ANTHONY JOHN WINDEBANK

..It leads to orderly disassembly of the cell. Advances in understanding of the pathways from specific disease to neuronal death are leading to new strategies designed to prevent death and treat diseases of the nervous system...

..The mechanisms underlying painful platinum-induced neuropathy remain poorly understood. Previous studies have demonstrated important roles for TRPV1, TRPM8, and TRPA1 in inflammation and nerve injury induced pain...

..Thirty to forty percent of cancer patients receiving these agents develop pain and sensory loss. Oxaliplatin induces distinctive cold-associated dysesthesias in up to 80% of patients...

..A better understanding of cellular mechanisms will lead to novel treatment strategies that will protect neurons without decreasing therapeutic efficacy...

..Analysis of secondary endpoints and a global impression of improvement by patients and physicians did not show consistent differences between the groups. IGF-I was safe, but did not improve symptoms in this 6-month trial...

..In patients with neuropathy, restorative approaches have not been well established. Symptomatic and other management are necessary to maintain and improve quality of life...

..We conclude that it is possible to conduct minimally invasive electrophysiologic testing in rat forelimbs. The CMAP is a valid parameter that shows the typical time course of nerve regeneration and reinnervation...

..There was no association between symptoms of late deterioration and magnitude of decline. Rather, the presence of these symptoms was associated with the magnitude of the residual deficits...

..representing increasing impairment based on the judgment of percentage abnormality with corrections made for age, sex, physical fitness, and physical characteristics...

..In addition, disproportionate platinum accumulation may explain why a drug aimed at killing rapidly dividing cells causes sensory neurotoxicity...

..Of these two models of neuron loss, the proportional loss of motor neurons was a better fit of the data than a linear loss...

..These findings confirm the clinical relevance of MUNE as an outcome measure in the motor neuron diseases and provide further validation for its use in clinical trial research...

..These mutations were not found in North American kindreds with H-BPN with a conserved 500-kilobase sequence of DNA at the 17q25 chromosomal region (where SEPT9 localizes) where a founder mutation has been suggested...

..This demonstrates for the first time that cisplatin does not signal for death via the fas pathway, but it does initiate the mitochondrial stress pathway in neurons and that NGF blocks death upstream of bax redistribution...

..It is likely that DLRPN and LRPN are immune-mediated neuropathies that should be separated from chronic inflammatory demyelinating polyneuropathy and from systemic necrotizing vasculitis...

..There was an association with reported weakness and initial deficits. There was a slow decline in MUNE values over time in both groups...

..Our results demonstrate that both compounds cause apoptosis of DRG neurons but compared to cisplatin, oxaliplatin forms fewer Pt-DNA adducts and is less neurotoxic to DRG neurons in vitro...

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..CONCLUSIONS: This model provides a novel means for studying the pathogenesis and treatment of early stages of diabetic neuropathy...

..Additionally, we investigated the effect of CPT-11 on oxaliplatin pharmacokinetics...

..We present work that demonstrates that cisplatin reacts rapidly with dimethyl sulfoxide (DMSO) in solution and identify the structure and reactivity of the resulting compound...

..Axon regeneration was demonstrated by three-dimensional reconstruction of serial histological sections...

..Further, these multichannel biodegradable polymer scaffolds effectively serve as platforms for quantitative analysis of axonal regeneration...

..Optimization of this scaffold environment establishes a platform for future studies of the effects of cell types, trophic factors or pharmacological agents on the regenerative capacity of the injured spinal cord...

..NGF protects DRG from this toxin by upregulating antioxidants such as catalase, GPx and GSH...

..The results of this study can be used as basis for developing new nerve repair techniques that may improve the accuracy of regeneration...

..Cell cycle disruption was examined by cyclin D1 expression. Neuronal death was associated with up-regulation of markers associated with DNA damage and aberrant entry into G1 of the cell cycle...

..These results suggest that PLGA/PEG microparticles are useful as delivery vehicles for controlled release of ODNs and merit further investigation in cell culture and animal models of glioblastoma...

..The objective of this study was to examine the surgical methods that may be used to assess the factors that influence the level of scar and cystic formation in SCI...

..Structural support of axonal regeneration is combined with integrated polymeric and cellular delivery systems for therapeutic drugs and for neurotrophic molecules to regionalize growth of specific nerve populations...

..Moreover, we look at the Cutter and Wyeth incidents after the vaccine's approval and the errors that led to them...

..The pattern of myelination, with extracellular collagen and basal lamina, was characteristic of SC myelination. Our results show that FB labeling is an effective way to measure the origin of regenerating axons...

..Primary and reversible toxic events involve destabilization of microtubules mediated by full-length mhtt before cleavage. Restoration of microtubule structure by taxol inhibits nuclear entry and increases cell survival...

..Vitamin E may play an important role. Use of a serum-free medium may be beneficial for in vitro myelination studies because serum has unknown inhibitory effects...

..A controlled study to evaluate a new technique for spinal rod fixation after spinal cord injury in rats. Alignment of implanted tissue-engineered scaffolds was assessed radiographically and by magnetic resonance imaging...

..These findings suggest that charged OPF hydrogels are capable of sustaining both primary nerve cells and the neural support cells that are critical for regeneration...

..Our results suggest that this novel copolymer, PCLF, is an injectable, self-cross-linkable, and biocompatible macromer that may be potentially used as a scaffold for tissue engineering applications...

..Downstream signaling showed sustained hyperphosphorylation of MAPK (Erk(1-2)) but not of SNT or Akt. High-dose NGF may induce cytoplasmic relocation of the receptor TrkA and axonal growth arrest independently of p75NTR...

..The methods presented in this study can be used as a basis for optimizing these properties for future, possibly clinical, application...

..In vitro studies using PC12 cells and DRG show PCLF-PPy materials synthesized with NSA or DBSA support cell attachment, proliferation, neurite extension, and are promising materials for future studies involving electrical stimulation...

..These findings offer a potential therapeutic strategy in the control of human GBM cell line growth in vitro and suggest that PLGA microparticles may be appropriate as delivery vehicles for the "decoy" ODN strategy...

..2D digital video ankle motion analysis is a practical and sensitive method to assess function in the rat sciatic nerve model...

..We also present the concept of the multichannel nerve tube that may limit dispersion by separately guiding groups of regenerating axons...

..2D digital video motion analysis can be used to quantify movement of the wrist and the MP joint in rats. It is a valid method to evaluate functional deficit and recovery after nerve injury and repair in the forelimb...

..02). Mean time from symptom onset to diagnosis was 13 months. Neither survival nor time to diagnosis changed significantly over time...

..We have previously observed that genetic deletion of the CD8+ T cell effector molecule perforin leads to preservation of motor function and preservation of spinal axons in chronically demyelinated mice...

..In addition, the role of mechanical properties such as surface stiffness in modulating cell responses has been emphasized using this model blend system...

..After 24h, 1 microM methylmercury increased both DNA end-labeling (P<0.01) and nuclear fragmentation (P<0.02). The latter effect appeared to be dose-dependent...

..They are autologous, may be genetically modified to express neurotrophins, and are compatible with polymer surfaces that may be used as a potential delivery system...

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..The goal is to develop a mechanism-based therapy that will prevent the major dose-limiting side effect of the platinum compounds. ..

..Imaging with Micro-CT and MR microscopy will be combined with histological and functional assessments to measure success in promoting regeneration. ..

..We will also determine whether the effects of NGF are shared by the other DRG growth factors, brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3). ..

..The goal is to develop a mechanism-based therapy that will prevent the major dose-limiting side effect of the platinum compounds. ..