Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions

Substance P (SP) play a central role in nociceptive transmission and it is an agonist of the Neurokinin-1 receptor located in the lamina I of the spinal cord. SP is a major proteolytic product of the protachykinin-1 primarily synthesized in neurons. Proprotein convertases (PCs) are extensively expressed in the central nervous system (CNS) and specifically cleave at C-terminal of either a pair of basic amino acids, or a single basic residue. The proteolysis control of endogenous protachykinins has a profound impact on pain perception and the role of PCs remain unclear. The objective of this study was to decipher the role of PC1 and PC2 in the proteolysis surrogate protachykinins (i.e. Tachykinin 20-68 and Tachykinin 58-78) using cellular fractions of spinal cords from wild type (WT), PC1-/+ and PC2-/+ animals and mass spectrometry. Full-length Tachykinin 20-68 and Tachykinin 58-78 was incubated for 30 minutes in WT, PC1-/+ and PC2-/+ mouse spinal cord S9 fractions and specific C-terminal peptide fragments were identified and quantified by mass spectrometry. The results clearly demonstrate that both PC1 and PC2 mediate the formation of SP and Tachykinin 58-71, an important SP precursor, with over 50% reduction of the rate of formation in mutant PC 1 and PC2 mouse S9 spinal cord fractions. The results obtained revealed that PC1 and PC2 are involved in the C-terminal processing of protachykinin peptides and suggest a major role in the maturation of the protachykinin-1 protein.

Characterization of Endoproteolytic Processing of Dynorphins by Proprotein Convertases using Mouse Spinal Cord S9 Fractions and Mass Spectrometry

Dynorphins are important neuropeptides with a central role in nociception and pain alleviation. Many mechanisms regulate endogenous dynorphin concentrations, including proteolysis. Proprotein convertases (PCs) are widely expressed in the central nervous system and specifically cleave at C-terminal of either a pair of basic amino acids, or a single basic residue. The proteolysis control of endogenous Big Dynorphin (BDyn) and Dynorphin A (Dyn A) levels has a profound impact on pain perception and the role of PCs remain unclear. The objective of this study was to decipher the role of PC1 and PC2 in the proteolysis control of BDyn and Dyn A levels using cellular fractions of spinal cords from wild type (WT), PC1-/+ and PC2-/+ animals and mass spectrometry. Our results clearly demonstrate that both PC1 and PC2 are involved in the proteolysis regulation of BDyn and Dyn A with a more important role for PC1. C-terminal processing of BDyn generates specific peptide fragments Dynorphin 1-19, Dynorphin 1-13, Dynorphin 1-11 and Dynorphin 1-7 and C-terminal processing of Dyn A generates Dynorphin 1-13, Dynorphin 1-11 and Dynorphin 1-7, all these peptide fragments are associated with PC1 or PC2 processing. Moreover, proteolysis of BDyn leads to the formation of Dyn A and Leu-Enk, two important opioid peptides. The rate of formation of both is significantly reduced in cellular fractions of spinal cord mutant mice. As a consequence, even partial inhibition of PC1 or PC2 may impair the endogenous opioid system.

Complications incurred because of delays in transferring patients to VA spinal cord injury treatment centers; report to the Congress [on the] Veterans Administration [and] Department of Defense by the Comptroller General of the United States.

"B-133044."

Diseases of the spinal cord and its membranes, and the various forms of paralysis arrising therefrom,- chorea and tetanus /

Mode of access: Internet.

Diseases of the spinal cord /

Mode of access: Internet.

Pathological conditions of the spinal cord in domestic animals, a review /

Caption title.

Pathological and practical researches on diseases of the brain and the spinal cord.

Mode of access: Internet.

Spinal cord injury : hope through research / [prepared by the Office of Scientific and Health Reports, National Institute of Neurological and Communicative Disorders and Stroke].

Mode of access: Internet.

Incidence of disability and characteristics of clients closed from plan with severe spinal cord injury, fiscal year 1972-73 /

"December 30, 1975."

Patterns of education and employment : rehabilitants from severe spinal cord injuries, fiscal year 1972-73 /

"June 1, 1974."

Professor Schroeder van der Kolk on the minute structure and functions of the spinal cord and medulla oblongata : and on the proximate cause and rational treatment of epilepsy /

Translation of two memoirs: Anatomisch physiologisch onderzoek over het fijnere zamenstel en de werking van het ruggemerg, published 1854, and Over het fijnere zamenstel en de werking van het verlangde ruggemerg en over de naaste oorzaak van epilepsie en hare rationele behandeling, published 1858.

Satisfaction with medical rehabilitation after spinal cord injury

Study Design. Retrospective Objective. To predict satisfaction with medical rehabilitation. Summary of Background Data. While spinal cord injury (SCI) patient satisfaction with life and community services has been investigated, satisfaction with medical rehabilitation has not. Methods. Information submitted to the Uniform Data System for Medical Rehabilitation ( 1998 - 2001) by 134 hospitals/rehabilitation facilities in the United States (n = 6,205 patients with SCI) was examined. Predictors were sociodemographic variables, Case Mix Groupings (CMG) ( 401 - 505, 5001), length of stay, rehospitalization, followup therapy, and health maintenance. Satisfaction was assessed at a mean of 92.2 days (SD 11.9 days) postdischarge. Data were analyzed according to who reported the outcome ( patient, n = 3,858 or family/other, n = 1,869). Statistical modeling was conducted using logistic regression. Results. High overall satisfaction was reported (94%). Significant predictors for the patient report data were CMG and rehospitalization. Compared with CMG 5001 ( short stay,

Integrating technology in the workplace for people with spinal cord injury

Computer technology can overcome mobility and functional limitations resulting from spinal cord injury (SCI) and enable re-employment. This study aimed to identify barriers and supports to effective technology use at work from the unique perspectives of technology users themselves. A qualitative research design was used to explore the perspectives of 11 technology users with SCI. In-depth, open-ended interviews and observations were conducted at each person’s workplace. Five major themes emerged: identifying the best or right technology; acquiring the technology; customizing and learning to use the technology; supporting the technology; and empowerment. Understanding these consumer perspectives enables professionals to empower people with SCI to optimize their work potential.

Patterns of neuronal activation in the rat brain and spinal cord in response to increasing durations of restraint stress

By most accounts the psychological stressor restraint produces a distinct pattern of neuronal activation in the brain. However, some evidence is incongruous with this pattern, leading us to propose that the restraint- induced pattern in the central nervous system might depend on the duration of restraint used. We therefore determined the pattern of neuronal activation ( as indicated by the presence of Fos protein) seen in the paraventricular nucleus (PVN), bed nucleus of the stria terminalis, amygdala, locus coeruleus, nucleus tractus solitarius (NTS), ventrolateral medulla (VLM) and thoracic spinal cord of the rat in response to 0, 15, 30 or 60 min periods of restraint. We found that although a number of cell groups displayed a linear increase in activity with increasing durations of restraint ( e. g. hypothalamic corticotrophin-releasing factor (CRF) cells, medial amygdala neurons and sympathetic preganglionic neurons of the thoracic spinal cord), a number of cell groups did not. For example, in the central amygdala restraint produced both a decrease in CRF cell activity and an increase in non-CRF cell activity. In the locus coeruleus, noradrenergic neurons did not display Fos in response to 15 min of restraint, but were significantly activated by 30 or 60 min restraint. After 30 or 60 min restraint a greater degree of activation of more rostral A1 noradrenergic neurons was observed compared with the pattern of A1 noradrenergic neurons in response to 15 min restraint. The results of this study demonstrate that restraint stress duration determines the amount and the pattern of neuronal activation seen in response to this psychological stressor.