Exploring use of incorrect terminology used in medical sciences: quest for scientific and academic verity

Scientific terminology is used in the context of academic and clinical settings and scientists create novel terms to name them. Many of such terms used in basic and clinical sciences nevertheless appear flawed, and have remained unexamined for a long period of time. Due to common usage, such inappropriate terms have gradually become part of the common language of medical science and continue to be in use. Terms should reflect scientific brevity, be self-explanatory, overcome ambiguity, provide for universal usage, and help basic science to integrate better with the clinical domain logically, correctly and practically. Despite existing efforts in standardization, a large number of non-conforming terms appear to remain in medical use. Some of these are carried on from older terminology, and others are simply the result of convenient habits and usage albeit their logical inconsistency. Words with well-known meaning in common language often pose an academic challenge due to inconsistencies in nomenclature. This study which is the first of its kind, aims at questioning a plethora of terms currently being used in the disciplines of Anatomy, Radiology, Medicine and Surgery that are inappropriate, both logically as well as scientifically, and recommends that these be dropped from the inventory of terms used in medical sciences, and replaced with terminology presented in this article that are semantically logical, scientifically valid, as well as practical. Keywords: Medical terminology, Anatomical terminology DOI: 10.7176/JEP/10-6-19

Imaging of myelin proteins during injury and differentiation

Myelin injury plays a role in many devastating conditions, including multiple sclerosis, and neuromyelitis optica. Previous work in understanding myelin injury has utilised a combination of high-resolution static imaging modalities, such as electron microscopy, and ensemble-averaged imaging, such as immunohistochemistry. Within the work presented in this thesis the behaviour of myelin basic protein was addressed, during various stages of differentiation and injury. In order to explore this several reporters for myelin basic protein were designed and encoded within Semliki forest constructs in order to induce protein transduction in oligodendroglial cells. Reporters utilised several fluorescent tags including Dendra2, mCherry, and GFP. These viral vectors were characterised to determine the expression kinetics and toxicity within cells. Following the production of the MBP reporters, a complement injury modality was optimised to induce myelin/oligodendrocyte specific injury with little injury within axons/neurones. This myelin injury was utilised for live imaging of myelin using the MBP reporters produced previously. The reporters produced were utilised to explore the change in particle dynamics following myelin injury, using single molecule TIRF imaging. Responses to injury were compared over various stages of oligodendrocyte differentiation, where it was found that MBP dynamics following injury varied most when mature oligodendrocytes were injured

GBS100: Celebrating a Century of Progress in Guillain-Barré Syndrome

No abstract available

The “Lillie Transition”: Models of the Onset of Saltatory Conduction in Myelinating Axons

Almost 90 years ago, Lillie reported that rapid saltatory conduction arose in an iron wire model of nerve impulse propagation when he covered the wire with insulating sections of glass tubing equivalent to myelinated internodes. This led to his suggestion of a similar mechanism explaining rapid conduction in myelinated nerve. In both their evolution and their development, myelinating axons must make a similar transition between continuous and saltatory conduction. Achieving a smooth transition is a potential challenge that we examined in computer models simulating a segmented insulating sheath surrounding an axon having Hodgkin-Huxley squid parameters. With a wide gap under the sheath, conduction was continuous. As the gap was reduced, conduction initially slowed, owing to the increased extra-axonal resistance, then increased (the “rise”) up to several times that of the unmyelinated fiber, as saltatory conduction set in. The conduction velocity slowdown was little affected by the number of myelin layers or modest changes in the size of the “node,” but strongly affected by the size of the “internode” and axon diameter. The steepness of the rise of rapid conduction was greatly affected by the number of myelin layers, and axon diameter, variably affected by internode length and little affected by node length. The transition to saltatory conduction occurred at surprisingly wide gaps and the improvement in conduction speed persisted to surprisingly small gaps. The study demonstrates that the specialized paranodal seals between myelin and axon, and indeed even the clustering of sodium channels at the nodes, are not necessary for saltatory conduction

Microglial glutathione and glutamate: regulation mechanisms

Microglia, the immune cells of the central nervous system (CNS), are important in the protection of the CNS, but may be implicated in the pathogenesis of neuroinflammatory disease. Upon activation, microglia produce reactive oxygen and nitrogen species; intracellular antioxidants are therefore likely to be important in their self-defence. Here, it was confirmed that cultured microglia contain high levels of glutathione, the predominant intracellular antioxidant in mammalian cells. The activation of microglia with lipopolysaccharide (LPS) or LPS + interferon-gamma was shown to affect their glutathione levels. GSH levels in primary microglia and those of the BV-2 cell line increased upon activation, whilst levels in N9 microglial cells decreased. Microglial glutathione synthesis is dependent upon cystine uptake via the xc- transporter, which exchanges cystine and glutamate. Glutamate is an excitatory neurotransmitter whose extracellular concentration is tightly regulated by excitatory amino acid transporters, as high levels cause toxicity to neurones and other CNS cell types through overstimulation of glutamate receptors or by causing reversal of xc- transporters. Following exposure to LPS, increased extracellular glutamate and increased levels of messenger ribonucleic acid (mRNA) for xCT, the specific subunit of xc-, were observed in BV-2 and primary microglial cells, suggesting upregulated GSH synthesis. An activation-induced decrease in N9 GSH levels suggests that this cell line is more susceptible to oxidative damage, and may be less able to upregulate GSH synthesis. Albumin, to which microglia may be exposed following blood-brain barrier damage, increased iNOS expression, glutamate release, xCT mRNA levels and intracellular levels of GSH and ATP in BV-2 and primary microglia. Primary and BV-2 microglial conditioned medium contained low levels of GSH, suggesting that microglia may release GSH. Modulation of microglial metabotropic glutamate receptors (mGluRs) may alter microglial activation and neurotoxicity. Here, stimulation of the neuroprotective mGluR5 and group III mGluRs caused a decline in GSH levels in BV-2 and N9 microglia, respectively. In contrast mGluR1 stimulation may increase BV-2 GSH levels. The work presented in this thesis therefore extends current knowledge regarding microglial GSH and its regulation, and contributes to the understanding of microglial neurotoxicity and neuroprotection