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Biomedical subjects

L M Jordan

Publications and source records attributed to L M Jordan.

At least 19 recordsLinked to original sources
PubMed2005

Cholinergic and serotonergic excitation of ascending commissural neurons in the thoraco-lumbar spinal cord of the neonatal mouse.

Locomotion requires the coordination of the two sides of the spinal cord-a function fulfilled by commissural neurons. Ascending commissural neurons (aCNs) are known to be rhythmically active during locomotion, and mice lacking a population of aCNs display uncoupling between the left and right hemicords during locomotion. Acetylcholine (ACh) applied to the isolated spinal cord commonly produces left-right alternation, with co-contraction of ipsilateral flexor and extensor motoneuron groups. In this study, aCNs were examined in the neonatal mouse spinal cord after retrograde labeling with a fluorescent dextran. The axons of these cells crossed in the ventral commissure with many crossing in the same transverse plane as the cell body. For cells located in lamina VII and VIII, ACh (10-50 microM) depolarized 92% (13/14) of the cells tested. ACh depolarized and increased the excitability of aCNs in the presence of a decrease in input resistance. ACh was without significant effect on afterhyperpolarization amplitude or voltage threshold of action potential initiation. In those cells sensitive to application of ACh, 90% (9/10 cells) were also depolarized by 5HT (10-50 microM). Application of 5HT significantly increased the input resistance of these cells, and this effect was likely responsible for the observed increase in excitability, because significant effects on the afterhyperpolarization and voltage threshold were again not detected. The high proportion of aCNs excited by both ACh and 5HT suggests that direct activation of aCNs by these two neurotransmitters contributes to the production of a bilaterally coordinated locomotor-like rhythm in the isolated spinal cord.

Action Potentials↗
PubMed2005

Localization of spinal neurons activated during locomotion using the c-fos immunohistochemical method.

The c-fos immunohistochemical method of activity-dependent labeling was used to localize locomotor-activated neurons in the adult cat spinal cord. In decerebrate cats, treadmill locomotion was evoked by electrical stimulation of the mesencephalic locomotor region (MLR). Spontaneous or MLR-evoked fictive locomotion was produced in decerebrate animals paralyzed with a neuromuscular blocking agent. After bouts of locomotion during a 7- to 9-h time period, the animals were perfused and the L3-S1 spinal cord segments removed for immunohistochemistry. Control animals were subjected to the same surgical procedures but no locomotor task. Labeled cells were concentrated in Rexed's laminae III and IV of the dorsal horn and laminae VII, VIII, and X of the intermediate zone/ventral horn after treadmill locomotion. Cells in laminae VII, VIII, and X were labeled after fictive locomotion, but labeling in the dorsal horn was much reduced. In control animals, c-fos labeling was a small fraction of that observed in the locomotor animals. The results suggest that labeled cells in laminae VII, VIII, and X are premotor interneurons involved in the production of locomotion, whereas the laminae III and IV cells are those activated during locomotion due to afferent feedback from the moving limb. c-fos-labeled cells were most numerous in the L5-L7 segments, consistent with the distribution of locomotor activated neurons detected through the use of MLR-evoked field potentials.

Animals↗
PubMed2002

A population of oligodendrocytes derived from multipotent neural precursor cells expresses a cholinergic phenotype in culture and responds to ciliary neurotrophic factor.

Because oligodendrocytes and their precursors possess receptors for classical transmitters, and neurotransmitters such as glutamate and noradrenaline can mediate oligodendroglial proliferation and differentiation, it is possible that other neurotransmitters can also exert regulatory roles in oligodendrocyte function. We used mitogen-proliferated multipotent neuroepithelial precursors (neurospheres) and identified oligodendroglia that expressed markers traditionally found in cholinergic neurons. Regardless of culture conditions, there existed a large population of cells that resembled oligodendrocytes morphologically and coexpressed the oligodendrocyte-specific marker galactocerebroside (GalC) and the acetylcholine (ACh)-synthesizing enzyme choline acetyltransferase (ChAT). These cells did not express neuronal markers, and whole-cell recordings from cells with similar morphology displayed only outward currents in response to depolarizing voltage steps, further supporting their oligodendroglial identity. Another cholinergic marker, the vesicular ACh transporter, was also detected in GalC(+) oligodendrocytes. Furthermore, neurospheres cultured in the presence of the cholinergic receptor antagonist atropine showed a decrease in the number of GalC(+) spheres, implicating the muscarinic ACh receptor in oligodendrocyte development. The actions of neurotrophins and ciliary neurotrophic factor (CNTF) on these ChAT(+) oligodendrocytes were examined. Among these, CNTF treatment significantly increased oligodendrocytic process outgrowth. These results demonstrate classical cholinergic neuronal markers in oligodendrocytes as well as an effect of muscarinic receptor blockade on oligodendrocyte differentiation.

Acetylcholine↗
PubMed2001

State-dependent hyperpolarization of voltage threshold enhances motoneurone excitability during fictive locomotion in the cat.

Experiments were conducted on decerebrate adult cats to examine the effect of brainstem-evoked fictive locomotion on the threshold voltage (Vth) at which action potentials were initiated in hindlimb motoneurones. Measurements of the voltage threshold of the first spike evoked by intracellular injection of depolarizing ramp currents or square pulses were compared during control and fictive locomotor conditions. The sample of motoneurones included flexor and extensor motoneurones, and motoneurones with low and high rheobase currents. In all 38 motoneurones examined, action potentials were initiated at more hyperpolarized membrane potentials during fictive locomotion than in control conditions (mean hyperpolarization -8.0 +/- 5.5 mV; range -1.8 to -26.6 mV). Hyperpolarization of Vth occurred immediately at the onset of fictive locomotion and recovered in seconds (typically < 60 s) following the termination of locomotor activity. The Vth of spikes occurring spontaneously without intracellular current injection was also reduced during locomotion. Superimposition of rhythmic depolarizing current pulses on current ramps in the absence of locomotion did not lower Vth to the extent seen during fictive locomotion. We suggest that Vth hyperpolarization results from an as yet undetermined neuromodulatory process operating during locomotion and is not simply the result of the oscillations in membrane potential occurring during locomotion.The hyperpolarization of Vth for action potential initiation during locomotion is a state-dependent increase in motoneurone excitability. This Vth hyperpolarization may be a fundamental process in the generation of motoneurone activity during locomotion and perhaps other motor tasks.

Action Potentials↗
PubMed2001

Neurogenesis in postnatal mouse dorsal root ganglia.

Neurogenesis continues in various regions of the central nervous system (CNS) throughout life. As the mitogen basic fibroblast growth factor (bFGF) can proliferate neuronal precursors of CNS neurons in culture, and is also upregulated within adult dorsal root ganglia following axotomy, it is possible that the postnatal dorsal root ganglia contain bFGF-responsive neuronal precursors. We undertook cell culture of postnatal mouse dorsal root ganglia to demonstrate neurogenesis. Basic FGF induced a cellular proliferative response in dorsal root ganglia cell culture. After 2 weeks in serum-free medium containing bFGF, neurons were rarely observed. However, following removal of bFGF and addition of trophic factors, many cells were observed that morphologically resembled dorsal root ganglia neurons, stained for neuronal markers, and generated action potentials. Furthermore, bromodeoxyuridine, used as a marker of cytogenesis, was detected in neurofilament-160(+) and/or microtubule-associated protein-2(+) cells that morphologically resembled neurons. In addition to bFGF, epidermal growth factor, nerve growth factor, and sonic hedgehog were also capable of generating spherical cell clusters that contained cells that stained for neuronal markers following the addition of trophic factors. These results suggest that early postnatal dorsal root ganglia contain neural precursors that appear to proliferate in response to various factors and can then be induced to differentiate into neurons. In conclusion, the existence of neural precursors and the possibility of neurogenesis in postnatal dorsal root ganglia may provide a greater range of plasticity available to somatosensory systems during growth or following injury, perhaps to replace ineffectual or dying neurons.

Action Potentials↗
PubMed2001

Data-driven practice improvement: the AANA Foundation closed malpractice claims study.

Research in anesthesia risk management has focused primarily on adverse patient outcomes. Most risk management studies have evaluated the practices of the physician anesthesiologist, while minimal research has been conducted to examine anesthesia care provided by Certified Registered Nurse Anesthetists (CRNAs). For this reason, the American Association of Nurse Anesthetists Foundation supported an examination of closed malpractice claim files from St Paul Fire and Marine Insurance Company that involved insured CRNAs. A team of 8 CRNA researchers investigated 223 closed claim files that involved incidents from 1989 to 1997. The results indicated that preoperative physical status, patient age, surgical procedure, type of anesthetic, age of anesthesia provider, and the type of anesthesia providers, (e.g., CRNA alone vs CRNA and anesthesiologist working together) did not have a statistically significant relationship with adverse anesthetic outcomes. However, providing appropriate care, being vigilant, encountering a less severe adverse outcome, and not being able to prevent the outcome were associated with smaller monetary awards. The findings of this study support those of similar studies.

Adolescent↗
PubMed2000

The role of serotonin in reflex modulation and locomotor rhythm production in the mammalian spinal cord.

Over the past 40 years, much has been learned about the role of serotonin in spinal cord reflex modulation and locomotor pattern generation. This review presents an historical overview and current perspective of this literature. The primary focus is on the mammalian nervous system. However, where relevant, major insights provided by lower vertebrate models are presented. Recent studies suggest that serotonin-sensitive locomotor network components are distributed throughout the spinal cord and the supralumbar regions are of particular importance. In addition, different serotonin receptor subtypes appear to have different rostrocaudal distributions within the locomotor network. It is speculated that serotonin may influence pattern generation at the cellular level through modulation of plateau properties, an interplay with N-methyl-D-aspartate receptor actions, and afterhyperpolarization regulation. This review also summarizes the origin and maturation of bulbospinal serotonergic projections, serotonin receptor distribution in the spinal cord, the complex actions of serotonin on segmental neurons and reflex pathways, the potential role of serotonergic systems in promoting spinal cord maturation, and evidence suggesting serotonin may influence functional recovery after spinal cord injury.

Animals↗
PubMed2000

Dendritic L-type calcium currents in mouse spinal motoneurons: implications for bistability.

The intrinsic properties of mammalian spinal motoneurons provide them with the capability to produce high rates of sustained firing in response to transient inputs (bistability). Even though it has been suggested that a persistent dendritic calcium current is responsible for the depolarizing drive underlying this firing property, such a current has not been demonstrated in these cells. In this study, calcium currents are recorded from functionally mature mouse spinal motoneurons using somatic whole-cell patch-clamp techniques. Under these conditions a component of the current demonstrated kinetics consistent with a current originating at a site spatially segregated from the soma. In response to step commands this component was seen as a late-onset, low amplitude persistent current whilst in response to depolarizing-repolarizing ramp commands a low voltage clockwise current hysteresis was recorded. Simulations using a neuromorphic motoneuron model could reproduce these currents only if a noninactivating calcium conductance was placed in the dendritic compartments. Pharmacological studies demonstrated that both the late-onset and hysteretic currents demonstrated sensitivity to both dihydropyridines and the L-channel activator FPL-64176. Furthermore, the alpha1D subunits of L-type calcium channels were immunohistochemically demonstrated on motoneuronal dendrites. It is concluded that there are dendritically located L-type channels in mammalian motoneurons capable of mediating a persistent depolarizing drive to the soma and which probably mediate the bistable behaviour of these cells.

Animals↗
PubMed2000

A variable resolution x-ray detector for computed tomography: II. Imaging theory and performance.

A computed tomography (CT) imaging technique called variable resolution x-ray (VRX) detection provides variable image resolution ranging from that of clinical body scanning (1 cy/mm) to that of microscopy (100 cy/mm). In this paper, an experimental VRX CT scanner based on a rotating subject table and an angulated storage phosphor screen detector is described and tested. The measured projection resolution of the scanner is > or = 20 lp/mm. Using this scanner, 4.8-s CT scans are made of specimens of human extremities and of in vivo hamsters. In addition, the system's projected spatial resolution is calculated to exceed 100 cy/mm for a future on-line CT scanner incorporating smaller focal spots (0.1 mm) than those currently used and a 1008-channel VRX detector with 0.6-mm cell spacing.

Algorithms↗
PubMed2000

Spinal cholinergic neurons activated during locomotion: localization and electrophysiological characterization.

The objective of the present study was to determine the location of the cholinergic neurons activated in the spinal cord of decerebrate cats during fictive locomotion. Locomotion was induced by stimulation of the mesencephalic locomotor region (MLR). After bouts of locomotion during a 7-9 h period, the animals were perfused and the L(3)-S(1) spinal cord segments removed. Cats in the control group were subjected to the same surgical procedures but no locomotor task. The tissues were sectioned and then stained by immunohistochemical methods for detection of the c-fos protein and choline acetyltransferase (ChAT) enzyme. The resultant c-fos labeling in the lumbar spinal cord was similar to that induced by fictive locomotion in the cat. ChAT-positive cells also clearly exhibited fictive locomotion induced c-fos labeling. Double labeling with c-fos and ChAT was observed in cells within ventral lamina VII, VIII, and possibly IX. Most of them were concentrated in the medial portion of lamina VII close to lamina X, similar in location to the partition and central canal cells found by Barber and collaborators. The number of ChAT and c-fos-labeled neurons was increased following fictive locomotion and was greatest in the intermediate gray, compared with dorsal and ventral regions. The results are consistent with the suggestion that cholinergic interneurons in the lumbar spinal cord are involved in the production of fictive locomotion. Cells in the regions positive for double-labeled cells were targeted for electrophysiological study during locomotion, intracellular filling, and subsequent processing for ChAT immunohistochemistry. Three cells identified in this way were vigorously active during locomotion in phase with ipsilateral extension, and they projected to the contralateral side of the spinal cord. Thus a new population of spinal cord cells can be defined: cholinergic partition cells with commissural projections that are active during the extension phase of locomotion.

Animals↗
PubMed2000

Critical decisions in the management of endoscopic perforations of the colon.

The ideal management of suspected colon perforation following colonoscopy remains elusive because the incidence is only 0.1 to 2.0 per cent. The patient with obvious perforation deserves immediate exploration, but the patient with equivocal findings poses a diagnostic dilemma. We propose an algorithm based on the results of water-soluble contrast enema that allows for rapid, definitive surgical decision-making. If perforation is confirmed, early operation allows for primary repair without resection or colostomy, or if no perforation is identified, medical management can be undertaken with confidence. This algorithm should ensure that the surgical management of this potentially lethal complication is not unnecessarily delayed.

Aged↗
PubMed1998

Initiation of locomotion in mammals.

Several "locomotor regions" of the mammalian brain stem can be stimulated, either electrically or chemically, to induce locomotion. Active cells labeled with c-fos within the mesencephalic locomotor region (MLR) have been found in the periaqueductal gray, the cuneiform nucleus, the pedunculopontine nucleus, and the locus coeruleus. Different subsets of these nuclei appear to be activated during locomotion produced in different behavioral contexts. The locomotor nuclei can be classified into areas associated with exploratory, appetitive, and defensive locomotion, in accordance with the proposal of Sinnamon (1993, Prog. Neurobiol. 41: 323-344). The interpretation of lesion studies designed to reveal areas of the brain essential for locomotion must be based on knowledge of the nuclei which become active in the specific locomotor task being tested. An argument is put forward in favor of the continued use of the term "mesencephalic locomotor region."

Animals↗
PubMed1995

Conformational study of biotinylated DNA oligonucleotides utilizing two-dimensional nuclear magnetic resonance and molecular dynamics.

The solution structure of DNA oligonucleotides containing a biotin group covalently attached through a linker arm to the 5' end has been studied by two-dimensional NMR and molecular modeling, in an attempt to determine whether the biotin end group is accessible to avidin binding. Such experiments are useful in suggesting that purification of synthetic DNA oligonucleotides by avidin-biotin affinity chromatography is carried out with a minimum amount of intramolecular association of biotin with potential binding sites within the DNA. Two DNA oligonucleotides that form hairpin structures have been proposed as possible worst case scenarios where biotin would not be available for avidin binding. These structures are d(XGCGCGTTTTCGCGC) and d(XGCGCGTTTTCGCGCAAAAA), where X represents the biotin and linker structures. No NOEs were detected between the biotin/linker portion of the molecule and the DNA hairpin. In addition, the magnitude of the NOEs between neighboring groups in the biotin/linker was approximately an order of magnitude smaller than that of the neighbors at a comparable distance within the DNA hairpin, suggesting that the biotin/linker undergoes considerable additional motion compared to the DNA hairpin. Molecular dynamics calculations also show that the biotin/linker undergoes a considerable range of motion. Thus, all data indicate that the biotin is not immediately associated with the hairpin and should be available for binding to avidin under chromatographically relevant solvent conditions.

Base Sequence↗
PubMed1995

C-terminals on motoneurons: electron microscope localization of cholinergic markers in adult rats and antibody-induced depletion in neonates.

C-terminals on motoneurons are defined as those accompanied by characteristic postsynaptic specializations termed subsurface cisterns. We have previously shown, by light microscope immunolabelling methods, that subsurface cisterns occur regularly beneath choline acetyltransferase- and acetylcholinesterase-containing boutons on motoneurons. In the present study, the cholinergic nature of C-terminals suggested by these results was further investigated by immunohistochemistry and electron microscopy in adult rats and in neonates treated with a murine monoclonal acetylcholinesterase antibody which was previously shown to cause immunological lesions of central cholinergic systems. In both the facial nucleus and lumbar segment of spinal cord of adult rats, C-terminals were seen intensely immunostained for the cholinergic markers choline acetyltransferase and acetylcholinesterase. Immunolabelled terminals made contact with either neuronal somata or large calibre dendrites, which were positive for the cholinergic markers, and exhibited club-shaped or thin elongated morphologies suggestive of terminal or en passant type synaptic interactions. The close relationship found between cholinergic markers and immunolabelled subsurface cisterns in adults was maintained on motoneurons of eight-day-old rats. While subcutaneous treatment of newborn rat with acetylcholinesterase antibody appeared to have no effect on the distribution of immunopositive subsurface cisterns in motoneurons when examined on postnatal day 8, the density of labelling for the two cholinergic markers around these neurons was reduced. Areas of neuropil immediately surrounding motoneurons in treated animals often showed signs of extensive swelling and deterioration indicative of a lesion event, and these motoneurons frequently displayed subsurface cisterns unapposed to C-terminals. These results support our earlier conclusion, based on light microscope investigation, that the majority if not all C-terminals are cholinergic in the areas investigated and demonstrate the potential utility of immunolesion methods in the study of C-terminal function.

Animals↗