SEARCH · Search PubMed

Results for “Generations”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources

PubMed2006

Influence of marital history over two and three generations on early death. A longitudinal study of Danish men born in 1953.

BACKGROUND: This study examined the effects of marital status over two and three generations on last generation's mortality, and tested the hypothesis of an effect of the latest status (proximity effect) as well as the hypothesis of an accumulative effect. METHODS: The study population covers a random sample of all boys born in the the metropolitan area of Copenhagen with complete data from interviews and registers on two and three generation's marital status, socioeconomic position variables, and last generation's admission to psychiatric hospital, n = 2614. Among these 105 deaths occurred. Cox proportional hazards regression models were used to estimate the effect of marital status on mortality. RESULTS: Never married sons showed a considerably increased mortality compared with their married counterparts in the adjusted analyses. Mother's marital status at childbirth was also associated with increased mortality among the sons. There was no independent effect of maternal grandparent's experience of divorce on third generation's mortality. Son's marital status was the strongest marital status predictor of mortality. Accumulation of both two and three generations' marital status was significantly associated with mortality risk in a dose-response pattern. All analyses were adjusted for socioeconomic position variables and mental health. CONCLUSIONS: These results support the proximity hypothesis as son's marital status was the strongest predictor of mortality, and suggest an accumulative effect as each of the three non-married generations added to an increased mortality risk.

Adolescent↗

PubMed2000

Generation of complement C3 and expression of cell membrane complement inhibitory proteins by human bronchial epithelium cell line.

BACKGROUND: The interrelationship between human airway epithelium and complement proteins may affect airway defence, airway function, and airway epithelial integrity. A study was undertaken to determine (1) whether unstimulated human bronchial epithelium generates complement proteins and expresses cell membrane complement inhibitory proteins (CIP) and (2) whether stimulation by proinflammatory cytokines affects the generation of complement and expression of cell membrane CIP by these cells. METHODS: Human bronchial epithelium cell line BEAS-2B was cultured in a serum-free medium. Cells were incubated with and without proinflammatory cytokines to assess unstimulated and stimulated generation of complement C3, C1q and C5 (by ELISA), and to examine the expression of cell membrane CIP decay accelerating factor (DAF; CD55), membrane cofactor protein (MCP; CD46), and CD59 (protectin) by flow cytometry analysis. RESULTS: Unstimulated human bronchial epithelial cell line BEAS-2B in serum-free medium generates complement C3 (mean 32 ng/10(6) cells/72 h, range 18-52) but not C1q and C5, and expresses cell membrane DAF, MCP, and CD59. Interleukin (IL)-1alpha (100 U/ml/72 h) and tumour necrosis factor (TNF-alpha; 1000 U/ml/72 h) increased generation of C3 up to a mean of 78% and 138%, respectively, above C3 generation by unstimulated cells. DAF was the only cell membrane CIP affected by cytokine stimulation. Interferon (IFN)-gamma (10 U/ml/72 h) and TNF-alpha (1000 U/ml/72 h) increased DAF expression up to a mean of 116% and 45%, respectively, above that in unstimulated cells. MCP and CD59 expression was not consistently affected by IL-1alpha, TNF-alpha, or IFN-gamma. CONCLUSIONS: Local generation of complement C3 and expression of cell membrane CIP by human bronchial epithelium and its modulation by proinflammatory cytokines might be an additional regulatory mechanism of local airway defence and may affect airway function and epithelial integrity in health and disease.

Bronchi↗

PubMed1995

Reduction in leukotriene B4 generation by bronchoalveolar lavage cells in asthma.

BACKGROUND: Leukotrienes are inflammatory mediators implicated in the pathogenesis of asthma. The capacity of inflammatory cells within the airways to generate leukotrienes may be altered in asthma. This hypothesis was tested using bronchoalveolar lavage (BAL) to sample cells within the airways from atopic asthmatic and normal subjects, and by measuring their capacity to generate leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in response to A23187, a potent stimulus of leukotriene generation. METHODS: Bronchoalveolar lavage was performed in 12 mild asymptomatic atopic asthmatic patients and 12 normal subjects. Mixed BAL cell aliquots (approximately 80% alveolar macrophages) were incubated with 0-20 microM A23187 for 10 minutes and with 4 microM A23187 for 0-30 minutes, and leukotrienes were measured by radioimmunoassay and high performance liquid chromatography. RESULTS: Mixed BAL cells from asthmatic subjects generated less LTB4 than cells from normal subjects in dose response and time course experiments (area under the curve 81.5 (0.0-228.5) ng.min.10(-6) cells in asthmatic subjects and 197.9 (13.9-935.6) ng.min.10(-6) cells in normal subjects. There were no differences in LTC4 generation between BAL cells from asthmatic and normal subjects. CONCLUSIONS: Generation of LTB4 by BAL cells from atopic asthmatic subjects in response to A23187 was reduced. As the alveolar macrophage is the major source of LTB4 in BAL cells, these results probably reflect reduced generation of LTB4 by alveolar macrophages from asthmatic patients. This may be a consequence of monocyte migration into the lung, or altered alveolar macrophage function in asthma, or both.

Adult↗

PubMed1997

Involvement of an NAD(P)H oxidase-like enzyme in superoxide anion and hydrogen peroxide generation by rat type II cells.

BACKGROUND: Although alveolar macrophages are considered to be the primary cellular mediators of host defence in the lung, there is increasing evidence that type II cells may also play an active role in host defence. A study was undertaken to investigate whether type II cells generate O2-. and H2O2 via an NADPH oxidase-like system and whether exposure of the type II cells to soluble or particulate stimuli known to activate NADPH oxidase in macrophages also leads to increased production of H2O2. METHODS: Rat type II cells and alveolar macrophages were exposed to 10, 100, or 1000 nM phorbol-12-myristate-13-acetate (PMA) and the production of O2-. and H2O2 was determined by chemiluminescence. Thirty minutes before stimulation with 1 microM PMA type II cells were also exposed to the same concentrations of a protein kinase C (PKC) antagonist GF109203x, the non-selective protein kinase inhibitor staurosporine (1, 10, or 100 nM), or the NADPH oxidase inhibitor diphenyliodonium chloride (DPI) (1, 10, 100, or 1000 microM). The effects of arachidonic acid, zymosan and Staphylococcus aureus on H2O2 production were determined. Cell membrane fractions from type II cells and macrophages were assayed for NADPH oxidase activity. RESULTS: After exposure to 1 microM PMA, O2-. and H2O2 generation increased 6.3-fold and 9.0-fold, respectively, in type II cells and 2.4-fold and 5.2-fold, respectively, in macrophages. In contrast to the macrophages, the increase in O2-. and H2O2 generation by type II cells was completely prevented by 1 mM KCN. Preexposure to GF109203x, staurosporine, or DPI completely prevented the rise in O2-. and H2O2 generation. Mean (SD) NADPH oxidase activity of 138 (38) nmol O2-./min/mg protein was found in membrane fraction I of the type II cells, and 102 (31) nmol O2-./min/mg protein in fraction II. Macrophages showed higher NADPH oxidase activity in membrane fraction II. In type II cells exposure to arachidonic acid led to a significant 5.3-fold increase in H2O2 generation, exposure to zymosan increased H2O2 generation 46-fold, and exposure to S aureus 25-fold with a maximum 30-50 minutes after addition of the bacteria. CONCLUSIONS: Type II cells generate O2-. and H2O2 via a PKC-mediated activation of an NAD(P)H oxidase-like membrane bound enzyme. Arachidonic acid, zymosan, and bacteria also give rise to increased H2O2 production. Type II cells might thus play an active role in host defence.

Animals↗

PubMedDate not supplied

The AAPM/RSNA physics tutorial for residents. X-ray generators.

The x-ray generator delivers the electrical power to energize the x-ray tube and permits the selection of x-ray energy, x-ray quantity, and exposure time. Major internal components of the generator include transformers, diodes and rectifier circuits, filament and stator circuits, timer switches, and kilovolt and milliampere meters. Single-phase, three-phase, high-frequency, and constant potential generators produce different voltage waveforms (ripple) and x-ray beam spectra. Phototimer and automatic brightness control subsystems measure radiation exposure incident on the image receptor to give instantaneous feedback for optimal radiographic film densities and fluoroscopic image brightness, respectively. At the generator control console, the operator sets the tube voltage, tube current, exposure time, phototimer film density, spot film acquisition, and fluoroscopic parameters. Selection of generator power and options depends on the intended clinical use. X-ray tube focal spot size and power loading capability should be matched to the x-ray generator and clinical imaging requirements. Single and multiple exposure rating charts as well as anode and housing thermal characteristic charts indicate power input and dissipation rates specific to a generator and x-ray tube target and housing.

Humans↗

PubMed2006

Intracellular cAMP: the "switch" that triggers on "spontaneous transient outward currents" generation in freshly isolated myocytes from thoracic aorta.

Spontaneous transient outward currents (STOCs) have been reported in resistance and small arteries but have not yet been found in thoracic aorta. Do thoracic aorta myocytes possess cellular machinery that generates STOCs? It was found that the majority of aortic myocytes do not generate STOCs. STOCs were generated in 8.7% of freshly isolated aortic myocytes. Myocytes that did not generate STOCs we have called "silent" myocytes and myocytes with STOCs have been called "active." STOCs recorded in active myocytes were voltage dependent and were inhibited by ryanodine, caffeine, and charybdotoxin. Forskolin was reported to increase STOCs frequency in myocytes isolated from resistance arteries. Forskolin (10 microM) triggered STOCs generation in 35.1% of silent aortic myocytes. In 36.8% percent of silent myocytes, forskolin did not trigger STOCs but increased the amplitude of charybdotoxin-sensitive outward net current to 136.1 +/- 8.5% at 0 mV. Membrane-permeable 8BrcAMP triggered STOCs generation in 38.7% of silent myocytes. Forskolin- or 8BrcAMP-triggered STOCs were inhibited by charybdotoxin. 8BrcAMP also increased open probability of BK(Ca) channels in BAPTA-AM-pretreated cells. Our data demonstrate that, in contrast to resistance arteries, STOCs are present just in the minority of myocytes in the thoracic aorta. However, cellular machinery that generates STOCs can be "switched" on by cAMP. Such an inactive cellular mechanism could modulate the contractility of the thoracic aorta in response to physiological demand.

Animals↗

PubMed1994

Measurement and characterization of free radical generation in reoxygenated human endothelial cells.

The endothelial cell is thought to be an important site of free radical generation in ischemic tissues. It has been demonstrated that endothelial cells from several species generate a burst of free radical generation upon reoxygenation; however, it has been suggested that human endothelial cells are not similarly capable of generating free radicals on reoxygenation. In view of the central importance of revascularization with accompanying reoxygenation in the clinical treatment of tissue ischemia/infarction, we have performed studies to determine the presence, mechanism, and kinetics of free radical generation in human endothelial cells. Therefore, we subjected cultured human umbilical vein endothelial cells to anoxia followed by reoxygenation. Cell suspensions of 10(7) cells/ml were subjected to varying periods of anoxia and reoxygenation. On reoxygenation with addition of a 50 mM concentration of the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), after 90 min of anoxia an electron paramagnetic resonance (EPR) signal was observed consisting of 2 components: a quartet 1:2:2:1 DMPO-OH signal, aN = aH = 14.9 G, and a six-peaked DMPO-R signal, aN = 15.6 G aH = 22.9 G, whereas cells in air gave no signal. The observed signal was quenched by superoxide dismutase (SOD) or catalase. Deferoxamine decreased the measured radical signals by 40%. Cyclooxygenase blockers did not decrease radical generation, but the xanthine oxidase blocker oxypurinol did decrease radical generation by 60%.

Animals↗

PubMed2000

Stimulation by iodide of H(2)O(2) generation in thyroid slices from several species.

The regulation of thyroid metabolism by iodide involves numerous inhibitory effects. However, in unstimulated dog thyroid slices, a small inconstant stimulatory effect of iodide on H(2)O(2) generation is observed. The only other stimulatory effect reported with iodide is on [1-(14)C]glucose oxidation, i.e., on the pentose phosphate pathway. Because we have recently demonstrated that the pentose phosphate pathway is controlled by H(2)O(2) generation, we study here the effect of iodide on basal H(2)O(2) generation in thyroid slices from several species. Our data show that in sheep, pig, bovine, and to a lesser extent dog thyroid, iodide had a stimulatory effect on H(2)O(2) generation. In horse and human thyroid, an inconstant effect was observed. We demonstrate in dogs that the stimulatory effect of iodide is greater in thyroids deprived of iodide, raising the possibility that differences in thyroid iodide pool may account, at least in part, for the differences between the different species studied. This represents the first demonstration of an activation by iodide of a specialized thyroid function. In comparison with conditions in which an inhibitory effect of iodide on H(2)O(2) generation is observed, the stimulating effect was observed for lower concentrations and for a shorter incubation time with iodide. Such a dual control of H(2)O(2) generation by iodide has the physiological interest of promoting an efficient oxidation of iodide when the substrate is provided to a deficient gland and of avoiding excessive oxidation of iodide and thus synthesis of thyroid hormones when it is in excess. The activation of H(2)O(2) generation may also explain the well described toxic effect of acute administration of iodide on iodine-depleted thyroids.

Animals↗

PubMed2003

Bradykinin induces mitochondrial ROS generation via NO, cGMP, PKG, and mitoKATP channel opening and leads to cardioprotection.

Bradykinin (BK) mimics ischemic preconditioning by generating reactive oxygen species (ROS). To identify intermediate steps that lead to ROS generation, rabbit cardiomyocytes were incubated in reduced MitoTracker Red stain, which becomes fluorescent after exposure to ROS. Fluorescence intensity in treated cells was expressed as a percentage of that in paired, untreated cells. BK (500 nM) caused a 51 +/- 16% increase in ROS generation (P < 0.001). Coincubation with either the BK B2-receptor blocker HOE-140 (5 microM) or the free radical scavenger N-(2-mercaptopropionyl)glycine (1 mM) prevented this increase, which confirms that the response was receptor mediated and ROS were actually being measured. Closing mitochondrial ATP-sensitive K+ (mitoKATP) channels with 5-hydroxydecanoate (5-HD, 1 mM) prevented increased ROS generation. BK-induced ROS generation was blocked by Nomega-nitro-m-arginine methyl ester (m-NAME, 200 microM), which implicates nitric oxide as an intermediate. Blockade of guanylyl cyclase with 1-H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10 microM) aborted BK-induced ROS generation but not that from diazoxide, a direct opener of mitoKATP channels. The protein kinase G (PKG) blocker 8-bromoguanosine-3',5'-cyclic monophosphorothioate (25 microM) eliminated the effects of BK. Conversely, direct activation of PKG with 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (100 microM) increased ROS generation (39 +/- 15%; P < 0.004) similar to BK. This increase was blocked by 5-HD. Finally, the nitric oxide donor S-nitroso-N-acetylpenicillamine (1 microM) increased ROS by 34 +/- 6%. This increase was also blocked by 5-HD. In intact rabbit hearts, BK (400 nM) decreased infarction from 30.5 +/- 3.0 of the risk zone in control hearts to 11.9 +/- 1.4% (P < 0.01). This protection was aborted by either 200 microM m-NAME or 2 microM ODQ (35.4 +/- 5.7 and 30.4 +/- 3.0% infarction, respectively; P = not significant vs. control). Hence, BK preconditions through receptor-mediated production of nitric oxide, which activates guanylyl cyclase. The resulting cGMP activates PKG, which opens mitoKATP. Subsequent release of ROS triggers cardioprotection.

Adenosine Triphosphate↗

PubMed2004

Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology.

The endothelial generation of reactive oxygen species (ROS) is important both physiologically and in the pathogenesis of many cardiovascular disorders. ROS generated by endothelial cells include superoxide (O2-*), hydrogen peroxide (H2O2), peroxynitrite (ONOO-*), nitric oxide (NO), and hydroxyl (*OH) radicals. The O2-* radical, the focus of the current review, may have several effects either directly or through the generation of other radicals, e.g., H2O2 and ONOO-*. These effects include 1) rapid inactivation of the potent signaling molecule and endothelium-derived relaxing factor NO, leading to endothelial dysfunction; 2) the mediation of signal transduction leading to altered gene transcription and protein and enzyme activities ("redox signaling"); and 3) oxidative damage. Multiple enzymes can generate O2-*, notably xanthine oxidase, uncoupled NO synthase, and mitochondria. Recent studies indicate that a major source of endothelial O2-* involved in redox signaling is a multicomponent phagocyte-type NADPH oxidase that is subject to specific regulation by stimuli such as oscillatory shear stress, hypoxia, angiotensin II, growth factors, cytokines, and hyperlipidemia. Depending on the level of oxidants generated and the relative balance between pro- and antioxidant pathways, ROS may be involved in cell growth, hypertrophy, apoptosis, endothelial activation, and adhesivity, for example, in diabetes, hypertension, atherosclerosis, heart failure, and ischemia-reperfusion. This article reviews our current knowledge regarding the sources of endothelial ROS generation, their regulation, their involvement in redox signaling, and the relevance of enhanced ROS generation and redox signaling to the pathophysiology of cardiovascular disorders where endothelial activation and dysfunction are implicated.

Animals↗

PubMed1985

Model of a pattern generator for locomotion in mammals.

This paper presents an analytic model of a limb pattern generator that can produce complex muscle activation patterns such as those shown to control the limbs of cats. The limb pattern generator is considered to have a tonic input and six outputs; this provides for flexion and extension of representative muscles for each of the three joints of the limb. The pattern generator functions as a community of labile synthesized relaxation oscillators that alters its output in response to input. This model was studied using electromyographic data from an experiment conducted on an acute postmammillary cat preparation. The results suggest that the limb pattern generator can be represented as three subsystems: an oscillator that produces the fundamental frequency of the output in response to the tonic signal, nonlinear shaping functions that mold the oscillator output into the basic complex pattern, and appropriate weighting functions that generate the muscle activity pattern from basic waveforms. The model can account for speed changes in locomotion with a relatively smooth change of system parameters. The pattern generator model is generative, amenable to simulation studies, and can be realized by a neural network.

Animals↗

PubMed2005

Diaphragmatic free radical generation increases in an animal model of heart failure.

Heart failure evokes diaphragm weakness, but the mechanism(s) by which this occurs are not known. We postulated that heart failure increases diaphragm free radical generation and that free radicals trigger diaphragm dysfunction in this condition. The purpose of the present study was to test this hypothesis. Experiments were performed using halothane-anesthetized sham-operated control rats and rats in which myocardial infarction was induced by ligation of the left anterior descending coronary artery. Animals were killed 6 wk after surgery, the diaphragms were removed, and the following were assessed: 1) mitochondrial hydrogen peroxide (H2O2) generation, 2) free radical generation in resting and contracting intact diaphragm using a fluorescent-indicator technique, 3) 8-isoprostane and protein carbonyls (indexes of free radical-induced lipid and protein oxidation), and 4) the diaphragm force-frequency relationship. In additional experiments, a group of coronary ligation animals were treated with polyethylene glycol-superoxide dismutase (PEG-SOD, 2,000 units x kg(-1) x day(-1)) for 4 wk. We found that coronary ligation evoked an increase in free radical formation by the intact diaphragm, increased diaphragm mitochondrial H2O2 generation, increased diaphragm protein carbonyl levels, and increased diaphragm 8-isoprostane levels compared with controls (P < 0.001 for the first 3 comparisons, P < 0.05 for 8-isoprostane levels). Force generated in response to 20-Hz stimulation was reduced by coronary ligation (P < 0.05); PEG-SOD administration restored force to control levels (P < 0.03). These findings indicate that cardiac dysfunction due to coronary ligation increases diaphragm free radical generation and that free radicals evoke reductions in diaphragm force generation.

Animals↗

PubMed1982

Mechanisms underlying pattern generation in lobster stomatogastric ganglion as determined by selective inactivation of identified neurons. II. Oscillatory properties of pyloric neurons.

1. The motor program controlling the rhythmic movements of the pyloric region of the lobster stomach is generated by neurons in the stomatogastric ganglion. Neurons within this "pyloric network" were tested for their ability to generate bursting pacemaker potentials (BPPs). For these experiments, each neuron to be tested was isolated from other cells within the stomatogastric ganglion by use of the dye-sensitized photoinactivation technique. All extraganglionic inputs to the stomatogastric ganglion were blocked. 2. Only one cell in the pyloric network, the anterior burster (AB) cell, continued to generate BPPs when isolated in this manner. The AB cell is also the only interganglionic interneuron in the pyloric network. 3. Two other neurons that were previously thought to be endogenous bursters, the pyloric dilator (PD) cells, fired tonically when isolated from synaptic input. However, tonic stimulation of the stomatogastric nerve elicited BPP generation in the PD cells. These membrane-potential oscillations were generated for periods of up to a minute following cessation of the stimulus. 4. Stimulation of the stomatogastric nerve also elicited BPP generation in two other pyloric cell types: the ventricular dilator (VD) and lateral pyloric (LP) cells. 5. A reduced subset of the pyloric network was obtained by photoinactivation of several cells, including the spontaneously oscillatory AB interneuron. When inputs to this reduced network were blocked, all pattern generation ceased. A short stimulus to the stomatogastric nerve induced an episode of coordinated patterned activity from these cells. Thus, BPP production contributes to the production and stability of the pyloric motor program.

Animals↗

PubMed1984

Model of electroretinogram b-wave generation: a test of the K+ hypothesis.

Generation of the electroretinogram b-wave is simulated with a computer model representing a dark-adapted amphibian retina. The simulation tests the K+ hypothesis of b-wave generation, which holds that b-wave currents arise from localized Müller cell depolarizations generated by light-evoked increases in extracellular K+ concentration, [K+]o. The model incorporates the following components and processes quantitatively: 1) two time-dependent K+ sources representing the light-evoked [K+]o increases in the inner and outer plexiform layers, 2) a time- and [K+]o-dependent K+ sink representing the [K+]o decrease in the rod inner segment layer, 3) diffusion of released K+ through extracellular space, 4) active K+ reuptake and passive K+ drift across the Müller cell membrane, 5) spatial variations in the tortuosity factor and the volume fraction of extracellular space, 6) an extraretinal shunt resistance. Müller cells are modeled with 1) cytoplasmic resistance, 2) spatial variations in membrane permeability to K+, and 3) a membrane potential specified by the Nernst equation and transmembrane current flow. For specified K+ source and sink densities, the model computes [K+]o variations in time and retinal depth. Based on these [K+]o distributions, Müller cell potentials, current source-density profiles, and intraretinal and transretinal voltages are calculated. Imposed [K+]o distributions similar to those seen experimentally during the b-wave lead to the generation of a transient b-wave response and to a prolonged Müller response in the model system. These response time courses arise because the b-wave is dominated by the short-lived distal [K+]o increase, while the Müller response primarily reflects the long-lived proximal [K+]o increase. Current source-density distributions and intraretinal voltage profiles that are generated by the model at the peak of the b-wave closely resemble experimental results. The model generates a realistic slow PIII potential in response to prolonged [K+]o decreases in the distal retina and reproduces the K+ ejection results of Yanagida and Tomita (50) accurately. Simulations also suggest that tissue damage caused by K+-selective micropipettes in experimental preparations can lead to an underestimation of the distal [K+]o increase. The simulations demonstrate that the spatiotemporal properties of intraretinal b-wave voltages and currents and Müller cell responses can be generated according to the K+ hypothesis: by passive Müller cell depolarization driven by variations in [K+]o.

Animals↗

PubMed1989

Human cortical potentials evoked by stimulation of the median nerve. I. Cytoarchitectonic areas generating short-latency activity.

1. The anatomic generators of human median nerve somatosensory evoked potentials (SEPs) in the 40 to 250-ms latency range were investigated in 54 patients by means of cortical-surface and transcortical recordings obtained during neurosurgery. 2. Contralateral stimulation evoked three groups of SEPs recorded from the hand representation area of sensorimotor cortex: P45-N80-P180, recorded anterior to the central sulcus (CS) and maximal on the precentral gyrus; N45-P80-N180, recorded posterior to the CS and maximal on the postcentral gyrus; and P50-N90-P190, recorded near and on either side of the CS. 3. P45-N80-P180 inverted in polarity to N45-P80-N180 across the CS but was similar in polarity from the cortical surface and white matter in transcortical recordings. These spatial distributions were similar to those of the short-latency P20-N30 and N20-P30 potentials described in the preceding paper, suggesting that these long-latency potentials are generated in area 3b of somatosensory cortex. 4. P50-N90-P190 was largest over the anterior one-half of somatosensory cortex and did not show polarity inversion across the CS. This spatial distribution was similar to that of the short-latency P25-N35 potentials described in the preceding paper and, together with our and Goldring et al. 1970; Stohr and Goldring 1969 transcortical recordings, suggest that these long-latency potentials are generated in area 1 of somatosensory cortex. 5. SEPs of apparently local origin were recorded from several regions of sensorimotor cortex to stimulation of the ipsilateral median nerve. Surface and transcortical recordings suggest that the ipsilateral potentials are generated not in area 3b, but rather in other regions of sensorimotor cortex perhaps including areas 4, 1, 2, and 7. This spatial distribution suggests that the ipsilateral potentials are generated by transcallosal input from the contralateral hemisphere. 6. Recordings from the periSylvian region were characterized by P100 and N100, recorded above and below the Sylvian sulcus (SS) respectively. This distribution suggests a tangential generator located in the upper wall of the SS in the second somatosensory area (SII). In addition, N125 and P200, recorded near and on either side of the SS, suggest a radial generator in a portion of SII located in surface cortex above the SS. 7. In comparison with the short-latency SEPs described in the preceding paper, the long-latency potentials were more variable and were more affected by intraoperative conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain↗

PubMed1989

Human cortical potentials evoked by stimulation of the median nerve. II. Cytoarchitectonic areas generating long-latency activity.

Cerebral Cortex↗

PubMed2001

Pattern generation for walking and searching movements of a stick insect leg. I. Coordination of motor activity.

During walking, the six legs of a stick insect can be coordinated in different temporal sequences or gaits. Leg coordination in each gait is controlled and stabilized by coordinating mechanisms that affect the action of the segmental neuronal networks for walking pattern generation. At present, the motor program for single walking legs in the absence of movement-related coordinating intersegmental influences from the other legs is not known. This knowledge is a prerequisite for the investigation of the segmental neuronal mechanisms that control the movements of a leg and to study the effects of intersegmental coordinating input. A stick insect single middle leg walking preparation has been established that is able to actively perform walking movements on a treadband. The walking pattern showed a clear division into stance and swing phases and, in the absence of ground contact, the leg performed searching movements. We describe the activity patterns of the leg muscles and motoneurons supplying the coxa-trochanteral joint, the femur-tibial joint, and the tarsal leg joints of the middle leg during both walking and searching movements. Furthermore we describe the temporal coordination between them. During walking movements, the coupling between the leg joints was phase-constant; in contrast during searching movements, the coupling between the leg joints was dependent on cycle period. The motor pattern of the single leg generated during walking exhibits similarities with the motor pattern generated during a tripod gait in an intact animal. The generation of walking movements also drives the activity of thoraco-coxal motoneurons of the deafferented and de-efferented thoraco-coxal leg joint in a phase-locked manner, with protractor motoneurons being active during swing and retractor motoneurons being active during stance. These results show that for the single middle leg, a basic walking motor pattern is generated sharing similarities with the tripod gait and that the influence of the motor pattern generated in the distal leg joints is sufficient for driving the activity of coxal motoneurons so an overall motor pattern resembling forward walking is generated.

Animals↗

PubMed2002

Spontaneous miniature hyperpolarizations affect threshold for action potential generation in mudpuppy cardiac neurons.

Mudpuppy parasympathetic neurons exhibit spontaneous miniature hyperpolarizations (SMHs) that are generated by potassium currents, which are spontaneous miniature outward currents (SMOCs), flowing through clusters of large conductance voltage- and calcium (Ca(2+))-activated potassium (BK) channels. The underlying SMOCs are initiated by a Ca(2+)-induced Ca(2+) release (CICR) mechanism. Perforated-patch whole cell voltage recordings were used to determine whether activation of SMHs contributed to action potential (AP) repolarization or affected the latency to AP generation. Blockade of BK channels by iberiotoxin (IBX, 100 nM) slowed AP repolarization and increased AP duration. Treatment with omega-conotoxin GVIA (3 microM) or nifedipine (10 microM) to inhibit Ca(2+) influx through N- or L-type voltage-dependent calcium channels (VDCCs), respectively, also decreased the rate of AP repolarization and increased AP duration. Elimination of CICR by treatment with either thapsigargin (1 microM) or ryanodine (10 microM) produced no significant change in AP repolarization or duration. Blockade of BK channels with IBX and inhibition of N-type VDCCs with omega-conotoxin GVIA, but not inhibition of L-type VDCCs with nifedipine, decreased the latency of AP generation. A decrease in latency to AP generation occurred with elimination of SMHs by inhibition of CICR following treatment with thapsigargin. Ryanodine treatment decreased AP latency in three of six cells. Apamin (100 nM) had no affect on AP repolarization, duration, or latency to AP generation, but did decrease the hyperpolarizing afterpotential (HAP). Inhibition of L-type VDCCs by nifedipine also decreased HAP amplitude. Inhibition of CICR by either thapsigargin or ryanodine treatment increased the number of APs generated with long depolarizing current pulses, whereas exposure to IBX or omega-conotoxin GVIA depressed excitability. We conclude that CICR, the process responsible for SMH generation, represents a unique mechanism to modulate the response to subthreshold depolarizing currents that drive the membrane potential toward the threshold for AP initiation but does not contribute to AP repolarization. Subthreshold depolarizations would not activate sufficient numbers of VDCCs to allow Ca(2+) influx to elevate [Ca(2+)](i) to the extent needed to directly activate nearby BK channels. However, the elevation in [Ca(2+)](i) is sufficient to trigger CICR from ryanodine-sensitive Ca(2+) stores. Thus CICR acts as an amplification mechanism to trigger a local elevation of [Ca(2+)](i) near a cluster of BK channels to activate these channels at negative levels of membrane potential.

Action Potentials↗