4-Aminopyridine and 3,4-diaminopyridine were evaluated for their abilities to delay the onset of paralysis due to botulinum neurotoxin types A, B, and E. Experiments were done on phrenic nerve-hemidiaphragm preparations excised from mice. At a concentration that produced an enhancement in muscle twitch amplitude, 4-aminopyridine and 3,4-diaminopyridine delayed the onset of paralysis due to botu...

In the course of some experiments with tetanus toxin it was noted that cysteine, when added to the toxin with the intention of preserving it from oxidation, had, on the contrary, a deleterious effect. Other experiments showed that on diphtheria toxin there was but little effect, and on botulinus toxin and on ricin none at all. Locke and Maint have mentioned that cysteine can play a role in toxi...

Regulation of myelination by oligodendrocytes in the CNS has important consequences for higher-order nervous system function (e.g., [1-4]), and there is growing consensus that neuronal activity regulates CNS myelination (e.g., [5-9]) through local axon-oligodendrocyte synaptic-vesicle-release-mediated signaling [10-12]. Recent analyses have indicated that myelination along axons of distinct neu...

Using a novel assay based on the sorting and transport of a fluorescent fragment of tetanus toxin, we have investigated the cytoskeletal and motor requirements of axonal retrograde transport in living mammalian motor neurons. This essential process ensures the movement of neurotrophins and organelles from the periphery to the cell body and is crucial for neuronal survival. Unlike what is observ...

The dentate gyrus is thought to be a key area in containing the spread of seizure discharges in temporal lobe epilepsy. We investigated whether it actively contributes to the transition to seizure in vivo using the tetanus toxin chronic experimental epilepsy. Brief epileptic discharges lasted <2 s in freely moving animals and were clearly distinguishable from spontaneous seizures that lasted te...

Synaptic core complex formation is an essential step in exocytosis, and assembly into a superhelical structure may drive synaptic vesicle fusion. To ascertain how Ca(2+) could regulate this process, we examined calmodulin binding to recombinant core complex components. Surface plasmon resonance and pull-down assays revealed Ca(2+)-dependent calmodulin binding (K(d) = 500 nM) to glutathione S-tr...

Tetanus neurotoxin (TeNT) consists of two protein chains connected by a disulfide linkage: The heavy chain mediates the toxin binding and uptake by neurons, whereas the light chain cleaves synaptobrevin and thus blocks neurotransmitter release.Chemically inactivated TeNT (tetanus toxoid) is utilized for the production of tetanus vaccines. For safety reasons, each toxoid bulk has to be tested fo...

Cephalic tetanus is a localized form of tetanus. As in generalized forms, trismus is a prominent feature of the disease, leading to considerable difficulty in feeding, swallowing of the saliva and mouth hygiene. These difficulties often precede respiratory problems and aspiration bronchopneumonia is a frequent life-threatening complication. Muscle relaxants other than curare drugs may show a li...

The present study attempted to evaluate whether soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate lysosome fusion in response to death receptor activation and contribute to membrane raft (MR) clustering and consequent endothelial dysfunction in coronary arterial endothelial cells. By immunohistochemical analysis, vesicle-associated membrane proteins 2 (VAMP...

By integrating photopolymerized cross-linked polyacrylamide gels within a microfluidic device, we have developed a microanalytical platform for performing electrophoresis-based immunoassays. The microfluidic immunoassays are performed by gel electrophoretic separation and quantitation of bound and unbound antibody or antigen. To retain biological activity of proteins and maintain intact immune ...