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At least 127 records · Page 7Linked to original sources

Three-dimensional color Doppler: a new approach for quantitative assessment of mitral regurgitant jets.

Color Doppler echocardiography does not provide adequate information about the severity of mitral regurgitation in patients with eccentric mitral regurgitation. We have developed a new procedure for 3-dimensional (3D) color Doppler reconstruction and for segmentation of regurgitant jets. The volume of regurgitant jets was compared with jet area in 63 patients with mitral regurgitation. Mitral regurgitation was assessed by angiography, regurgitant fraction and volume by pulsed Doppler, JA by planimetry, and JV by 3-dimensional Doppler. Twenty-eight patients with central jets were compared with 35 patients with eccentric jets. In the patients with eccentric jets, JV showed significant correlations with regurgitant volume (r = 0.90; P <.01) and regurgitant fraction (r = 0.76; P < .01) and was able to separate groups with different degrees of mitral regurgitation (P <.01). Three-dimensional Doppler revealed origin, direction, and spatial spreading of complex jet geometry. JV, a new parameter of mitral regurgitation, was also capable of quantifying asymmetrical jets.

Echocardiography, Doppler, Color↗

[Combined chemoradiotherapy of tumors in the child].

The high chemosensitivity of pediatric tumors along with their natural propensity for an early distant dissemination have stimulated the interest for chemo-radiation combinations in children since the mid 50s. Following the early experiments in nephroblastomas on the interaction of Actinomycin-D and radiotherapy, multiple national and international studies have been conducted since the mid 70s with considerable success: nowadays most pediatric tumors enjoy a long term survival in excess of 70%. Like their adult counterparts, these associations aim to induce an early control of the primary tumor and distant spreading (spatial cooperation) but also, more specifically in children, to limit the toxicity on normal tissues when treatment intensity can be further reduced. The association of an initial chemotherapy followed by local radiation at a dose and in a volume adapted to the response to chemotherapy along with associated prognostic factors has become widely tested in national and international studies conducted in Hodgkin's disease, Ewing's sarcoma, medulloblastomas, and brain tumors in the very young. Conversely, concomitant associations have remained limited to high-risk subgroups (parameningeal rhabdomyosarcomas for example) due to their potential hazards.

Adult↗

Rapid detection of threshold VEPs.

OBJECTIVE: To determine whether a one-dimensional (1D) Laplacian analysis detects steady-state visual evoked potentials (ssVEPs) faster than the standard O(z)-F(z) montage and to establish the optimum position of Laplacian reference electrodes. METHODS: Twenty-two normal adults were shown reversing checks ranging from 1.5' to 60'. Three electrode montages were investigated: O(z)-F(z), LO-F(z) and a 1D Laplacian analysis of 3 occipital electrodes (2O(z)-(RO+LO)). RO and LO were placed symmetrically and horizontally about O(z). Five different locations for RO and LO were investigated. Recordings were analysed in the frequency domain and the presence (and detection time, DT) or absence of a ssVEP defined statistically. Effects of individual, reference electrode site and check size on DT and phase differences between recording montages were investigated. RESULTS: Laplacian analysis detected ssVEPs to small (3') checks faster than O(z)-F(z), by 12.3 and 4.1s on average with Laplacian reference electrodes at 15 and 20% of half-head circumference, respectively. The optimum position of reference electrodes was governed by the instantaneous spatial spread of the response and the noise coherence between midline and lateral electrodes. CONCLUSIONS: A 1D Laplacian analysis can reduce the time to statistical detection of ssVEPs compared to the traditional O(z)-F(z) recording for stimuli near the normal acuity threshold of adults. This in turn could be used to minimise the length of a VEP acuity assessment.

Adult↗

State dependent excitability changes of spinal flexor reflex in patients with restless legs syndrome secondary to chronic renal failure.

OBJECTIVE: Periodic limb movement in sleep (PLMS) is a common dysfunction of motor control during sleep, occurring either in isolation or associated with a variety of neurological disorders including restless legs syndrome (RLS). Although the PLMS generators have not been established, their occurrence in patients with spinal cord injury and their clinical resemblance to the spinal cord flexor withdrawal reflex (FR) suggest that PLMS may originate in the circuitry that mediates the FR. The significantly increased spinal cord excitability noted in primary RLS/PLMS patients may play an important role in the pathophysiology of primary RLS. The aim of this study is to establish whether the enhanced spinal cord excitability, which is represented by a lower threshold and/or greater spatial spread of the FR, is also true for the RLS/PLMS patients whose RLS is secondary to chronic renal failure (CRF). METHODS: Twenty patients with RLS/PLMS secondary to CRF have been compared with matched controls according to the state dependent changes in FR excitability. All patients met the diagnostic criteria for RLS and PLMS. They had CRF for 5.2+/-3.5 years, and were under the hemodialysis treatment. Twenty healthy, age and sex matched subjects were tested as controls. The electrophysiological testing of the FR was performed during wakefulness (9:30-10:30 p.m.) and sleep (beginning of stage II, the first sleep cycle). RESULTS: A significant increase in FR excitability was found in RLS/PLMS patients with CRF. This abnormality was prominent during sleep, which was also true for the primary RLS. CONCLUSIONS: Our results suggest that similar neuronal pathways are involved in primary and secondary RLS/PLMS patients. Our results also support that RLS/PLMS and FR share a common spinal mechanism.

Journal Article↗

The analysis of synaptically generated traveling waves.

Mathematical and computational models for the propagation of activity in excitatorily coupled neurons are simulated and analyzed. The basic measurable quantity--velocity--is found for a wide class of models. Numerical bifurcation techniques, asymptotic analysis, and numerical simulations are used to show that there are distinct scaling laws for the velocity as a function of a variety of parameters. In particular, the obvious linear relationships between speed and spatial spread or synaptic decay rate are shown. More surprisingly, it is shown that the velocity scales as a power law with synaptic coupling strength and that the exponent is dependent only on the rising phase of the synapse.

Animals↗

Summation of spatiotemporal input patterns in leaky integrate-and-fire neurons: application to neurons in the cochlear nucleus receiving converging auditory nerve fiber input.

The response of leaky integrate-and-fire neurons is analyzed for periodic inputs whose phases vary with their spatial location. The model gives the relationship between the spatial summation distance and the degree of phase locking of the output spikes (i.e., locking to the periodic stochastic inputs, measured by the synchronization index). The synaptic inputs are modeled as an inhomogeneous Poisson process, and the analysis is carried out in the Gaussian approximation. The model has been applied to globular bushy cells of the cochlear nucleus, which receive converging inputs from auditory nerve fibers that originate at neighboring sites in the cochlea. The model elucidates the roles played by spatial summation and coincidence detection, showing how synchronization decreases with an increase in both frequency and spatial spread of inputs. It also shows under what conditions an enhancement of synchronization of the output relative to the input takes place.

Action Potentials↗

Characterization of a dextran-based bifunctional calcium indicator immobilized in cells by the enzymatic addition of isoprenoid lipids.

Cellular processes can be controlled by cell-wide increases in the cytosolic Ca2+ concentration or, alternatively, by localized Ca2+ signals in micro- and nano-domains. The experimental characterization of such localized Ca2+ signals would be facilitated using an immobilized Ca2+ indicator, which could prevent the accelerated spatial spreading of Ca2+ ions that is mediated by binding to diffusible indicators. Here we characterize a dextran-based Ca2+ indicator (CAAX-green) that becomes immobilized in the cytosol by an enzyme-mediated addition of a geranylgeranyl lipid group. CAAX-green consists of a dextran backbone with an attached Ca(2+)-green as well as an 11 residue peptide ending in a C-terminal CAAX-motif. Once introduced into cells by microporation, geranylgeranyl lipid groups are attached to the CAAX peptides by cytosolic enzymes. Measurements in tumor mastcells, myocytes and fibroblasts showed that the indicator becomes membrane attached between 30 min and 1 h following incorporation into the cytoplasm. A time-dependent 10-fold reduction of the diffusion coefficient and a parallel increase in the cytosolic retention after permeabilization indicates that at least 90% of cellular CAAX-green is immobilized. The KD of the indicator in permeabilized cells is 0.65 microM. Overall, these properties make CAAX-green well suited for the investigation of localized Ca2+ signals in a variety of cell types.

Animals↗

A new diagnostic procedure for assessing intracardiac flow disturbances in patients with heart valve disease.

BACKGROUND: Until now no diagnostic technique was available for the three-dimensional (3D) study of intracardiac blood flow abnormalities in patients with heart valve disease. 3D color Doppler is a new diagnostic technique first developed at our institution. METHODS: The 3D reconstructions of the blood flow velocity data have been obtained from conventional multiplanar transesophageal or transthoracic Doppler echocardiographic examinations. We analyzed 111 reconstructions of color Doppler data obtained from 85 patients with different heart valve diseases who underwent intraoperative transesophageal echocardiography. Sixty-nine patients had a significant mitral regurgitation, 7 mitral stenosis, 9 aortic regurgitation, 12 aortic stenosis, 14 tricuspid regurgitation. Three patients had pulmonary regurgitation associated with mitral valve disease. RESULTS: 3D color Doppler disclosed the complex spatial spreading of the blood flow abnormalities caused by heart valve disease. New patterns of intracardiac blood flow disturbances could be observed and classified. CONCLUSIONS: This paper shows the first clinical applications of 3D color Doppler in patients with heart valve disease. The new insights derived from the 3D study of intracardiac blood flow dynamics revealed a great impact of this technique on the clinical management of patients with heart valve disease.

Coronary Circulation↗

Dynamics of dendritic calcium transients evoked by quantal release at excitatory hippocampal synapses.

Synaptic N-methyl-D-aspartate (NMDA) receptors detect coincident pre- and postsynaptic activity and play a critical role in triggering changes in synaptic strength at central synapses. Despite intensive study of synaptic plasticity, relatively little is known about the magnitude and duration of calcium accumulation caused by unitary events at individual synapses. We used fluorescence imaging to detect NMDA receptor-mediated miniature synaptic calcium transients (MSCTs) caused by spontaneous release of synaptic vesicles in dendrites of cultured hippocampal neurons. MSCTs originated focally in dendritic regions <1 microm in length and decayed with a time constant of 0.35 +/- 0.03 s. Multiple occurrences of MSCTs recorded at single sites had fluctuating amplitudes, with a coefficient of variation of 0.34. From the reduction in the spatial spread of MSCTs with decreasing concentration of indicator dye, we estimated that the dominant endogenous calcium buffer in dendrites is relatively immobile (diffusion coefficient between 10 and 50 microm(2)/s). We conclude that calcium rise caused by spontaneous quantal synaptic NMDA receptor activation (i) is variable, (ii) lasts for a time period briefer than previous measurements indicate, and (iii) is confined by endogenous calcium buffers to local dendritic regions even when synapses are not on spines.

Aniline Compounds↗

Cyclic ADP-ribose enhances coupling between voltage-gated Ca2+ entry and intracellular Ca2+ release.

Ca2+ release from intracellular stores can be activated in neurons by influx of Ca2+ through voltage-gated Ca2+ channels. This process, called Ca2+-induced Ca2+ release, relies on the properties of the ryanodine receptor and represents a mechanism by which Ca2+ influx during neuronal activity can be amplified into large intracellular Ca2+ signals. In a differentiated neuroblastoma cell line, we show that caffeine, a pharmacological activator of the ryanodine receptor, released Ca2+ from intracellular stores in a Ca2+-dependent and ryanodine-sensitive manner. The pyridine nucleotide, cyclic ADP-ribose, thought to be an endogenous modulator of ryanodine receptors also amplified Ca2+-induced Ca2+ release in these neurons. Cyclic ADP-ribose enhanced the total cytoplasmic Ca2+ levels during controlled Ca2+ influx through voltage gated channels, in a concentration-dependent and ryanodine-sensitive manner and also increased the sensitivity with which a small amount of Ca2+ influx could trigger additional release from the ryanodine-sensitive intracellular Ca2+ stores. Single cell imaging showed that following the Ca2+ influx, cyclic ADP-ribose enhanced the spatial spread of the Ca2+ signal from the edge of the cell into its center. These powerful actions suggest a role for cyclic ADP-ribose in the functional coupling of neuronal depolarization, Ca2+ entry, and global intracellular Ca2+ signaling.

Adenosine Diphosphate Ribose↗

CHOLINESTERASE IN DENERVATED END PLATES AND MUSCLE FIBRES.

Parallel studies were made of cholinesterase activities and localizations in denervated rat and rabbit gastrocnemius muscle. Koelle's histochemical reaction was used for demonstrating the localization of cholinesterases. Enzyme activities in whole sliced muscle were measured by electrometric titration. The Cartesian ampulla-diver technique was used for cholinesterase activity determinations in end plate regions or in small pieces of the muscle fibre itself. No changes in the activity of cholinesterases (ChE) were found in the whole denervated muscle which would account for its chemical supersensitivity. The ChE distribution pattern was changed so that the end plate region became less active in the denervated muscle than in the normal one. The decrease in ChE activity in the end plates seems to be largely compensated for by an increase of this enzyme elsewhere in the muscle. A possible connection between the spatial spread of cholinesterase activity and the enlargement of the acetylcholine-sensitive surface is discussed.

Acetylcholine↗

Caffeine- and ryanodine-sensitive Ca(2+)-induced Ca2+ release from the endoplasmic reticulum in honeybee photoreceptors.

Light stimulation of invertebrate microvillar photoreceptors causes a large rapid elevation in Cai, shown previously to modulate the adaptational state of the cells. Cai rises, at least in part, as a result of Ins(1,4,5)P3-induced Ca2+ release from the submicrovillar endoplasmic reticulum (ER). Here, we provide evidence for Ca(2+)-induced Ca2+ release (CICR) in an insect photoreceptor. In situ microphotometric measurements of Ca2+ fluxes across the ER membrane in permeabilized slices of drone bee retina show that (a) caffeine induces Ca2+ release from the ER; (b) caffeine and Ins(1,4,5)P3 open distinct Ca2+ release pathways because only caffeine-induced Ca2+ release is ryanodine sensitive and heparin insensitive, and because caffeine and Ins(1,4,5)P3 have additive effects on the rate of Ca2+ release; (c) Ca2+ itself stimulates release of Ca2+ via a ryanodine-sensitive pathway; and (d) cADPR is ineffective in releasing Ca2+. Microfluorometric intracellular Ca2+ measurements with fluo-3 indicate that caffeine induces a persistent elevation in Cai. Electrophysiological recordings demonstrate that caffeine mimics all aspects of Ca(2+)-mediated facilitation and adaptation in drone photoreceptors. We conclude that the ER in drone photoreceptors contains, in addition to the Ins(1,4,5)P3-sensitive release pathway, a CICR pathway that meets key pharmacological criteria for a ryanodine receptor. Coexpression of both release mechanisms could be required for the production of rapid light-induced Ca2+ elevations, because Ca2+ amplifies its own release through both pathways by a positive feedback. CICR may also mediate the spatial spread of Ca2+ release from the submicrovillar ER toward more remote ER subregions, thereby activating Ca(2+)-sensitive cell processes that are not directly involved in phototransduction.

Adenosine Diphosphate Ribose↗

Changes in membrane characteristics of heart muscle during inhibition.

Membrane characteristics were studied in isolated muscle strands from auricles of frogs using the "square pulse" technique. Changes in the time course and spatial spread of subthreshold electrotonic potentials were measured. If acetylcholine is applied in concentrations which cause slowing or stoppage of the heart beat, the following changes are produced: (a) the length constant (lambda) of the membrane is reduced, (b) the time constant is shortened. The effects are reversible and increase with acetylcholine concentration. The membrane changes caused by acetylcholine dimmish with time. It is concluded that during acetylcholine inhibition, as well as during vagal inhibition, the conductance of the muscle membrane is increased. Appreciable changes in the resting membrane potential need not accompany inhibition.

Acetylcholine↗

Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie.

Both infectivity and TSE-specific amyloid protein (also referred to as protease resistant- or prion protein, PrP) are pathognomonic markers for transmissible spongiform encephalopathies (TSE). This paper presents a new densitometric method for the quantification of TSE-specific amyloid protein and its application to studying the pathogenesis of scrapie in Syrian hamsters after infection with scrapie strain 263K. A first study established a close correlation between infectivity and TSE-specific amyloid protein with a doubling time of 2-2.6 days in the brain and cervical spinal cord for both markers. The ratio of infectivity and TSE-specific amyloid protein was relatively constant at a mean value of about 10(6) protein molecules per infectious unit during the course of infection. A subsequent study addressed the temporal-spatial spread of infection in the central nervous system by tracing the accumulation of the pathological protein. The pathogenetic process was first detected in the spinal cord between vertebrae T4 and T9, and then showed an anterograde and retrograde spread with a rate of 0.8-1.0 mm/day. There were also some indications for a possible alternative route of spread of infection from the periphery to the brain, other than via the spinal cord. Involvement of the spleen did not appear essential for the early pathogenesis in hamsters orally infected with the 263K strain of scrapie.

Administration, Oral↗

Concentrations of atmospheric sulfur compounds in an extremely snowy region, the Hokuriku District, Japan.

The diurnal and seasonal characteristics in gaseous sulfur dioxide and sulfate in aerosol particles, as well as the concentrations of sulfate in rain and snow, were measured in the Hokuriku District, Japan in order to investigate the spatial spread pattern of sulfur compounds and identify the origin of sulfur. The concentration of sulfur dioxide showed a distinct diurnal pattern, while the concentrations of nss-SO4(2-) in precipitation and aerosol particles did not. These results implied that the sulfur dioxide might originate in local emissions and did not affect the concentration of nss-SO4(2-) in precipitation, while nss-SO4(2-) in aerosol particles seemed to be widespread and might result from long-range transportation. The deposition of nss-SO42- in precipitation increased in winter, while the concentration of nss-SO4(2-) in aerosol particles decreased. This could be attributed to the lower cloud base often observed in this district in winter associated with a higher washout ratio.

Aerosols↗

Nanoscale imaging of electronic surface transport probed by atom movements induced by scanning tunneling microscope current.

The hopping movements of Cl atoms on a Si(111)-(7 x 7) surface that are enhanced by an electron injection from tips of a scanning tunneling microscope (STM) exhibit a spatial spread from the electron injection point with an anisotropic distribution. The enhanced hopping effect becomes greatest at a sample bias voltage being resonant with the Si-Cl antibonding states and also exhibits an oscillatory decay with the distance from the injection point characterized by the wavelength depending on the bias voltage. All of these facts can be interpreted in terms of the coherent expansion of the electron wave packets locally formed at the STM tip.

Journal Article↗

A continuum of InsP3-mediated elementary Ca2+ signalling events in Xenopus oocytes.

1. The elementary release events underlying inositol 1,4, 5-trisphosphate (InsP3)-mediated calcium signalling were investigated in Xenopus oocytes by means of high-resolution confocal linescan imaging together with flash photolysis of caged InsP3. 2. Weak photolysis flashes evoked localized, transient calcium signals that arose at specific sites following random latencies of up to several seconds. The duration, spatial spread and amplitude of these elementary events varied widely. Event durations (at half-maximal amplitude) were distributed exponentially between about 100 and 600 ms. Fluorescence magnitudes (F/F0 of Oregon Green 488 BAPTA-1) showed a skewed distribution with a peak at about 1.5 and a tail extending as high as 3.5. 3. Individual release sites exhibited both small events (blips) and large events (puffs). The spatiotemporal distribution of calcium signals during puffs was consistent with calcium diffusion from a point source (< a few hundred nanometres), rather than with propagation of a microscopic calcium wave. 4. Estimates of the calcium flux associated with individual events were made by integrating fluorescence profiles along the scan line in three dimensions to derive the 'signal mass' at each time point. The smallest resolved events corresponded to liberation of < 2 x 10-20 mol Ca2+, and large events to about 2 x 10-18 mol Ca2+. The rise of signal mass was more prolonged than that of the fluorescence intensity, suggesting that calcium liberation persists even while the fluorescence begins to decline. Rates of rise of signal mass corresponded to Ca2+ currents of 0.4-2.5 pA. 5. Measurements of signal mass from different events showed a continuous, exponential distribution, arising through variability in magnitude and duration of calcium flux. 6. We conclude that localized calcium transients in the oocyte represent a continuum of events involving widely varying amounts of calcium liberation, rather than falling into separate populations of 'fundamental' and 'elementary' events (blips and puffs) involving, respectively, single and multiple InsP3 receptor channels. This variability probably arises through stochastic variation in both the number of channels recruited and the duration of channel opening.

Animals↗

Focal agonist stimulation results in spatially restricted Ca2+ release and capacitative Ca2+ entry in bovine vascular endothelial cells.

1. Intracellular Ca2+ ([Ca2+]i) signals were studied with spatial resolution in bovine vascular endothelial cells using the fluorescent Ca2+ indicator fluo-3 and confocal laser scanning microscopy. Single cells were stimulated with the purinergic receptor agonist ATP resulting in an increase of [Ca2+]i due to intracellular Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive stores. ATP-induced Ca2+ release was quantal, i.e. submaximal concentrations mobilized only a fraction of the intracellularly stored Ca2+. 2. Focal receptor stimulation in Ca2+-free solution by pressure application of agonist-containing solution through a fine glass micropipette resulted in a spatially restricted increase in [Ca2+]i. Ca2+ release was initiated at the site of stimulation and frequently propagated some tens of micrometres into non-stimulated regions. 3. Local Ca2+ release caused activation of capacitative Ca2+ entry (CCE). CCE was initially colocalized with Ca2+ release. Following repetitive focal stimulation, however, CCE became detectable at remote sites where no Ca2+ release had been observed. In addition, the rate of Ca2+ store depletion with repetitive local activation of release in Ca2+-free solution was markedly slower than that elicited by ATP stimulation of the entire cell. 4. From these experiments it is concluded that both intracellular IP3-dependent Ca2+ release and activation of CCE are controlled locally at the subcellular level. Moreover, redistribution of intracellular Ca2+ stored within the endoplasmic reticulum efficiently counteracts local store depletion and accounts for the spatial spread of CCE activation.

Action Potentials↗