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Biomedical subjects

C Woolf

Publications and source records attributed to C Woolf.

9 recordsLinked to original sources

Influence of inflammation or disconnection from peripheral target tissue on the capsaicin sensitivity of rat dorsal root ganglion sensory neurones.

Dorsal root ganglion (DRG) sensory neurones from adult rats are known to lose their capsaicin sensitivity in vitro if they are cultured without nerve growth factor (NGF). Here we show similar results following peripheral nerve transection in vivo, which deprives DRG sensory neurones of target-derived NGF. By measuring capsaicin-stimulated 45Ca uptake into DRG neurones which had been briefly cultured, capsaicin sensitivity was shown to decrease in neurones whose axons had been previously severed in vivo. Conversely, during experimental inflammation of the rat paw, there is an increase in the supply of NGF to neurones innervating the inflamed area. In this case, however, no significant increase in capsaicin sensitivity could be demonstrated in briefly cultured neurones which had previously innervated an inflamed limb. This suggests that expression of capsaicin sensitivity in DRG is maximal at levels of NGF found in normal animals.

Animals↗

Expression of a developmentally regulated, phosphorylated isoform of microtubule-associated protein 1B in regenerating axons of the sciatic nerve.

Monoclonal antibodies SMI-31 and 150 recognize phosphorylation epitopes on microtubule-associated protein 1B that have been shown to be developmentally down-regulated in the nervous system. We have used these antibodies to establish changes in the pattern of expression of their epitopes on microtubule-associated protein 1B in regenerating axons of the sciatic nerves in the adult mouse and rat. Immunohistochemical studies showed that, in the sciatic nerve, regenerating axons in both adult mice and rats were labelled with monoclonal antibody 150 in a proximodistal gradient which was highest at the growth cone. This is the first report of expression of a developmentally regulated, phosphorylated isoform of microtubule-associated protein 1B in regenerating axons. Immunoblotting showed that the expression of the isoform recognized by monoclonal antibody 150 is present in normal adult mouse sciatic nerve and in regenerating axons following crush or cut lesions, but was not detectable in the normal or regenerating adult rat peripheral nervous system. Regenerating axons were also labelled by monoclonal antibody SMI-31, but the labelling, unlike antibody 150 labelling, was uniform along the entire length of the axon and immunoblotting showed that it was due to recognition of neurofilament protein. We conclude that the phosphorylated isoforms of microtubule-associated protein 1B recognized by monoclonal antibody 150 that are developmentally down-regulated in the adult rat central and peripheral nervous systems and adult mouse cerebellum are maintained in the normal peripheral nervous system of the adult mouse. When peripheral axons regenerate in the adult mouse, the regenerating axons also contain these isoforms. Adult rat regenerating axons are stained by antibody 150 only in tissue sections, not in immunoblots. The maintenance of immature isoforms of microtubule-associated protein 1B in mouse peripheral axons may relate to a continual capacity for growth and remodelling. The immunohistochemical localization of the antibody 150 epitope in growth cone-like structures and sprouts in injured nerves shows that phosphorylation of microtubule-associated protein 1B is likely to be an integral part of the regenerative response. These results also show that the phosphorylation epitopes on microtubule-associated protein 1B recognized by monoclonal antibodies 150 and SMI-31 are different and that only expression of the former correlates with axonal regeneration.

Animals↗

Apneustic breathing provoked by limbic influences.

We describe a 64-year-old man with cerebrovascular disease who had an acute stroke characterised by pseudobulbar palsy, facial weakness, and pyramidal signs. He developed frequent emotional outbursts followed by periods of apneusis. Between these episodes he breathed with a regular and unvarying rate and tidal volume. Autopsy showed extensive cortical, subcortical and pontine infarction. The respiratory pattern indicated a dissociation between voluntary and automatic pathways. The descending limbic pathways were preserved but an abnormal pattern of automatic breathing (ie, apneusis) occurred because of the presence of bilateral pontine infarction.

Acute Disease↗

Neurotoxic damage evokes regenerative responses from adult rat sensory neurones.

When adult rats were pre-treated systemically with the excitotoxin, capsaicin, a subset of their dorsal root ganglion (DRG) sensory neurones responded as if they had been axotomised. Firstly, an increased proportion of capsaicin-sensitive DRG neurones (identified by using a cobalt stain) vigorously extended processes in vitro. Additionally, a subset of small dorsal root ganglion neurones expressed elevated levels of the growth-associated protein-43 (GAP-43) in situ. Both vigorous neuritogenesis and elevated GAP-43 levels are characteristics of neurones that are actively regenerating following mechanical damage. Although capsaicin-treated adult DRG neurones show these regenerative responses, their C-fibers fail to regenerate in vivo.

Animals↗

Substance P and calcitonin gene-related peptide synergistically modulate the gain of the nociceptive flexor withdrawal reflex in the rat.

A comparison has been made between the effects of intrathecally administered L-glutamate, L-aspartate, substance P and calcitonin gene-related peptide (CGRP) on the excitability of rat flexor alpha-motoneurons activated monosynaptically by Ia afferents and polysynaptically by high mechano-threshold cutaneous afferents. At doses that do not modify the monosynaptic reflex, substance P, CGRP and some factor released from sural C-fibres increase the excitability of the nociceptive flexion reflex for prolonged periods in a multiplicative fashion. The excitatory amino acids have no such action. We suggest that one role for C-afferent neuropeptides is a long-acting gain modulation of nociceptive inputs into the spinal cord.

Animals↗

Pharyngoesophageal dysphagia and gastroesophageal reflux.

Pharyngoesophageal dysphagia occurred in 51.3 percent of 1,000 consecutive patients with gastroesophageal reflux. Aspiration, secondary to food obstruction, occurred in 30 percent of these patients, and some developed significant secondary respiratory symptoms. The site of obstruction was localized to the cricopharyngeus by timing the interval from swallow to obstruction. Cricopharyngeal incoordination was demonstrated in 20 of 52 patients studied by high speed esophageal manometry. Surgical correction of gastroesophageal reflux in patients with intractable reflux symptoms was shown to be effective in relieving pharyngoesophageal dysphagia in all but a small number of patients with very severe symptoms. In those with persistent dysphagia cricopharyngeal myotomy at a later stage was effective in giving relief.

Deglutition Disorders↗