I am Professor Emeritus having retired formally in 1993 and since then have held the Honorary Post of 'Visiting Professor' at King's College London, Guy's Campus. I have a lab and office space there and undertake electrophysiological-based experiments currently on mice and in particular the innervation of the tail
EphB receptors tyrosine kinases and ephrinB ligands were first identified as guidance molecules i... more EphB receptors tyrosine kinases and ephrinB ligands were first identified as guidance molecules involved in the establishment of topographical mapping and connectivity in the nervous system during development. Later in development and into adulthood their primary role would switch from guidance to activity-dependent modulation of synaptic efficacy.
Motoneurone disease (MND or amyotrophic lateral sclerosis) is a paralysing disease of unknown cau... more Motoneurone disease (MND or amyotrophic lateral sclerosis) is a paralysing disease of unknown cause involving progressive, widespread muscle atrophy due to degeneration of spinal and other motoneurones and an accompanying loss of Betz cells in the motor cortex. A current hypothesis attributes the disease to the loss of a muscle-derived neurotrophic factor acting in concert with the normal age-related deterioration and loss of motoneurones. The roots of this hypothesis are traced through research based mainly on the developing neuromuscular system, and in particular on the age-related processes of natural motoneurone death during embryogenesis: the neonatal reduction of polyneuronal innervation and the age-dependent variations in motor nerve terminal sprouting in response to partial denervation. A consideration of the disease process itself in association with the review of earlier work provide the background for the present work which reexamines ultrastructurally the chromatolytic and later responses to axotomy and the muscle-dependent factors responsible for the reformation of the Nissl bodies.
Alpha (greater than 40 microns) and gamma (less than 30 microns) motoneurons in inspiratory motor... more Alpha (greater than 40 microns) and gamma (less than 30 microns) motoneurons in inspiratory motor nuclei of the thoracic spinal cord of the adult cat were labelled retrogradely by the intramuscular injection of HRP. Small (less than 30 microns) unlabelled neurons within 200-300 microns of labelled motoneurons were analysed qualitatively and quantitatively with both the light and electron microscope. Most of these small unlabelled neurons had inconspicuous nucleoli, wrinkled nuclear membranes, low numbers of nuclear pores, and Nissl bodies which were either small or had the form of an amorphous perinuclear band. Such Nissl bodies were composed primarily of aggregates of polyribosomes within which short fragments of granular endoplasmic reticulum were distributed. Alpha and gamma motoneurons in contrast had prominent nucleoli, smooth-contoured nuclei, more nuclear pores and large, discrete Nissl bodies. Such Nissl bodies were composed primarily of several lamellae of granular endoplas...
The effects of sustained constriction of the rib cage (RCC), constriction of the abdomen (AC) and... more The effects of sustained constriction of the rib cage (RCC), constriction of the abdomen (AC) and of breathing against a positive pressure of 10 cms of water (PPB) were studied in four normal subjects with moderate constant hypercapnia. Intercostal electrical activity (Eic) was measured by implanted wire electrodes and diaphragmatic electrical activity (Edia) by oesophageal electrodes. There was no fixed relation between Edia and VT. VT was unaltered during AC and RCC: Edia was unaltered during AC but increased during RCC. The response to PPB without constriction varied: three subjects increased end-expiratory VL with increase in Edia and inspiratory Eic. One subject initially, and one subject after training, maintained end-expiratory VL constant with no change in Edia and an increase in expiratory Eic. When PPB was applied during AC and RCC there was an increase in Edia proportional to end-expiratory lung volume. The overall response to distortion was determined by voluntary choice...
EphB receptors tyrosine kinases and ephrinB ligands were first identified as guidance molecules i... more EphB receptors tyrosine kinases and ephrinB ligands were first identified as guidance molecules involved in the establishment of topographical mapping and connectivity in the nervous system during development. Later in development and into adulthood their primary role would switch from guidance to activity-dependent modulation of synaptic efficacy.
Motoneurone disease (MND or amyotrophic lateral sclerosis) is a paralysing disease of unknown cau... more Motoneurone disease (MND or amyotrophic lateral sclerosis) is a paralysing disease of unknown cause involving progressive, widespread muscle atrophy due to degeneration of spinal and other motoneurones and an accompanying loss of Betz cells in the motor cortex. A current hypothesis attributes the disease to the loss of a muscle-derived neurotrophic factor acting in concert with the normal age-related deterioration and loss of motoneurones. The roots of this hypothesis are traced through research based mainly on the developing neuromuscular system, and in particular on the age-related processes of natural motoneurone death during embryogenesis: the neonatal reduction of polyneuronal innervation and the age-dependent variations in motor nerve terminal sprouting in response to partial denervation. A consideration of the disease process itself in association with the review of earlier work provide the background for the present work which reexamines ultrastructurally the chromatolytic and later responses to axotomy and the muscle-dependent factors responsible for the reformation of the Nissl bodies.
Alpha (greater than 40 microns) and gamma (less than 30 microns) motoneurons in inspiratory motor... more Alpha (greater than 40 microns) and gamma (less than 30 microns) motoneurons in inspiratory motor nuclei of the thoracic spinal cord of the adult cat were labelled retrogradely by the intramuscular injection of HRP. Small (less than 30 microns) unlabelled neurons within 200-300 microns of labelled motoneurons were analysed qualitatively and quantitatively with both the light and electron microscope. Most of these small unlabelled neurons had inconspicuous nucleoli, wrinkled nuclear membranes, low numbers of nuclear pores, and Nissl bodies which were either small or had the form of an amorphous perinuclear band. Such Nissl bodies were composed primarily of aggregates of polyribosomes within which short fragments of granular endoplasmic reticulum were distributed. Alpha and gamma motoneurons in contrast had prominent nucleoli, smooth-contoured nuclei, more nuclear pores and large, discrete Nissl bodies. Such Nissl bodies were composed primarily of several lamellae of granular endoplas...
The effects of sustained constriction of the rib cage (RCC), constriction of the abdomen (AC) and... more The effects of sustained constriction of the rib cage (RCC), constriction of the abdomen (AC) and of breathing against a positive pressure of 10 cms of water (PPB) were studied in four normal subjects with moderate constant hypercapnia. Intercostal electrical activity (Eic) was measured by implanted wire electrodes and diaphragmatic electrical activity (Edia) by oesophageal electrodes. There was no fixed relation between Edia and VT. VT was unaltered during AC and RCC: Edia was unaltered during AC but increased during RCC. The response to PPB without constriction varied: three subjects increased end-expiratory VL with increase in Edia and inspiratory Eic. One subject initially, and one subject after training, maintained end-expiratory VL constant with no change in Edia and an increase in expiratory Eic. When PPB was applied during AC and RCC there was an increase in Edia proportional to end-expiratory lung volume. The overall response to distortion was determined by voluntary choice...
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Papers by Thomas A Sears