handle.net/10919/28412.

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Evidence suggests that the neurotropic parasite Toxoplasma gondii may play a role in the development of cognitive impairments. My hypothesis was that congenital exposure to T. gondii would lead to detectable age and sex related differences in behavior and neurotransmitter levels in mice. The neurotransmitter dopamine and commonly used anti-schizophrenic agents were evaluated against T. gondii in human fibroblast cells. Dopamine caused a significant increase in tachyzoite numbers at 250 nM but not 100 nM and the drugs valproic acid, fluphenazine, thioridazine and trifluoperazine inhibited T. gondii development. The effects T. gondii infection had on behavior were examined using a congenital mouse model. Previous work demonstrated maternal immune stimulation (MIS) with interferon gamma (INF-g) resulted in decreased fetal mortality from congenital T. gondii infections; therefore I examined the effects of INF- g treatment of mothers to determine if protection from the behavioral effects of T. gondii occurred in their offspring. No differences in concentrations of neurotransmitters in the brains of congenitally infected mice were observed. I found that mice infected with T. gondii developed adult onset behavior impairments with decreased rate of learning, increased activity and decreased memory, indicating cognitive impairment for male mice and not female mice. My findings support the evidence T. gondii is a factor in the development of cognitive impairments. My results for T. gondii exposed male mice are consistent with the convention that males have more cognitive impairments in the prodromal stage of schizophrenia. MIS with IFN-g had a minimal effect on behavior post sexual maturity but had a greater effect on pre sexual maturity female mice which exhibited difficulties with spatial memory, coordination and the ability to process stimuli. The results indicate the behavior alterations from IFN- g are transient. When MIS is given prior to congenital infection with T. gondii, we detected no behavior deficits in any group of mice, including male mice post sexual maturity. Based on the results of my study, I must reject the hypothesis that neurotransmitter levels are influenced by congenital toxoplasmosis and accept the hypothesis that congenital T. gondii infection caused cognitive impairments in male mice post sexual maturity.
Ph. D.
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7

Anderson, Paul Michael. "Oscillations dans la bande de fréquence gamma dans des modèles de rongeurs pour la schizophrénie". Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ025/document.

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La schizophrénie est un trouble mental débilitant qui se caractérise par des perturbations de la pensée, des émotions et de la cognition. Ces processus d’intégration fonctionnelle sont généralement associés à des oscillations bioélectriques cérébrales synchrones dans la bande de fréquence gamma (30-80 Hz), lesquelles sont aussi altérées chez des patients souffrant de schizophrénie. Ce travail de thèse vise à développer des méthodes et des outils pour étudier les mécanismes neuronaux sous-tendant les altérations de ces oscillations physiopathologiques. Pour ce faire, nous avons développé des modèles de rongeurs de laboratoire pour la schizophrénie. Nous avons démontré que des modifications génétiques ou pharmacologiques conduisent à des perturbations des oscillations gamma et que des médicaments antipsychotiques peuvent les moduler
Schizophrenia is a debilitating mental disorder that is characterised by a breakdown in normal thought processes, blunted emotional responses and a variety of cognitive difficulties. Gamma frequency (30 – 80 Hz) oscillations are associated with many processes that are disrupted in people with schizophrenia memory, perception and attention. This thesis aimed to develop methods and tools to investigate the basic mechanisms that underlie the alterations in gamma frequency brain activity that are observed in patients suffering from schizophrenia. To do this we developed a variety of experimental animal models for schizophrenia. We successfully demonstrated that both genetic and pharmacological changes lead to alterations in gamma oscillations and that antipsychotic medications can modulate them
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8

Cherouali, Toufik. "Caractérisation et implantation de la stimulation mécanique de la boucle neuromusculaire gamma sur une machine isocinétique". Reims, 2004. http://theses.univ-reims.fr/exl-doc/GED00000049.pdf.

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Ce travail porte sur le développement d'une nouvelle méthode d'aide au renforcement musculaire et de son implantation sur une machine d'entraînement et de rééducation. A travers l'étude des boucles de régulation du muscle, nous avons montré qu'il est possible d'exciter volontairement la boucle neuromusculaire gamma en provoquant mécaniquement des étirements du muscle pendant sa contraction. La caractérisation des paramètres nécessaires à sa mise en œuvre pratique a été abordé à travers un modèle de simulation du muscle. Une spécification de tout les entraînements de la machine a été ensuite proposée pour intégrer la stimulation mécanique. Dans ce cadre un schéma de commande reposant sur une boucle de vitesse et sur un contrôleur en force a été proposé afin d'intégrer les profils de force de la stimulation. Une phase de validation expérimentale a permit d'illustrer une séance complète d'entraînement, de sa création à l'analyse des résultats et de valider les lois de commandes implantées
This work describes the characterization, implementation, and evaluation of mechanical stimulation with a view to enhancing muscular force by exploiting the effect of the neuromuscular gamma loop (NGL). After a study of the characteristics of muscle, a functional regulation diagram is proposed. Then, the specification and characterization of stimulation patterns allowed to identify the parameters required for the implementation on an isokinetic machine. After an adaptation of the control system of the machine, we have proposed a generic force based control scheme for Isokinetic machines. This controller carries out small movements used to stretch muscle, and this repeated stretching invokes the NGL during exercise. Some experimental results illustrate the efficiency of the proposed controllers and provide interesting results that can be easily exploited by the domain specialists to develop suitable training protocols using mechanical stimulation
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9

Schmidt, Oliver. "The effects of macrophage-stimulating protein and gamma synuclein on the development of brainstem motor systems". Thesis, University of Edinburgh, 2002. http://hdl.handle.net/1842/30728.

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Here, the effects of macrophage-stimulating protein (MSP) and γ-synuclein on two systems in the developing brainstem involved in controlling movement have been studied: a) the cranial motoneurons and b) the dopaminergic neurons of the substantia nigra and the ventral tegmental area. MSP exerts a variety of biological actions on many cell types, but has no known functions in the brain. To investigate whether MSP is also capable of acting as a neurotrophic factor, hypoglossal motoneurons were purified from the embryonic chicken hindbrain because these neurons are known to express the MSP receptor tyrosine kinase RON. The study shows that MSP promotes the in vitro survival of these neurons during the period of naturally occurring neuronal cell death and enhances the growth of neurites from these neurons. Furthermore, MSP mRNA was detected in the developing tongue which is the target tissue for hypoglossal neurons. These studies demonstrate that MSP is a neurotrophic factor for a distinct population of developing motoneurons. γ-synuclein is a recently discovered member of the synuclein family. Another member of this family, α-synuclein has been implicated in the pathogenesis of Parkinson’s disease. However, little is known about the function of γ-synuclein and it has not yet been directly implicated in the genesis of neurodegenerative conditions. Here, brainstems of transgenic mice lacking γ-synuclein have been analysed by means of immunohistochemical and histological techniques. The data obtained shows that γ-synuclein is expressed in the murine substantia nigra and in most cranial motor nuclei and that the localization of the protein undergoes a shift during development from a cytosomal to an axonal and synaptic localization. Mice lacking γ-synuclein have a deficit of neurons in these structures. In the context of recent studies which have revealed in vivo and in vitro interactions between the synucleins, this data suggests that a fine balance between α- and γ-synuclein seems critical to prevent the demise of certain neurons during the period of naturally occurring cell death. It also indicates that γ-synuclein may play a role in the pathogenesis of Parkinson’s disease.
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10

DeSantis, Dylan David. "CH3NH3PbBr3-xClx Device Characteristics for Gamma Spectroscopy with Simulations of Real Time Pulse Height Analysis". The Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1501878848404021.

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11

Gaci, Mohammed. "Radiothérapie interne (électrons Auger) par stimulation gamma résonante Mössbauer : chimère ou réalité ? : Etudes physico-chimiques, cellulaires et biomoléculaires". Poitiers, 2002. http://www.theses.fr/2002POIT2328.

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Mills et al, 1988 ont proposé l'utilisation pour certaines tumeurs d'une nouvelle forme de thérapie par émission d'électrons Auger induite par stimulation Mössbauer, en utilisant la combinaison d'un vecteur afin de cibler la zone tumorale sensible (bléomycine (BLM)) et d'un émetteur Auger (le 57Fe). Notre travail a consisté à développer cette technique. Nous avons montré que seuls 7 isotopes Mössbauer peuvent être utilisés. L'étude chimique de la complexation du fer à la BLM a été effectuée puis une analyse par spectrométrie Mössbauer des complexes BLM-57Fe et BLM-57Fe ADN et déduit les vitesses spécifiques d'irradiation. Après avoir constaté l'absence d'efficacité (en terme de taux de survie) sur 2 types cellulaires (SW480 et E. Coli), nous avons développé un modèle plasmidique et modulé : le nombre de molécules BLM-57Fe, le facteur f, dose d'irradiation. Nous n'avons pas retrouvé d'efficacité additionnelle définit en terme de cassures double brins (CDB). Nous avons alors vérifié par modélisation Monté Carlo ( modèle BLM-57Fe-plasmide) que les électrons émis par cascade Auger du 57Fe sont efficaces. Nous avons confirmé expérimentalement l'efficacité (en terme d'induction de CDB) en utilisant le modèle plasmide-BLM-55Fe (émetteur radioactif). La stimulation Mössbauer n'est donc pas une technique appropriée en thérapie
Mills and al (1988) proposed to treat superficial tumours a new type of therapy using electrons Auger emission induced by Mössbauer effect. This technique is a combination of a vector to target cellular tumour DNA (here bleomycin (BLM)) and an Auger emitter ( a Mössbauer isotope:57Fe). In this work we define the place of this new therapy, and we show that only seven Mössbauer isotopes can be used. We study chemically the BLM-Fe complex. After, a Mössbauer spectroscopy analysis of the BLM-Fe and BLM-Fe-DNA complex is performed and found velocities to achieve the resonance effect. The survival rates studies on two cellular types (SW480 and E. Coli) found any efficacy. A plasmidic model is developed. We enhance: the number of BLM molecules (1012 and 1013), the non-recoil f-factor, the irradiation dose and we don't found any efficacy defined as double strands breaks (DSB). A Monte Carlo study using BLM-Fe complex with a peace of DNA plasmid is built. This model permitted to show a great efficacy in terms of DSB. Those results are confirmed by a model using BLM-55Fe (radioactive isotope) on PGEM4Z plasmid. It can be conclude that Mössbauer effect is not the appropriate technique in radiotherapy
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Rinke, Andrea. "Synthese von IL-10 und IFN-[gamma] [IFN-gamma] in T-Helferzellen nach Stimulation mit [beta]-Laktoglobulin [Beta-Laktoglobulin] in Abhängigkeit von einer allergischen Sensibilisierung am Ende des ersten Lebensjahres". [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=966209699.

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13

Usami, Kiyohide. "Sleep modulates cortical connectivity and excitability in humans: direct evidence from neural activity induced by single-pulse electrical stimulation". Kyoto University, 2015. http://hdl.handle.net/2433/202800.

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14

Punareewattana, Korawuth. "Immunoteratological Studies of Diabetic Embryopathy Using Gene Expression Analysis". Diss., Virginia Tech, 2003. http://hdl.handle.net/10919/27088.

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Diabetic embryopathy is a major complication of pregnant women with type I diabetes. Immune defects in the pathogenesis of diabetic embryopathy have been suggested. We hypothesized that activated immune system can counteract diabetic effect and result in prevention of diabetic embryopathy. Diabetes was induced in pregnant ICR mice by streptozocin injection. Three different techniques of maternal immune stimulation, complete Freundâ s adjuvant (CFA), granulocyte-macrophage colony-stimulating factor (GM-CSF), or interferon-gamma (IFN-g), were used to stimulate the maternal immune system. Approximately 50% of fetuses from hyperglycemic (>27 mM/L) dams were malformed, with neural tube defects predominating. Maternal immune stimulation during the time of normoglycemia, i.e. prior to onset of hyperglycemia, was necessary for reducing teratogenic effects associated with hyperglycemia. The immune-stimulated diabetic mice then produced significantly lower numbers of malformed fetuses: CFA 20.9%, GM-CSF 23.3%, IFN-g 13.9%. A gene microarray was then used to examine a selected panel of placental and splenic genes. We hypothesized that a shared profile of placental or splenic gene expression changes may correlate to the reduced birth defect outcome induced by the different immune stimulation procedures. Diabetes did not cause significant changes in placenta or spleen gene expression profile. In placenta, CFA and GM-CSF changed placental gene expression relative to control or diabetes, but differentially affected such genes relative to each other; further, IFN-g did not affect gene expression relative to control or diabetes. Thus no common pattern of improved placental cytokine, cell-cycle, apoptotic, transcription factor, or other gene expression was identified in the immune-stimulated mice. In spleen, all 3 immune activators produced a common altered gene expression profile. The overall gene expression profile after all immune stimulation procedures suggested increased splenocyte activity and cytokine production. The cytokine GM-CSF, in particular, was up-regulated in splenic leukocytes. This cytokine has previously been associated with reduced cleft palate in urethane-exposed mice after immune stimulation, and with reduced limb malformations in cyclophosphamide-treated mice after intra-uterine administration. In contrast, the TGF-beta3 gene was down-regulated in immune-stimulated diabetic mice. This gene was up-regulated in urethane-exposed mice, an effect that may be associated with reduced cleft palate. Thus unlike urethane, TGF-beta3 gene expression did not show a relationship with reduced diabetes-induced birth defects. Taken together, these data prove our hypotheses and suggest that mechanistically diverse forms of immune activation result in protection against diabetes-related teratogenesis, but only if given prior to onset of hyperglycemia. Such immune stimulation in mice may act through systemic immune organs, i.e. spleen, over-riding adverse effects of diabetes on development.
Ph. D.
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Zhang, Yi [Verfasser]. "Restored laser evoked potential and decreased gamma band activity in chronic-neuropathic pain patients under dorsal root ganglion stimulation treatment / Yi Zhang". Tübingen : Universitätsbibliothek Tübingen, 2021. http://d-nb.info/1225740185/34.

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Meinel, Thomas Raphael [Verfasser], e Rainer H. [Akademischer Betreuer] Straub. "Neuronale alpha-adrenerge Stimulation von IFN-gamma, IL-6 und CXCL1 in murinen Milzen im Tiermodell der Arthritisspätphase / Thomas Raphael Meinel. Betreuer: Rainer H. Straub". Regensburg : Universitätsbibliothek Regensburg, 2015. http://d-nb.info/1075642272/34.

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17

Hubert, Pascale. "Tyrosine phosphorylation et association à la phospholipase C Gamma-1 de la protéine de 62 KD liée à Gap après stimulation de la molécule CD2 des cellules T Jurkat". Paris 7, 1993. http://www.theses.fr/1993PA07B070.

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Thérier, Julien. "Régulation de la voie des Mitogen-Activated Protein Kinase ERK1/2 par la phospholipase C gamma dans le signal du Macrophage-Colony Stimulating Factor". Lyon 1, 2005. http://www.theses.fr/2005LYO10121.

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Le M-CSF régule l'établissement du lignage monocytaire/macrophagique en assurant la survie, la prolifération mais aussi la différenciation des progéniteurs myéloïdes en cellules très spécialisées : les macrophages. Ce contrôle nécessite la transduction d'un signal intracellulaire impliquant de nombreuses molécules. Parmi celles-ci, les MAPK ERK1/2 présentent une cinétique d'activation caractéristique : une première vague de phosphorylation rapide et transitoire puis une seconde vague tardive et soutenue essentielle à la différenciation macrophagique. J'ai montré au cours de cette étude que la phospholipase C régule spécifiquement cette seconde vague d'activation des kinases ERK1/2 par l'intermédiaire de Ras. Ce processus, indépendant du diacylglycérol, fait intervenir de façon prépondérante l'augmentation du taux de calcium intracellulaire. Ces résultats constituent un mécanisme d'activation original faisant potentiellement intervenir les kinases Src ou les complexes Gab2/SHP2
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Kobayashi, Katsuya. "Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation". Kyoto University, 2015. http://hdl.handle.net/2433/202676.

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20

Khider, Nassim. "Etude de la force et de la vitesse de conduction des potentiels d'action musculaires en relation avec le potassium ou la demande fonctionnelle chez le rat". Compiègne, 2002. http://www.theses.fr/2001COMP1376.

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L'adaptation du muscle strié squelettique ne se manifeste pas uniquement au niveau de sa masse mais aussi au niveau de ses propriétés mécaniques, de ses propriétés métaboliques et de ses propriétés électriques. Notre étude s'inscrit dans le cadre de la problématique générale concernant les relations entre les évènements électriques (vitesse de conduction des potentiels d'action musculaire VCPA) et les évènements métaboliques (lactate et potassium) survenant au niveau d'un muscle soumis à différents régimes d'activité. L'évolution de ces évènements associée à celle des évènements mécaniques a été étudiée lors de la fatigue musculaire induite par stimulation électrique à basse fréquence (2-l0Hz) portée sur le nerf moteur. Nous avons ainsi étudié in vivo et in vitro, le comportement du muscle sa/eus de rat en utilisant deux modèles d'induction de plasticité musculaire, hypoactivité par suspension et hyperactivité par entraînement en endurance. Ceci nous a amené à : étudier l'effet d'un apport exogène de lactate ou de potassium, adapter une technique de scintigraphie et de tomographie synchronisée à notre problématique, afm de suivre la distribution du 201Tl en tant qu'analogue du potassium, envisager l'application pharmacologique que constitue l'évaluation de l'effet antifatigue du malate de citrulline. De l'ensemble des résultats obtenus, il ressort que : le potassium semble stabiliser la concentration du lactate dans le sang et accélérer l'installation du phénomène de fatigue musculaire en tenue de modification de l'activité électrique ; la force générée semble plus sensible aux variations de la concentration de potassium que ne l'est la VCPA ; la variation de demande fonctionnelle du muscle, induit un phénomène de transition en type de fibres qui peut être estimé par la VCPA ; la scintigraphie montre que la captation du thallium par le tissu musculaire dépend de la fréquence de stimulation. Cette étude confinne le lien entre la VCPA, la myotypologie et les propriétés métaboliques du muscle. De plus elle montre l'importance de la VCPA comme indicateur de la composition du muscle en types de fibres et de son état de fatigue.
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21

Sandvold, Haakon [Verfasser]. "Die Rolle von Major-Histocompatibility-Complex Klasse II bei der Proliferation von gamma delta-T-Zellen nach (E)-4-Hydroxy-3-Methyl-But-2-Enyl-Pyrophosphat-Stimulation / Haakon Sandvold". Gießen : Universitätsbibliothek, 2019. http://d-nb.info/1199811777/34.

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22

Cherouali, Toufik Zaytoon Janan. "Caractérisation et implantation de la stimulation mécanique de la boucle neuromusculaire gamma sur une machine isocinétique thèse pour le doctorat en sciences spécialité Génie informatique, Automatique et Traitement du Signal /". Reims : S.C.D. de l'Université, 2005. http://scdurca.univ-reims.fr/exl-doc/GED00000049.pdf.

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23

Dutescu, Ralf Michael [Verfasser], e H. G. [Akademischer Betreuer] Wahl. "Expressionsanalyse der nukleären Rezeptoren PPAR-α/γ-1/γ-2 [PPAR-alpha, gamma-1, gamma-2] und der Transkriptionsfaktoren T-bet und GATA-3 nach Stimulation von dermalen Endothelzellen mit den Weichmacher, Di(2-ethylhexyl)phthalat-Metaboliten-2-Ethylhexanol und 4-Heptanon / Ralf Michael Dutescu. Betreuer: H. G. Wahl". Marburg : Philipps-Universität Marburg, 2011. http://d-nb.info/1013288459/34.

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24

Sun, Yinming. "Deep Brain Stimulation Suppresses Gamma Oscillations in Treatment Resistant Depression". Thesis, 2012. http://hdl.handle.net/1807/35548.

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Background: Major depressive disorder is a debilitating psychiatric condition with high rates of treatment resistance that may be associated with working memory (WM) deficits. For treatment resistant depression (TRD) patients, deep brain stimulation (DBS) is emerging as an effective therapeutic option. Objective: To determine if electroencephalography signals recorded during DBS ON and OFF states while performing WM tasks can serve as biomarkers of therapeutic efficacy for DBS in TRD patients. Results: DBS stimulation suppressed frontal gamma oscillations (30–50Hz) during the ON state relative to the OFF state, an effect that was more pronounced with higher WM load. This suppression strongly correlated with depressive symptoms reduction. Conclusion: Suppression of gamma oscillations by DBS is likely mediated by indirect activation of inhibitory circuits in the frontal cortex. It represents a potential treatment biomarker for DBS in TRD and may lead to more tailored treatment parameters that can result in enhanced efficacy.
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25

Piechulek, Thomas. "Isoenzym-spezifische Stimulation der Phospholipase C-g2 [C-Gamma 2] durch Rac-GTPasen /". 2005. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=014794211&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.

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26

Barr, Mera. "Modulation of Gamma Oscillatory Activity Through Repetitive Transcranial Magnetic Stimulation in Healthy Subjects and Patients with Schizophrenia". Thesis, 2011. http://hdl.handle.net/1807/29662.

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Background: Gamma oscillations (30-80 Hz) in the dorsolateral prefrontal cortex (DLPFC) are associated with working memory; a process involving the maintenance and manipulation of information on line (Baddeley, 1986). Gamma oscillations are supported by gamma-aminobutyric acid (GABA) inhibitory interneurons in the DLPFC. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method in which to stimulate the cortex that has been shown to modify oscillations, cognition and GABAergic mechanisms. Patients with schizophrenia have severe deficits in working memory that may be related to impairments in GABAergic inhibitory neurotransmission underlying gamma oscillations in the DLPFC. Objective: First, to evaluate gamma oscillatory activity in patients with schizophrenia during working memory compared to healthy subjects. Second, to examine the effect of rTMS applied over the DLPFC on gamma oscillations generated during working memory in healthy subjects. Third, to examine the effect of rTMS applied to the DLPFC on gamma oscillations in patients with schizophrenia compared to healthy subjects. Hypotheses: First, it was hypothesized that patients with schizophrenia would exhibit an alteration in gamma oscillatory activity. Second, it was hypothesized that rTMS would be effective in enhancing gamma oscillations in healthy subjects. Third, it was hypothesized that rTMS would be effective in inhibiting gamma oscillations in patients with schizophrenia. Results: The first study found that patients with schizophrenia generate excessive gamma oscillations during working memory compared to healthy subjects. The second experiment found that rTMS over the DLPFC resulted in the potentiation of gamma oscillations in healthy subjects during working memory. The third experiment demonstrated that rTMS inhibited excessive gamma oscillations in patients with schizophrenia while an opposite effect was found in healthy subjects. Conclusions: rTMS applied over the DLPFC modulates frontal gamma oscillatory in healthy subjects and in patients with schizophrenia depending on baseline levels of activity, a finding that may ultimately translate into a better understanding of the mechanisms leading to cognitive improvement in this disorder.
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27

Kretzschmar, Eva. "Stimulation von humanen gamma delta T-Lymphozyten durch Poly-Inosin-: Poly-Cytidyl-Säure (Poly (I:C))". Doctoral thesis, 2006. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-22754.

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Humane gamma delta T-Zellen stellen eine Gruppe von T-Lymphozyten dar, die neben NKT- und NK-Zellen auch als lymphatische Effektorzellen der angeborenen Immunität beschrieben werden. Nach ihrer Stimulierung tragen sie, in Analogie zu den NK-Zellen, zur schnellen, unspezifischen Infektionsabwehr bei. In dieser Arbeit wurde erstmals der Einfluss von ds-RNS (Poly (I:C)) auf humane gamma delta T-Zellen untersucht. Diese Substanz simuliert in vivo und in vitro die Infektion mit einem Virus und übt pleiotrope Effekte auf eine Reihe von verschiedenen Zellen aus, u. a. auch auf NK-Zellen. Diese Arbeit beschreibt die potente kostimulierende Wirkung von Poly (I:C) auch auf gamma delta T-Zellen: Es induziert deren partielle Aktivierung, sichtbar am Oberflächenmolekül CD69. Daneben stimuliert die ds-RNS die Antigen-spezifische gamma delta T-Zell-Antwort, nachweisbar an einer Zunahme der Proliferation. Die Sekretion von IFN-gamma durch gamma delta T-Zellen ist jedoch nicht gesteigert. Die Wirkungsmechanismen von Poly (I:C) auf gamma delta T-Zellen sind, im Gegensatz zu den NK-Zellen, in erster Linie indirekt. Durch Depletion von CD11c-positiven dendritischen Zellen wird die Poly (I:C)-vermittelte Aktivierung der gamma delta T-Zellen vollständig aufgehoben. Ebenso kann durch Neutralisierung von Typ I Interferonen, die v. a. nach Poly (I:C)-vermittelter Stimulation dieser DCs sezerniert werden, größtenteils eine Aufhebung der Poly (I:C)-vermittelten CD69-Expression auf gamma delta T-Zellen erzielt werden. Diese Ergebnisse legen eine Antigen-unabhängige, schnelle Aktivierung von gamma delta T-Zellen im Rahmen viraler Infektionen nahe
Human gamma delta T cells are a subset of T lymphocytes, belonging to lymphatic effector cells of innate immunity beside NKT cells and NK cells. After stimulation they contribute in analogy of NK cells to rapid unspecific immune responses. This work investigated for the first time the effect of a double-stranded RNA (mimicked by poly (I:C)) to human gamma delta T cells. This substance simulates a virus infection in vivo and in vitro and exerts pleiotrophic effects on NK cells among a variety of different cells. The thesis states that poly (I:C) has potent gamma delta T cell co-stimulatory capacity: Within PBMCs gamma delta T cells are partially activated expressing increased levels of CD69. Beside this poly (I:C) co-stimulates an antigen-mediated proliferation in response to IPP. The secretion of IFN-gamma isn’t enhanced however. The effect of poly (I:C) on gamma delta T cells is mediated mainly indirectly, in contrast to NK cells. Depletion of CD11+ dendritic cells abrogates the poly (I:C)-mediated activation of gamma delta T cells completely. Neutralizing antibodies against interferons type I secreted by activated DCs almost completely prevent the poly (I:C)-mediated up-regulation of CD69 on gamma delta T cells. These results indicate an antigen independent rapid activation of gamma delta T cells during viral infections
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28

"Gamma Band Oscillation Response to Somatosensory Feedback Stimulation Schemes Constructed on Basis of Biphasic Neural Touch Representation". Doctoral diss., 2017. http://hdl.handle.net/2286/R.I.45529.

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abstract: Prosthetic users abandon devices due to difficulties performing tasks without proper graded or interpretable feedback. The inability to adequately detect and correct error of the device leads to failure and frustration. In advanced prostheses, peripheral nerve stimulation can be used to deliver sensations, but standard schemes used in sensorized prosthetic systems induce percepts inconsistent with natural sensations, providing limited benefit. Recent uses of time varying stimulation strategies appear to produce more practical sensations, but without a clear path to pursue improvements. This dissertation examines the use of physiologically based stimulation strategies to elicit sensations that are more readily interpretable. A psychophysical experiment designed to investigate sensitivities to the discrimination of perturbation direction within precision grip suggests that perception is biomechanically referenced: increased sensitivities along the ulnar-radial axis align with potential anisotropic deformation of the finger pad, indicating somatosensation uses internal information rather than environmental. Contact-site and direction dependent deformation of the finger pad activates complimentary fast adapting and slow adapting mechanoreceptors, exhibiting parallel activity of the two associate temporal patterns: static and dynamic. The spectrum of temporal activity seen in somatosensory cortex can be explained by a combined representation of these distinct response dynamics, a phenomenon referred in this dissertation to “biphasic representation.” In a reach-to-precision-grasp task, neurons in somatosensory cortex were found to possess biphasic firing patterns in their responses to texture, orientation, and movement. Sensitivities seem to align with variable deformation and mechanoreceptor activity: movement and smooth texture responses align with potential fast adapting activation, non-movement and coarse texture responses align with potential increased slow adapting activation, and responses to orientation are conceptually consistent with coding of tangential load. Using evidence of biphasic representations’ association with perceptual priorities, gamma band phase locking is used to compare responses to peripheral nerve stimulation patterns and mechanical stimulation. Vibrotactile and punctate mechanical stimuli are used to represent the practical and impractical percepts commonly observed in peripheral nerve stimulation feedback. Standard patterns of constant parameters closely mimic impractical vibrotactile stimulation while biphasic patterns better mimic punctate stimulation and provide a platform to investigate intragrip dynamics representing contextual activation.
Dissertation/Thesis
Doctoral Dissertation Biomedical Engineering 2017
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29

Eckstein, Susanne. "Stimulation humaner V-Gamma-9-V-Delta-2-T-Lymphozyten : Untersuchungen zur Wirkung Stickstoff-haltiger Bisphosphonate und zu bakteriellen Phosphoantigenen". Doctoral thesis, 2004. https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-12140.

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In der vorliegenden Arbeit werden Studien zu verschiedenen Aspekten der Stimulation von humanen Vg9Vd2-T-Lymphozyten vorgestellt. Ein Schwerpunkt war die Charakterisierung der Erkennung von Bisphosphonaten durch Vg9Vd2-T-Zellen. Weder die Alkylmonophosphonate Ethyl- und Propylphosphonat noch 3-Aminopropylphosphonat bewirkten eine Stimulation von Vg9Vd2 T-Lymphozyten. Anscheinend ist also für die gd-T-Zell-stimulierende Aktivität von Aminobisphosphonaten das Vorhandensein sowohl der Methylenbisphosphonat-Gruppe als auch des Amino-Stickstoffs entscheidend. Es wurden verschiedene Pamidronat-Derivate untersucht, die sich durch Substituenten am Stickstoffatom unterscheiden. Die meisten dieser Verbindungen konnten Vg9Vd2-T-Zellen aktivieren, die Art der Substituenten hatte aber großen Einfluss darauf, welche Konzentration des jeweiligen Bisphosphonats für eine gd-T-Zell-Antwort nötig war. Besonders negativ auf die gd-T-Zell-stimulierende Aktivität wirkte sich aus, wenn das Stickstoffatom Teil einer Säureamidbindung war. Das lässt darauf schließen, dass die Gegenwart einer positiven Ladung (durch Protonierung des Stickstoffatoms) von Bedeutung für die Bioaktivität dieser Verbindungen ist. Beim Vergleich verschiedener Bisphosphonate mit stickstoffenthaltenden Heteroaromaten (Fünfringe mit ein bis drei Stickstoffatomen) zeigte sich, dass sowohl die Position des basischen Stickstoffatoms im Ring als auch Art und Position von Ringsubstituenten Einfluss auf deren gd-T-Zell-stimulierende Aktivität haben. Es ergaben sich Hinweise, dass sich eine gesteigerte Neigung eine positive Ladung in der Seitenkette zu tragen bei diesen Verbindungen genau wie bei Aminobisphosphonaten günstig auf das gd-T-Zell-aktivierende Potential auswirkt. Durch Behandlung mit Zoledronat wurde die monozytäre Zelllinie THP-1 stimulierend für Vg9Vd2-T-Zellen. Auch weitere Zelllinien und Lymphozyten des peripheren Bluts (PBL) konnten nach Vorinkubation mit Zoledronat Vg9Vd2-T-Zellen aktivieren. Dabei genügten bei den PBL deutlich geringere Zoledronat-Konzentrationen um einen Effekt zu erzielen als bei den untersuchten Zelllinien. Für die indirekte Stimulation von Vg9Vd2-T-Zellen durch Zoledronat mittels THP-1 Zellen oder PBL war Zell-Zell-Kontakt zwischen den präsentierenden Zellen und den gd-T-Zellen Voraussetzung. Die Anwesenheit von alkalischer Phosphatase hatte keine Auswirkungen auf die gd-T-Zell-Aktivierung durch Zoledronat. Dies spricht dafür, dass Vg9Vd2-T-Zellen Oberflächenstrukturen auf anderen Zellen erkennen und dass freie Phosphoantigene bei der gd-T-Zell-Stimulierung durch Stickstoff enthaltende Bisphosphonate keine Rolle spielen. Wurde die Vorinkubation von THP-1 Zellen mit Zoledronat in Gegenwart von Saponin, einem Detergenz das die Durchlässigkeit der Zellmembran reversibel erhöht, durchgeführt, reichten deutlich niedrigere Konzentrationen des Bisphosphonats aus, um die THP-1 Zellen stimulierend für gd-T-Lymphozyten zu machen. Das ist ein Hinweis darauf, dass für die Aktivierung von Vg9Vd2-T-Zellen durch Zoledronat intrazelluläre Vorgänge in den „antigenpräsentierenden“ Zellen verantwortlich sein könnten. Beim Vergleich verschiedener N-BPs hinsichtlich ihrer Aktivität gegenüber gd-T-Zellen und ihrer antiresorptiven Potenz ergab sich eine erstaunlich gute Korrelation. Dies könnte darauf hinweisen, dass beide Effekte durch den gleichen Mechanismus – die Hemmung der Farnesylpyrophosphat-Synthase – zustande kommen. Die Gegenwart von Farnesol oder Geranylgeraniol während der Vorinkubation von THP-1 Zellen mit Zoledronat verringerte deren gd-T-Zell-stimulierendes Potential nicht, so dass vielleicht nicht die Verarmung an längerkettigen Isoprenoiden sondern die Anreicherung von Vorläufern zu Veränderungen in den Zellen führt, die diese schließlich erkennbar für Vg9Vd2-T-Zellen machen. Zusätzlich wurden im Rahmen dieser Arbeit einige Versuche zu bakteriellen Phosphoantigenen durchgeführt. Mittels einer selektiven HPLC-MS/MS-Methode gelang uns in einer E. coli-Probe der Nachweis eines Vg9Vd2-T-Zell-stimulierenden Pyrophosphats mit der molekularen Masse von 3-Formyl-1-butyl-pyrophosphat, einem Phosphoantigen das in Mykobakterien gefunden worden war (Belmant und Mitarbeiter, 1999). Eine weitere Strukturaufklärung war aufgrund der äußerst geringen Konzentration des Phosphoantigens nicht möglich. 2-C-Methyl-D-erythritol-2,4-cyclodiphosphat (MEcPP) ist ein Zwischenprodukt des 2-C-Methylerythritol-4-phosphat- (MEP) Wegs der Isoprenoidbiosynthese. Es wird in manchen Bakterien – z. B. Corynebacterium ammoniagenes – bei oxidativem Stress verursacht durch Benzylviologen (BV) akkumuliert. Es konnte gezeigt werden, dass Extrakte aus C. ammoniagenes, die in Gegenwart von BV kultiviert wurden, in einem höherem Maße Vg9Vd2-T-Zellen stimulieren als Proben von Bakterien, die ohne BV-Zusatz wuchsen; MEcPP wirkte selbst nicht als Phosphoantigen. Dies war ein weiterer Hinweis darauf, dass bakterielle Phosphoantigene mit dem MEP-Weg assoziiert sind
The present work focuses on different aspects of human Vg9Vd2 T lymphocyte stimulation. A main focus of this work was the characterisation of bisphosphonate recognition by Vg9Vd2 T cells. Neither the alkyl monophosphonates ethyl and propyl phosphonate nor 3-aminopropylphosphonate were able to stimulate Vg9Vd2 T lymphocytes. Apparently both the methylene bisphosphonate group and the amino group are crucial for the Vg9Vd2 T cell stimulating ability of aminobisphosphonates. We examined pamidronate derivates bearing different substituents at the nitrogen atom. Most of these compounds activated Vg9Vd2 T cells. But the nature of the substituent greatly influenced the bisphosphonate concentration necessary for gd T cell stimulation. When the nitrogen was part of an amide bond, there was a pronounced negative effect on the Vg9Vd2 T cell stimulating capacity. It can be concluded that the bioactivity of bisphosphonates depends on the presence of a positive charge (through protonation of the nitrogen atom). Comparing different bisphosphonates with nitrogen containing heteroaromatic side chains (five membered rings containing one to three nitrogen atoms) we found that the position of the basic nitrogen in the ring as well as the nature and position of ring substituents influenced their gd T cell stimulating activity. There was evidence that a higher tendency towards a positive charge in the side chain had a positive effect on the Vg9Vd2 T cell activating potential of these compounds, as we also found for aminobisphosphonates. Zoledronat pulsed cells of the monocytic cell line THP-1 stimulated Vg9Vd2 T cells. Other cell lines and peripheral blood lymphocytes (PBL) also activated Vg9Vd2 T cells after incubation with zoledronate. There was a distinctly lower concentration of zoledronate needed for PBL to become stimulatory as for the analyzed cell lines. Cell-cell-contact between the presenting cells and the Vg9Vd2 T cells was necessary for the indirect stimulation by zoledronate pulsed THP-1 cells or PBL. Alkaline phosphatase did not abolish the gd T cell activation by zoledronate. That points to the possibility that Vg9Vd2 T cells recognize surface structures on other cells and that free phosphoantigens are not involved in gd T cell stimulation by nitrogen containing bisphosphonates. When THP-1 cells were incubated with zoledronic acid in the presence of saponin, a detergent that reversibly enhances the permeability of the cell membrane, the bisphosphonate concentration needed for rendering THP-1 cells gd T cell stimulating was clearly reduced. That indicated that intracellular events caused by zoledronate (and other nitrogen containing bisphosphonates) in the “antigen presenting cells” could result in their stimulating activity. Comparing the gd T cell stimulating activity of various N-BPs with their antiresorptive potency produced an amazingly good correlation. This could indicate that both effects are based on the same mechanism – the inhibition of farnesyl pyrophosphate synthase. The presence of farnesol or geranylgeraniol during the incubation of THP-1 cells with zoledronate did not diminish their gd T cell stimulating potential. So maybe not the depletion of longer chain isoprenoids but the accumulation of precursors results in changes that finally render the cells recognisable by Vg9Vd2 T lymphocytes. Within the scope of this work we also conducted experiments concerning bacterial phosphoantigens. Using a selective HPLC-MS/MS method we detected in Escherichia coli a Vg9Vd2 T cell stimulating pyrophosphate with the molecular mass of 3-Formyl-1-butyl pyrophosphate, a phopsphoantigen found in mycobacteria (Belmant et al., 1999). Due to the exceedingly low concentration of the phosphoantigen no further structure determination was possible. 2-C-Methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP) is an intermediate of the 2-C-Methylerythritol 4-phosphate (MEP) pathway of isoprenoid biosyntheses. In some bacteria like Corynebacterium ammoniagenes this compound is accumulated under conditions of oxidative stress caused by benzyl viologen (BV). We showed that C. ammoniagenes extracts from bacteria cultivated in the presence of BV had a higher Vg9Vd2 T cell stimulating capacity than from bacteria growing without addition of BV. MEcPP itself was not a phosphoantigen. That was further evidence for the association of bacterial phosphoantigens with the MEP-pathway
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MORELLO, Enrico. "IFN-γ induced by PHA stimulation as new marker for GvHD prediction in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT)". Doctoral thesis, 2011. http://hdl.handle.net/11562/350426.

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Abstract (sommario):
Introduzione La GVHD è la principale complicanza del trapianto allogenico di CSE ed è associata ad considerevole morbidità e mortalità. Una diagnosi precoce può migliorare l'outcome del trapianto. L'effetto delle citochine Th1 come l'IFN-γ è cruciale nella patogenesi del GVHD. Scopo della tesi e metodi La nostra ipotesi è che il monitoraggio dell'INF-Y dopo stimolo con PHA può aiutare il clinico nella gestione della GVHD. Un recente test ELISA (QuantiFERON®-CMV) è in grado di misurare la produzione di IFN-γ in whole blood in seguito a stimolo aspecfico. Lo scopo dello studio è quello di validare il metodo come biomarker di GVHD. Methods: QuantiFERON®‑CMV è un test diagnostico in vitro che usa un cocktail di antigeni di cytomegalovirus (CMV) per stimolare le cellule di sangue intero a produrre INF-Y. I campioni di plasma vengono stimolati da mitogeno (PHA) come controllo positivo. Dosaggio di IFN-γ con ELISA identifica le risposte. Per associare la GVHD con la produzione di INF-Y indotta da PHA abbiamo considerato 3 valori differenti di cutoff: 1) 0,5 IU/mL definito dal produttore, 2) 9 IU/mL definito sperimentalmente come la mediana dei campionamenti dei dati preliminari, 3) 5 IU/mL definito dalla mediana dei campionamenti dello studio prospettico. La diagnosi di GVHD era classificata in accordo con i criteri NCI. Trentasei pazienti sono stati arruolati e monitorati prospetticamente dopo trapianto ai seguenti timepoints: ogni 2-3 settimane fino a +180gg, successivamente mensilmente. Gli eventi(GVHD acuta e cronica, recidiva, morte) venivano registrati e i dati associati alla produzione di INF-Y indotta da PHA; in caso di GVHD era raccomandata la biopsia. Un modello di Cox a 2 step è stato utilizzato per l'analisi statistica per definire i fattori di rischio per lo sviluppo di GVHD. Results INF-Y indotto da PHA aumenta successivamente nei primi 3 mesi dal trapianto ed è associato indipendentemente allo sviluppo di GVHDall'analisi multivariata the multivariate analysis (p= 0.021 al primo mese, 0.015 al secondo, 0.027 al terzo) assieme al sesso (femmina), età, fonte di staminali, profilassi della GvHD e infezioni. La sensibilità del test era del 97% al cutoff 1 (0.5 IU/mL). La riduzione dell'INF-Y indotto da PHA è stata rilevata in tutti i pazienti trattati con immunosoppressione per GVHD eccetto in uno che ha sviluppato in una GVHD cronica steroide resistente. Conclusioni L'INF-Y indotto da PHA è un marker affidabile di GVHD e può aiutare il clinico nella gestione del trattamento. Ulteriori studi sono necessari per definire meglio i setting di pazienti che possono beneficiare di questo test in modo ottimale.
Introduction GVHD is associated with a high morbidity and mortality in alloSCT patients. An early diagnosis of GVHD could reduce this adverse impact on the outcome of alloSCT. The effect of Th1 cytokine IFN-γ is crucial in the pathogenesis of GVHD and, as expected, higher protein levels are reported in the serum of patients with active chronic GVHD. Aims and Methods Our hypotesis is that the monitoring of IFN-γ basal levels as well as IFN-γ induced by mitogen stimulation in the blood samples of patients after alloSCT could help the management and the prediction of GVHD. A recent ELISA based test (QuantiFERON®-CMV) could measure specific (anti-CMV) and aspecific production of IFN-γ in whole blood. The aim of this study is to assess the reliability of the positive control of the QuantiFERON®-CMV kit as new marker for GVHD early diagnosis during immune system reconstitution after bone marrow transplantation. Methods: QuantiFERON®‑CMV is an in vitro diagnostic test that use an antigenic human cytomegalovirus proteins (CMV) peptide cocktail to stimulate cells from whole blood and is used after alloSCT to monitor the occurrence of CMV infection. The mitogen-stimulated (PHA) plasma sample is used as a positive control for each specimen tested. Detection of interferon-γ (IFN-γ) by ELISA is used to identify responses. In order to assess the association between PHA stimulation IFN-γ production and GVHD, we decided to consider 3 different positivity of the test: 1) 0,5 IU/mL as defined by manufacturer, 2) 9 IU/mL as experimentally defined by the median of the observations in our preliminary data set. 3) 5 IU/mL as defined by the median of the values of the prospective study. GVHD extension was defined by Seattle criteria and/or the number of involved sites. A prospective study has been designed in order to confirm these data. Thirty-six patients were prospectively monitored after transplant with QuantiFERON®‑CMV according the following timepoints: every 2-3 weeks until +180d since transplantation, every month until +365d. Lymphocyte subpopulations +28, +56, +84, every month thereafter. Events (acute GVHD, chronic GVHD, relapse, death are registered in the database and matched with the production of PHA induced INF-y; when GVHD was suspected a biopsy of the target organ was recommended. A two step cox regression model for time dependent variables was implemented in order to define risk factors for cGvHD. Results PHA-induced INF-Y increase in the first three months after alloHSCT was independently associated with cGvHD at the multivariate analysis (p= 0.021, 0.015, 0.027 respectively) together with recipient sex (female), age, stem cell source, GvHD prophylaxis and infections. The sensitivity of the test was 97% at the cutoff 1 (0.5 IU/mL). The reduction of PHA-induced INF-Y was detected in all patients treated for a cGvHD but one who did not respond to immune-suppression. Conclusions PHA-induced INF-Y is a reliable biomarker of cGvHD and could help the physician in the management of cGvHD treatment. Further studies are needed in order to better define subsets of patients who could benefit from this test.
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Kretzschmar, Eva [Verfasser]. "Stimulation von humanen γδ-T-Lymphozyten [Gamma-delta-T-Lymphozyten] durch Poly-Inosin-:Poly-Cytidyl-Säure (Poly (I:C)) / vorgelegt von Eva Kretzschmar". 2007. http://d-nb.info/984358943/34.

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32

Sundaram, Arun N. E. "Saccade Related Gamma Potentials Recorded in Human Subthalamic Nucleus, Globus Pallidus Interna and Ventrointermediate Nucleus of the Thalamus". Thesis, 2012. http://hdl.handle.net/1807/33702.

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Abstract (sommario):
Gamma oscillations of local field potentials (LFP) in the basal ganglia and thalamus had not been studied during saccades. Eleven patients were studied during deep brain stimulation (DBS); 6 were in the subthalamic nucleus (STN); 3 in the globus pallidus interna (GPi); and 2 in the thalamic ventralis intermedius nucleus (Vim). Patients performed horizontal saccades to visual targets while LFPs from DBS electrodes, scalp electroencephalogram (EEG), and electrooculogram (EOG) were recorded. Wavelet spectrograms were generated and saccade onset and event-related gamma synchronizations (ERS) were compared to baseline without eye motion. ERS were recorded at and after saccade onset in the STN, GPi and Vim, EEGs and EOGs; but were absent during target light illumination without saccades. ERS were symmetric in all DBS contacts and appeared identical in DBS LFPs, frontal EEGs and EOGs. These findings indicate their origin from extraocular muscle spike potentials rather than brain neural activity.
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33

Heinz, Torsten Joseph. "Immunreaktionen im zentralen Nervensystem bei Stimulation mit Bestandteilen von Borrelia burgdorferi". Doctoral thesis, 2014. http://hdl.handle.net/11858/00-1735-0000-0022-60A8-B.

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34

Weigt, Henning [Verfasser]. "Induktion einer TH1-Reaktion nach Stimulation von dendritischen Zellen mit MALP-2 und IFN-γ [IFN-gamma] in einem In-vitro-Allergiemodell / von Henning Weigt". 2003. http://d-nb.info/96929235X/34.

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35

Shymanets, Aliaksei [Verfasser]. "Struktur-Funktionsanalyse der Gßγ-vermittelten [Gbetagamma-vermittelten] Aktivierung der Phosphoinositid-3-Kinase -γ [Phosphoinositid-3-Kinase-gamma] = Structural and functional analysis of Gßγ-induced [Gbetagamma-induced] stimulation of phosphoinositide 3-kinase γ [phosphoinositide 3-kinase gamma] / vorgelegt von Aliaksei Shymanets". 2007. http://d-nb.info/984855610/34.

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36

Eckstein, Susanne [Verfasser]. "Stimulation humaner Vγ9Vδ2-T-Lymphozyten [V-Gamma-9-V-Delta-2-T-Lymphozyten] : Untersuchungen zur Wirkung Stickstoff-haltiger Bisphosphonate und zu bakteriellen Phosphoantigenen / vorgelegt von Susanne Eckstein". 2005. http://d-nb.info/976079607/34.

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[Verfasser], Dinh Hoang Danh Khoa. "Proteomic analysis of the response of murine bone marrow derived macrophages to IFN-γ [IFN gamma] stimulation and infection with Staphylococcus aureus / vorgelegt von Dinh Hoang Dang Khoa". 2010. http://d-nb.info/1011700514/34.

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38

Stolk, Christine [Verfasser]. "Bestimmung von Interferon γ [gamma] nach In-vitro- und In-vivo-Stimulation von peripheren Blutlymphozyten im Woodchuck mit rekombinantem humanem Interleukin 12 / vorgelegt von Christine Stolk, geb. Pohl". 2008. http://d-nb.info/992318335/34.

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39

Rinke, Andrea [Verfasser]. "Synthese von IL-10 und IFN-γ [IFN-gamma] in T-Helferzellen nach Stimulation mit β-Laktoglobulin [Beta-Laktoglobulin] in Abhängigkeit von einer allergischen Sensibilisierung am Ende des ersten Lebensjahres / vorgelegt von Andrea Rinke". 2001. http://d-nb.info/966209699/34.

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40

Toloe, Johan. "Effects of α/β/γ-Synuclein overexpression on the mitochondria and viability of neurons, examined using genetically encoded fluorescent sensors". Doctoral thesis, 2014. http://hdl.handle.net/11858/00-1735-0000-0023-98DB-7.

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