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John D England

Publications and source records attributed to John D England.

10 recordsLinked to original sources
PubMed2005

Serial electrophysiologic studies in rhesus monkeys with Krabbe disease.

Krabbe disease is a progressive leukodystrophy that results in demyelination in the central and peripheral nervous systems in humans. It has been described in a number of mammalian species including the rhesus monkey. We performed serial nerve conduction studies beginning within the first 2 months of life in four homozygous, two heterozygous, and two normal rhesus monkeys (Macaca mulatta) to characterize the peripheral neuropathy. Mean conduction velocities of the median, ulnar, and tibial nerves were significantly slower in the affected than unaffected monkeys at all ages (P < 0.0001). The conduction velocity differences became more apparent between the affected and unaffected as the monkeys aged. When compared to the unaffected monkeys, the serial conduction velocities suggested occurrence of dysmyelination followed by demyelination in the affected monkeys. These observations provide further insight into the disease process and suggest an early window of opportunity for treating Krabbe disease.

Action Potentials↗
PubMed2005

Distal symmetrical polyneuropathy: a definition for clinical research. A report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation.

The objective of this report was to develop a case definition of "distal symmetrical polyneuropathy" to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetrical polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

Electrodiagnosis↗
PubMed2004

Ibuprofen blocks changes in Na v 1.7 and 1.8 sodium channels associated with complete Freund's adjuvant-induced inflammation in rat.

UNLABELLED: Although nerve growth factor plays a role in augmenting sodium channel expression in small dorsal root ganglion (DRG) cells, the cytochemical mediators responsible for enhanced expression in large DRG neurons are unknown. To narrow the search for mediators involved in the increased production of sodium channels in large DRG neurons, we examined the effect of cyclooxygenase inhibition on sodium channel production during inflammation. Thirty minutes before the subcutaneous injection of complete Freund's adjuvant (CFA), rats received ibuprofen (nonselective, cyclooxygenase inhibitor), NS-398 (selective, cyclooxygenase inhibitor), or vehicle. Withdrawal thresholds from thermal and mechanical stimulation were measured before and immediately after CFA injection and at selected hourly intervals after injection for the next 24 hours. Sodium channel up-regulation was then examined in DRG by using site-specific, anti-sodium channel antibodies, Na(v) 1.7 and 1.8. Both ibuprofen and NS-398 provided analgesia during the second phase of inflammatory hyperalgesia that begins 3 hours after CFA injection. The up-regulation, predominantly of Na(v) 1.7 and minimally of Na(v) 1.8 channels, seen in vehicle-treated rats was suppressed by both drugs at 24 hours after injection. By 72 hours after injection, no difference in labeling between the drug- and vehicle-treated animals was observed. Sodium channel labeling in large DRG neurons returned to baseline between 1 and 2 weeks after CFA injection, whereas small cell labeling persisted. The cytochemical signal for sodium channel up-regulation in the large DRG cells that most closely correlates with inflammatory hyperalgesia is mediated at least in part through products of the cyclooxygenase pathway. PERSPECTIVE: Expression of sodium channels in dorsal root ganglia increases dramatically during inflammation. The increase in sodium channels is thought to enhance neuronal excitability and to play a role in hyperalgesia and wound vigilance during healing. We provide evidence that prostaglandins play a role in signaling channel augmentation.

Animals↗
PubMed2004

Charcot-Marie-Tooth disease: electrophysiology, molecular genetics and clinical management.

Over the past decade there has been a huge increase in the understanding of the molecular basis of Charcot-Marie-Tooth disease (CMT). Additionally there has been a better delineation of the neurophysiological deficits and clinical problems associated with CMT. This paper reviews the current molecular basis of CMT and the electrophysiological, clinical and phenotypical characteristics of the various subtypes, followed by a discussion of novel and promising therapeutic interventions that potentially could be used as part of a treatment regimen for CMT. These interventions may involve attempts to slow down or stop neurodegenerative processes through nerve growth factors, limiting oxidative stress by using antioxidants, or normalizing gene expression through genetic manipulation. Other potential therapeutic target areas include the progesterone receptor on myelin-forming Schwann cells, the immune system via modulation of nerve inflammation, and enhancing glutathione transferase activity. While ongoing molecular research continues to identify more of the mutant genes and proteins that cause the various disease subtypes, the focus of clinical research should continue to be on developing pharmaceutical and rehabilitative therapies to reverse nerve degeneration and ultimately improve the functioning of people with CMT.

Animals↗
PubMed2003

Electrodiagnostic evaluation of hereditary motor and sensory neuropathies.

Electrodiagnosis can classify hereditary motor and sensory neuropathies (HMSN) into two basic types: primarily demyelinating with secondary axonal loss and primarily axonal. For the most part, the various forms of HMSN show uniform symmetric nerve conduction slowing, in contrast to acquired neuropathies, which may be multifocal with nonuniform conduction velocity slowing and temporal dispersion. Nevertheless, there are exceptions. This article reviews the available literature and describes the electrodiagnostic approach to HMSN, detailing potential sources of error that can lead to misinterpretation of data.

Electrodiagnosis↗
PubMed2002

Ankyrin G and voltage gated sodium channels colocalize in human neuroma--key proteins of membrane remodeling after axonal injury.

We tested if ankyrin G could be detected in human neuroma, if it colocalized with site-specific peripheral nerve sodium channels that accumulate at axon tips of injured nerve, and if there are differences in the distribution of these proteins in non-painful neuroma and painful neuroma tissue vs. normal nerve. Frozen sections from one painful, six non-painful, and three normal nerves were immunocytochemically examined. A double labeling technique with highly specific antibodies against peripheral nerve type 1 (Na(v)1.7), and peripheral nerve type 3 (Na(v)1.8) sodium channels and anti-ankyrin G antibodies detected sodium channels and ankyrin G on the same section, using confocal laser scanning microscopy. Ankyrin G colocalized with both types of sodium channels. Neuroma specimens exhibited considerably larger immunofluorescence for both sodium channels and ankyrin G compared with normal nerve. The painful neuroma presented an even more pronounced immunolabeling in clusters. Findings support results from animal models that link ankyrin G with clustering of sodium channels at axon tips of unmyelinated, sprouting fibers. A common (repair-) mechanism that exists throughout the human nervous system for clustering sodium channels at a high density is assumed. A dysregulation in this membrane remodeling mechanism might be an initial step in a cascade that leads to a painful rather than a non-painful neuroma.

Ankyrins↗
PubMed2002

Painful neuromas: a potential role for a structural transmembrane protein, ankyrin G.

OBJECT: Severe nerve injury induces the formation of a neuroma. Some neuromas cause excruciating pain. Overexpression of Na+ channels leads to hyperexcitability and painful phenomena. Ankyrin G, a multifunctional transmembrane protein of the axolemma, might be a key protein in neuroma formation because it binds Na+ channels in the initial segments of a regenerating axon and links with neuronal cell adhesion molecules. The authors wanted to determine if ankyrin G could be detected in neuroma, and if present, whether there would be differences in distribution between nonpainful neuromas, painful neuromas, and normal nerve. METHODS: First, frozen sections of nine nerve specimens obtained from six patients (six nonpainful neuromas, one painful neuroma, and two normal nerves) were immunocytochemically screened for ankyrin G by using confocal laser scanning microscopy. Second, specimens from 29 patients (seven painful neuromas, 15 nonpainful neuromas, and seven normal nerves) were examined using immunoblot analysis for their ankyrin G content. Western blot analysis detected ankyrin G, which was visualized by applying the enhanced chemiluminescence technique. Computerized densitometry was used to quantitate ankyrin G expression by comparing band intensities. Normal nerve served as control. Neurofilament was used as a marker for nerve tissue content. Ankyrin G could be detected and was found to be increased in neuromas. The mean band intensity values were 1838 for painful neuromas, 1166 for nonpainful neuromas, and 411 for normal nerves. In two cases the authors were able to compare specimens of painful neuroma and normal nerve from the same patient. The painful neuromas exhibited considerably higher levels of ankyrin G. Painful neuroma and normal nerve densitometry values were 499 and 165, respectively, for one patient, and 4254 and 821, respectively, for the other patient. Painful neuromas were also found to have higher neurofilament values than nonpainful neuromas. CONCLUSIONS: Altered regulation of ankyrin G after nerve injury may lead to hyperexcitability and painful phenomena via clustering of Na+ channels. A propensity to overexpress ankyrin G after peripheral nerve trauma may turn out to be a factor in the development of painful neuromas and neuropathic pain. The relevant literature regarding the importance of ankyrin G for nerve regeneration and nerve membrane remodeling is reviewed.

Adult↗
PubMed2002

Neuropathic pain.

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Analgesics↗