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Earliest Changes (earliest + change)
Selected AbstractsElectrophysiological Changes In Diabetic Neuropathy: From Subclinical Alterations To Disabling AbnormalitiesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000M. Baba Clinical spectrum of diabetic neuropathy is variable; it may be asymptomatic, but once established, it becomes irreversible and disabling. Some investigators suggested that earliest change in diabetic nerve function is alteration in axonal excitability due to alterations in ion conductance of axon membrane, although these functional changes of ion channels necessarily cause permanent damage or degeneration of nerve fibers. Among various parameter of nerve conduction study in diabetics, prolonged F-wave latency in the peroneal and tibial nerve seems the commonest abnormality in asymptomatic patients. Decrease in amplitude of compound sensory action potential of sural nerve is another earlier abnormality, which is, then, accompanied by a fall in motor amplitude of peroneal and tibial nerves in advanced patients. In disabled patients no motor response is often elicited in the legs. Previous electrophysiological studies could not make clear if central axons were involved or not in diabetic neuropathy. Recently, our group has demonstrated that somatosensory central conduction from the spinal cord to the sensory cortex is delayed in diabetics as well as in the peripheral conduction, which might be partly responsible for the irreversible clinical presentation of diabetic neuropathy. [source] Anticipating bipedalism: trabecular organization in the newborn iliumJOURNAL OF ANATOMY, Issue 6 2009Craig A. Cunningham Abstract Trabecular bone structural organization is considered to be predominantly influenced by localized temporal forces which act to maintain and remodel the trabecular architecture into a biomechanically optimal configuration. In the adult pelvis, the most significant remodelling forces are believed to be those generated during bipedal locomotion. However, during the fetal and neonatal period the pelvic complex is non-weight bearing and, as such, structural organization of iliac trabecular bone cannot reflect direct stance-related forces. In this study, micro-computed tomography scans from 28 neonatal ilia were analysed, using a whole bone approach, to investigate the trabecular characteristics present within specific volumes of interest relevant to density gradients highlighted in a previous radiographic study. Analysis of the structural indices bone volume fraction, trabecular thickness, trabecular spacing and trabecular number was carried out to quantitatively investigate structural composition. Quantification of the neonatal trabecular structure reinforced radiographic observations by highlighting regions of significant architectural form which grossly parallel architectural differences in the adult pattern but which have previously been attributed to stance-related forces. It is suggested that the seemingly organized rudimentary scaffold observed in the neonatal ilium may be attributable to other non-weight bearing anatomical interactions or even to a predetermined genetic blueprint. It must also be postulated that whilst the observed patterning may be indicative of a predetermined inherent template, early non-weight bearing and late stance-related locomotive influences may subsequently be superimposed upon this scaffolding and perhaps reinforced and likely remodelled at a later age. Ultimately, the analysis of this fundamental primary pattern has core implications for understanding the earliest changes in pelvic trabecular architecture and provides a baseline insight into future ontogenetic development and bipedal capabilities. [source] Preferential Resistance of Dopaminergic Neurons to the Toxicity of Glutathione Depletion Is Independent of Cellular Glutathione Peroxidase and Is Mediated by TetrahydrobiopterinJOURNAL OF NEUROCHEMISTRY, Issue 6 2000Ken Nakamura Abstract: Depletion of glutathione in the substantia nigra is one of the earliest changes observed in Parkinson's disease (PD) and could initiate dopaminergic neuronal degeneration. Nevertheless, experimental glutathione depletion does not result in preferential toxicity to dopaminergic neurons either in vivo or in vitro. Moreover, dopaminergic neurons in culture are preferentially resistant to the toxicity of glutathione depletion, possibly owing to differences in cellular glutathione peroxidase (GPx1) function. However, mesencephalic cultures from GPx1-knockout and wild-type mice were equally susceptible to the toxicity of glutathione depletion, indicating that glutathione also has GPx1-independent functions in neuronal survival. In addition, dopaminergic neurons were more resistant to the toxicity of both glutathione depletion and treatment with peroxides than nondopaminergic neurons regardless of their GPx1 status. To explain this enhanced antioxidant capacity, we hypothesized that tetrahydrobiopterin (BH4) may function as an antioxidant in dopaminergic neurons. In agreement, inhibition of BH4 synthesis increased the susceptibility of dopaminergic neurons to the toxicity of glutathione depletion, whereas increasing BH4 levels completely protected nondopaminergic neurons against it. Our results suggest that BH4 functions as a complementary antioxidant to the glutathione/glutathione peroxidase system and that changes in BH4 levels may contribute to the pathogenesis of PD. [source] Microarray analysis of chitin elicitation in Arabidopsis thalianaMOLECULAR PLANT PATHOLOGY, Issue 5 2002Katrina M. Ramonell Summary Chitin oligomers, released from fungal cell walls by endochitinase, induce defence and related cellular responses in many plants. However, little is known about chitin responses in the model plant Arabidopsis. We describe here a large-scale characterization of gene expression patterns in Arabidopsis in response to chitin treatment using an Arabidopsis microarray consisting of 2375 EST clones representing putative defence-related and regulatory genes. Transcript levels for 71 ESTs, representing 61 genes, were altered three-fold or more in chitin-treated seedlings relative to control seedlings. A number of transcripts exhibited altered accumulation as early as 10 min after exposure to chitin, representing some of the earliest changes in gene expression observed in chitin-treated plants. Included among the 61 genes were those that have been reported to be elicited by various pathogen-related stimuli in other plants. Additional genes, including genes of unknown function, were also identified, broadening our understanding of chitin-elicited responses. Among transcripts with enhanced accumulation, one cluster was enriched in genes with both the W-box promoter element and a novel regulatory element. In addition, a number of transcripts had decreased abundance, encoding several proteins involved in cell wall strengthening and wall deposition. The chalcone synthase promoter element was identified in the upstream regions of these genes, suggesting that pathogen signals may suppress the expression of some genes. These data indicate that Arabidopsis should be an excellent model to elucidate the mechanisms of chitin elicitation in plant defence. [source] Degranulation of Mast Cells Provokes a Massive Inflammatory Reaction in the Tympanic Membrane,THE LARYNGOSCOPE, Issue 7 2001Per Olof Eriksson MD Abstract Objective The pars flaccida is extremely rich in mast cells. On stimulation the mast cells release preformed and de novo synthesized inflammatory substances. The purpose of this study was to examine how these mast cell substances provoke inflammatory changes in the tympanic membrane. Study Design In vivo, murine model. Methods In a rat model, the mast cell secretagogue compound 48/80 was applied locally to the tympanic membrane on 4 consecutive days and the ensuing inflammatory changes were evaluated by otological, light, and electron microscopy 3, 6, 9, 12, 18, 24, 36, and 48 hours and 4, 6, and 8 days later. Results Degranulation of the mast cells occurred within 3 hours of applying compound 48/80. Release of the mast cell substances coincided with an inflammatory event characterized by a two-stage reaction: an edema stage, peaking 6 hours after application, followed by a massive invasion of inflammatory cells, peaking at 24 and 48 hours. Pars flaccida and pars tensa were both involved, pars flaccida showing the earliest changes. Pars tensa exhibited the same biphasic reaction as pars flaccida, but approximately 6 hours later. Conclusions The mast cells of the pars flaccida have the capacity to elicit an intense inflammation of the tympanic membrane. The biphasic reaction pattern resembles that observed in experimental otitis media, suggesting involvement of the mast cells in this inflammatory condition of the middle ear. [source] Molecular Changes in Normal Appearing White Matter in Multiple Sclerosis are Characteristic of Neuroprotective Mechanisms Against Hypoxic InsultBRAIN PATHOLOGY, Issue 4 2003Ursula Graumann Multiple sclerosis is a chronic inflammatory disease of the CNS leading to focal destruction of myelin, still the earliest changes that lead to lesion formation are not known. We have studied the geneexpression pattern of 12 samples of normal appearing white matter from 10 post-mortem MS brains. Microarray analysis revealed upregulation of genes involved in maintenance of cellular homeostasis, and in neural protective mechanisms known to be induced upon ischemic preconditioning. This is best illustrated by the upregulation of the transcription factors such as HIF-1, and associated PI3K/Akt signalling pathways, as well as the upregulation of their target genes such as VEGF receptor 1. In addition, a general neuroprotective reaction against oxidative stress is suggested. These molecular changes might reflect an adaptation of cells to the chronic progressive pathophysiology of MS. Alternatively, they might also indicate the activation of neural protective mechanisms allowing preservation of cellular and functional properties of the CNS. Our data introduce novel concepts of the molecular pathogenesis of MS with ischemic preconditioning as a major mechanism for neuroprotection. An increased understanding of the underlying mechanisms may lead to the development of new more specific treatment to protect resident cells and thus minimize progressive oligondendrocyte and axonal loss. [source] | |||||||||||||