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PubMed1993

Normal polyspecific immunoglobulin G (IVIg) in the treatment of autoimmune diseases.

Infusion of intravenous immunoglobulin (IVIg) has resulted in clinical improvement and/or a fall in autoantibody in a number of autoimmune and inflammatory diseases. Several lines of evidence demonstrate that IVIg may react with disease-associated autoantibodies through idiotypic interactions. In addition, infusion of IVIg results in changes in the expressed autoantibody repertoire that are dependent on interactions between variable regions of infused IgG and autoantibodies and in the subsequent alterations in the regulatory function of immune networks. Thus, pooled normal immunoglobulin restored in a patient with autoimmune thyroiditis the dynamics of spontaneous fluctuations of serum autoantibodies characteristic of physiological conditions. The ability of IVIg to interact with V regions of autoantibodies and with surface molecules of lymphocytes in vitro provides a basis for the selective modulation of B-cell clones observed in patients treated with immunoglobulins. The natural intrinsic complexity of IVIg provides a physiological rationale for immunoregulatory therapy of autoimmune disease.

Antibodies, Anti-Idiotypic↗
PubMed1992

Variations in expression and treatment of transient neurocardiogenic instability.

Whereas previous reports describe the head-up tilt test for the diagnosis of neurocardiogenic syncope, this study focuses on the events leading up to syncope. These events are part of a spectrum of neurocardiogenic instability; syncope is the extreme end point. This report is based on tilt studies of 108 patients, aged 4 to 22 years (mean 13), with histories of either unexplained syncope or episodes of visual blackout without loss of consciousness. The tilt study was positive in 74% of the patients. Five stages of neurocardiogenic instability were identified, ranging from excessive fluctuations in heart rate to full syncope. Uncommon reactions during the tilt study include dissociation of hypotension, bradycardia and vagal symptoms and extended asystole (greater than 6 seconds). Therapy with beta 1-selective blockers was highly successful in suppressing symptoms of neurocardiogenic instability. Repeat tilt testing with beta blockade has resulted in either normal or markedly improved stability in heart rate and blood pressure. Neurocardiogenic instability is a common condition occurring between age 10 and 20 years. It appears to be self-limited.

Adolescent↗
PubMed2006

Factors associated with depression in Parkinson's disease: a cross-sectional study in a Polish population.

OBJECTIVE: The aim of this study was to assess the prevalence and factors influencing depression in PD patients in a cross-sectional outpatient clinic - based Polish patients sample. MATERIALS AND METHODS: One hundred consecutive PD patients were included in this study; 35 of them fulfilled DSM-IV criteria for Major Depression and its severity was assessed with Montgomery-Asberg Depression Rating Scale (MADRS). A structured interview and a neurological examination, including Hoehn and Yahr scale (H-Y), Schwab-England disability scale, II, III, IV parts of Unified Parkinson's Disease Rating Scale (UPDRS), and Mini-Mental State Examination (MMSE) were performed. The parameters obtained were analysed between the depressed and non-depressed PD patients. RESULTS: The prevalence of depression in PD in Polish population was established at the level of 35%. PD patients with depression scored significantly higher in all UPDRS scales (except for the subscale of clinical fluctuation) and in H-Y scale. PD with depression was also associated with longer PD duration, higher doses of L-dopa equivalents, patients' age, general impairment of daily living in Schwab and England disability scale, lower MMSE and higher clinical fluctuations. However, those six differences were insignificant. CONCLUSIONS: Depression prevalence rate among PD patients in Polish population is slightly lower than in most of other published studies. This may result from strict selection criteria, use of specific outcome measures and restricted criteria for depression that were applied.

Adult↗
PubMed2004

Deep brain stimulation surgery for Parkinson's disease: mechanisms and consequences.

Despite the introduction of new medications, motor fluctuations and dyskinesias disable a significant proportion of Parkinson's disease patients. This has lead to renewed interest in stereotactic neurosurgery. A skilled team is needed to ensure that patient assessment and selection, operative technique, intraoperative monitoring, and post-operative management are optimised. High frequency stimulation has similar effects to ablative surgery, and is generally preferred. The clinical effects and possible mechanisms of action of deep brain stimulation of the subthalamic nucleus and globus pallidus are reviewed.

Animals↗
PubMed2002

Interaction of hagfish cathelicidin antimicrobial peptides with model lipid membranes.

Hagfish intestinal antimicrobial peptides (HFIAPs) are a family of polycationic peptides exhibiting potent, broad-spectrum bactericidal activity. In an attempt to unravel the mechanism of action of HFIAPs, we have studied their interaction with model membranes. Synthetic HFIAPs selectively bound to liposomes mimicking bacterial membranes, and caused the release of vesicle-encapsulated fluorescent markers in a size-dependent manner. In planar lipid bilayer membranes, HFIAPs induced erratic current fluctuations and reduced membrane line tension according to a general theory for lipidic pores, suggesting that HFIAP pores contain lipid molecules. Consistent with this notion, lipid transbilayer redistribution accompanied HFIAP pore formation, and membrane monolayer curvature regulated HFIAP pore formation. Based on these studies, we propose that HFIAPs kill target cells, at least in part, by interacting with their plasma membrane to induce formation of lipid-containing pores. Such a membrane-permeabilizing function appears to be an evolutionarily conserved host-defense mechanism of antimicrobial peptides.

Animals↗
PubMed2005

Far-field optical microscopy of single metal nanoparticles.

Individual noble-metal particles, with sizes ranging from a few tenths to some hundreds of nanometers, can now be detected by far-field optics. Single-particle microscopy gives access to inhomogeneity, distributions, and fluctuations, which were previously hidden in ensemble experiments. Scattering methods rely on dark-field illumination, spectral signatures of the metal particles, or both. More advanced techniques provide high sensitivity and improved selectivity with respect to other scatterers by isolating metal-specific signals, for example the refractive index change due to heating of the environment by a pump beam or the time-resolved optical response of the particle to a short pump pulse. We review and compare linear and nonlinear methods in far-field optical microscopy that have reached the single-particle regime by means of scattered light, thermal effects, photoluminescence, or nonlinear frequency generation.

Journal Article↗
PubMed1999

Quantitative electron spectroscopic diffraction analyses of the crystal formation in dentine.

Newly formed apatitic crystallites of different hard tissues consist, according to our investigations, of chains composed of nanometre-sized particles (islands, dots) arising at nucleating sites of the collagenous and noncollagenous matrix macromolecules. In dentine these islands coalesce rapidly in longitudinal direction to form needle-like crystallites which further coalesce to ribbon-like crystallites. We have concluded that the centre-to-centre distances between these islands represent the distances between the nucleating sites of the matrix macromolecules. We have applied energy-filtering transmission electron microscopy in the selected area electron diffraction mode at different stages of crystal formation in dentine and have obtained quantitative information of the degree of crystal disorder on the basis of the paracrystal theory. The fluctuation of the lattice plane distances in c-axis direction decreases, proceeding from the region near the dentine/predentine border to the dentine/enamel border.

Animals↗
PubMed2004

An effective kinetic representation of fluctuation-driven neuronal networks with application to simple and complex cells in visual cortex.

A coarse-grained representation of neuronal network dynamics is developed in terms of kinetic equations, which are derived by a moment closure, directly from the original large-scale integrate-and-fire (I&F) network. This powerful kinetic theory captures the full dynamic range of neuronal networks, from the mean-driven limit (a limit such as the number of neurons N --> infinity, in which the fluctuations vanish) to the fluctuation-dominated limit (such as in small N networks). Comparison with full numerical simulations of the original I&F network establishes that the reduced dynamics is very accurate and numerically efficient over all dynamic ranges. Both analytical insights and scale-up of numerical representation can be achieved by this kinetic approach. Here, the theory is illustrated by a study of the dynamical properties of networks of various architectures, including excitatory and inhibitory neurons of both simple and complex type, which exhibit rich dynamic phenomena, such as, transitions to bistability and hysteresis, even in the presence of large fluctuations. The implication for possible connections between the structure of the bifurcations and the behavior of complex cells is discussed. Finally, I&F networks and kinetic theory are used to discuss orientation selectivity of complex cells for "ring-model" architectures that characterize changes in the response of neurons located from near "orientation pinwheel centers" to far from them.

Computer Simulation↗
PubMed2005

Force requirements and insulin delivery profiles of four injection devices.

BACKGROUND: Injection force requirements for four insulin pen-type injection devices were evaluated using the AGS-IkNG Autograph force measurement device (Shimadzu Corp., Kyoto, Japan). RESULTS: Compared with the Humulin Pen (the Japanese brand name is Humacart kit; the same device as the Humalog Pen; Eli Lilly, Indianapolis, IN), HumaPen Ergo (Eli Lilly), and NovoPen 3 (Novo Nordisk A/S, Bagsvaerd, Denmark), the InnoLet(Novo Nordisk) required the lowest injection force to both initiate piston movement and commence insulin delivery and required the lowest overall force throughout delivery. InnoLet and NovoPen 3 showed the most even load-displacement curves, suggesting a smoother delivery of insulin during injection. In contrast, the Humulin Pen and HumaPen Ergo demonstrated marked fluctuations in the force required to complete injection. CONCLUSIONS: These performance characteristics appeared consistent with mechanical features of these insulin delivery devices, and the results highlight the potential importance of careful pen selection for patients with neuromuscular weakness or impaired manual coordination.

Diabetes Mellitus↗
PubMed2004

Learning in neural networks by reinforcement of irregular spiking.

Artificial neural networks are often trained by using the back propagation algorithm to compute the gradient of an objective function with respect to the synaptic strengths. For a biological neural network, such a gradient computation would be difficult to implement, because of the complex dynamics of intrinsic and synaptic conductances in neurons. Here we show that irregular spiking similar to that observed in biological neurons could be used as the basis for a learning rule that calculates a stochastic approximation to the gradient. The learning rule is derived based on a special class of model networks in which neurons fire spike trains with Poisson statistics. The learning is compatible with forms of synaptic dynamics such as short-term facilitation and depression. By correlating the fluctuations in irregular spiking with a reward signal, the learning rule performs stochastic gradient ascent on the expected reward. It is applied to two examples, learning the XOR computation and learning direction selectivity using depressing synapses. We also show in simulation that the learning rule is applicable to a network of noisy integrate-and-fire neurons.

Action Potentials↗
PubMed2006

Thermal evolution of pre-adult life history traits, geometric size and shape, and developmental stability in Drosophila subobscura.

Replicated lines of Drosophila subobscura originating from a large outbred stock collected at the estimated Chilean epicentre (Puerto Montt) of the original New World invasion were allowed to evolve under controlled conditions of larval crowding for 3.5 years at three temperature levels (13, 18 and 22 degrees C). Several pre-adult life history traits (development time, survival and competitive ability), adult life history related traits (wing size, wing shape and wing-aspect ratio), and wing size and shape asymmetries were measured at the three temperatures. Cold-adapted (13 degrees C) populations evolved longer development times and showed lower survival at the highest developmental temperature. No divergence for wing size was detected following adaptation to temperature extremes (13 and 22 degrees C), in agreement with earlier observations, but wing shape changes were obvious as a result of both thermal adaptation and development at different temperatures. However, the evolutionary trends observed for the wing-aspect ratio were inconsistent with an adaptive hypothesis. There was some indication that wing shape asymmetry has evolutionarily increased in warm-adapted populations, which suggests that there is additive genetic variation for fluctuating asymmetry and that it can evolve under rapid environmental changes caused by thermal stress. Overall, our results cast strong doubts on the hypothesis that body size itself is the target of selection, and suggest that pre-adult life history traits are more closely related to thermal adaptation.

Animals↗
PubMed2002

Spectro-temporal processing in the envelope-frequency domain.

The frequency selectivity for amplitude modulation applied to tonal carriers and the role of beats between modulators in modulation masking were studied. Beats between the masker and signal modulation as well as intrinsic envelope fluctuations of narrow-band-noise modulators are characterized by fluctuations in the "second-order" envelope (referred to as the "venelope" in the following). In experiment 1, masked threshold patterns (MTPs), representing signal modulation threshold as a function of masker-modulation frequency, were obtained for signal-modulation frequencies of 4, 16, and 64 Hz in the presence of a narrow-band-noise masker modulation, both applied to the same sinusoidal carrier. Carrier frequencies of 1.4, 2.8, and 5.5 kHz were used. The shape and relative bandwidth of the MTPs were found to be independent of the signal-modulation frequency and the carrier frequency. Experiment 2 investigated the extent to which the detection of beats between signal and masker modulation is involved in tone-in-noise (TN), noise-in-tone (NT), and tone-in-tone (TT) modulation masking, whereby the TN condition was similar to the one used in the first experiment. A signal-modulation frequency of 64 Hz, applied to a 2.8-kHz carrier, was tested. Thresholds in the NT condition were always lower than in the TN condition, analogous to the masking effects known from corresponding experiments in the audio-frequency domain. TT masking conditions generally produced the lowest thresholds and were strongly influenced by the detection of beats between the signal and the masker modulation. In experiment 3, TT masked-threshold patterns were obtained in the presence of an additional sinusoidal masker at the beat frequency. Signal-modulation frequencies of 32, 64, and 128 Hz, applied to a 2.8-kHz carrier, were used. It was found that the presence of an additional modulation at the beat frequency hampered the subject's ability to detect the envelope beats and raised thresholds up to a level comparable to that found in the TN condition. The results of the current study suggest that (i) venelope fluctuations play a similar role in modulation masking as envelope fluctuations do in spectral masking, and (ii) envelope and venelope fluctuations are processed by a common mechanism. To interpret the empirical findings, a general model structure for the processing of envelope and venelope fluctuations is proposed.

Adult↗
PubMed2005

Multi-site recording and spectral analysis of spontaneous photon emission from human body.

BACKGROUND: In the past years, research on ultraweak photon emission (UPE) from human body has increased for isolated cells and tissues. However, there are only limited data on UPE from the whole body, in particular from the hands. OBJECTIVE: To describe a protocol for the management of subjects that (1) avoids interference with light-induced longterm delayed luminescence, and (2) includes the time slots for recording photon emission. MATERIAL AND METHODS: The protocol was utilised for multi-site recording of 4 subjects at different times of the day and different seasons, and for one subject to complete spectral analysis of emission from different body locations. An especially selected low-noise end-window photomultiplier was utilised for the detection of ultraviolet / visible light (200-650 nm) photon emission. For multi-site recording it was manipulated in three directions in a darkroom with a very low count rate. A series of cut-off filters was used for spectral analysis of UPE. 29 body sites were selected such that the distribution in UPE could be studied as right-left symmetry, dorsal-ventral symmetry, and the ratio between the central body part and extremities. RESULTS: Generally, the fluctuation in photon counts over the body was lower in the morning than in the afternoon. The thorax-abdomen region emitted lowest and most constantly. The upper extremities and the head region emitted most and increasingly over the day. Spectral analysis of low, intermediate and high emission from the superior frontal part of the right leg, the forehead and the palms in the sensitivity range of the photomultiplier showed the major spontaneous emission at 470-570 nm. The central palm area of hand emission showed a larger contribution of the 420-470 nm range in the spectrum of spontaneous emission from the hand in autumn/winter. The spectrum of delayed luminescence from the hand showed major emission in the same range as spontaneous emission. CONCLUSION: Examples of multi-site UPE recordings and spectral analysis revealed individual patterns and dynamics of spontaneous UPE over the body, and spectral differences over the body. The spectral data suggest that measurements might well provide quantitative data on the individual pattern of peroxidative and anti-oxidative processes in vivo. We expect that the measurements provide physiological information that can be useful in clinical examination.

Adult↗
PubMed1995

Pharmacokinetic-pharmacodynamic relationships for opioids in balanced anaesthesia.

The pure mu-receptor opioid agonists fentanyl, sufentanil and alfentanil are commonly used to provide the specific anti-nociceptive component of a balanced anaesthesia technique. Trefentanil and remifentanil are new opioids with a very short duration of action. Remifentanil has an ester structure and is very rapidly metabolised by blood and tissue esterases. Different perioperative stimuli require different plasma concentrations to suppress responses of the patient. The ability of the anaesthesiologist to select a precise dosage scheme for the individual patient is impeded by the large interindividual pharmacokinetic and pharmacodynamic variability. In addition, the combination of opioids and other drugs used to produce the desired components of balanced anaesthesia may exert additive, synergistic or antagonistic effects. Knowledge of factors influencing the pharmacokinetics and pharmacodynamics is still fragmentary and often controversial. Consequently, the opioid dose needs to be adjusted according to the responses of the patient during surgery to ensure adequate anaesthesia and rapid recovery. The duration of action is not predicted by the elimination half-life alone. The decline in effect-site concentration is dependent on the complex entity of infusion duration, and pharmacokinetic and pharmacodynamic parameters. Computer simulations of infusions of varying duration have been extremely useful when selecting an opioid for a specific clinical scenario on a rational basis. Traditionally, opioids are still administered by intermittent bolus injections. A disadvantage of this method of administration is that plasma concentrations fluctuate above and below the level required for adequate anaesthesia. Computer-assisted infusion pumps make it possible to target a particular drug concentration in plasma and to maintain or change this concentration as needed. This technique provides more stable anaesthesia and a more rapid recovery of the patient.

Analgesics, Opioid↗
PubMed1985

Fleischner lecture. Biokinetic impacts on structure and imaging of the lung: the concept of biologically closed electric circuits.

The corona complex of the lung is a collection of radiographic features surrounding a pulmonary mass. Each of its 12 components may be explained by a recently described subset of biologically closed electric circuits, the vascular-interstitial closed electric circuit (VICC) system. This system is activated both by normal metabolism of tissue and by local degrading processes, such as spontaneous necrosis or hemorrhage, that lead to local electrochemical polarization of a lesion in relation to surrounding noninjured tissue. Ions, cells, and water are transported electrically in the VICC system, leading to the development of the corona complex. The VICC system is conceived to exist with the walls of arteries and veins functioning as insulators around the electrically conducting medium of blood, the plasma. Blood vessels therefore connect electrically the injured and noninjured tissues. At the capillary level, electric junctions connect plasma and interstitial fluid, which functions as an electrical conductor comparable to blood plasma. The interstitial fluid therefore completes the circuit. The VICC system can be regarded as an additional circulatory system for selective electrogenic transports, coupled directly to the mechanical circulation of blood and lymph. The injury potential represents an important energetic factor in the activation of the VICC system. It is a slowly fluctuating, attenuating, electrochemical potential inducing ebb and flow of time-dependent anionic and cationic transports. The corona structures are special effects of the healing of injured tissue. The 12 radiologic signs of the corona complex have each been produced experimentally in vitro in animals and in vivo in humans during electrochemical treatment of cancers. The "A" zone is characterized radiographically by radiolucency around an electrically polarizing focal lesion. Peripheral to the A zone, a "B" zone is seen as a radiopaque region. The A and B zones are predominantly the result of an electroosmotic outflow of water from a lesion during its electropositive phase. At the interface between the A and B zones, small arches sometimes form an arcade. This configuration develops when the polarizing lesion has small protrusions at its surface. As a result of electrical edge enhancement, various elements of the interstitial tissue are transformed into radiating fibrous structures. They grow out at right angles to the surface of the lesion and serve as supporting columns for the arches. When necrotic material from a tumor is evacuated through a bronchus, ensuing collapse of the tumor will displace those radiating structures already produced.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed2002

Genetic parameters for various random regression models to describe the weight data of pigs.

Various random regression models have been advocated for the fitting of covariance structures. It was suggested that a spline model would fit better to weight data than a random regression model that utilizes orthogonal polynomials. The objective of this study was to investigate which kind of random regression model fits best to weight data of pigs. Two random regression models that described weight of individual pigs, one using orthogonal polynomials, and the other using splines, were compared. A comparison with a multivariate model, Akaike's information criterion, and the Bayesian-Schwarz information criterion were used to select the best model. Genetic, permanent environmental, and total variances increased with age. Heritabilities for the multivariate model ranged from 0.14 to 0.19, and for both random regression models the heritabilities were fluctuating around 0.17. Both genetic and phenotypic correlations decreased when the interval between measurements increased. The spline model needed fewer parameters than the multivariate and polynomial models. Akaike's information criterion was least for the spline model and greatest for the multivariate model. The Bayesian-Schwarz information criterion was least for the polynomial model and greatest for the multivariate model. Residuals of all models were normally distributed. Based on these results, it is concluded that random regression models provide the best fit to pig weight data.

Age Factors↗
PubMed2003

Long-term motor effect of unilateral pallidal stimulation in 26 patients with advanced Parkinson disease.

OBJECT: The aim of this study was to evaluate the long-term effects of unilateral pallidal stimulation on motor function in selected patients with advanced Parkinson disease (PD). METHODS: The authors enrolled 26 patients with idiopathic PD in whom there was an asymmetric distribution of symptoms and, despite optimal pharmocological treatment, severe response fluctuations and/or dyskinesias. After the patient had received a local anesthetic agent, a quadripolar electrode (Medtronic model 3387) was implanted at the side opposite the side affected or, if both sides were affected, the side contralateral to the more affected side. No serious complications occurred. After 3 months, the total Unified PD Rating Scale (UPDRS) Part III score decreased by 50.7% while patients were in the off-medication state (from 26.5 +/- 9.2 to 13.1 +/- 6.1) and by 55.4% while they were in the on-medication state (from 10.6 +/- 6.3 to 4.7 +/- 4.4). Only during the on state was the contralateral effect clearly more pronounced. The UPDRS Part IVa score decreased by 75% (from 3.7 +/- 2.5 to 0.9 +/- 1.1) and the UPDRS Part IVb score by 54.7% (from 3.3 +/- 1.3 to 1.5 +/- 1.3). At long-term follow-up review (32.7 +/- 10.7 months), there was an 8.3% increase in the UPDRS Part III score while patients were in the off state (from 26.5 +/- 9.2 to 28.7 +/- 7.6) and a 40.2% increase in this score while patients were in the on state (from 10.6 +/- 6.3 to 14.9 +/- 5.1). The UPDRS Part IVa score decreased by 28.1% (from 3.7 +/- 2.5 to 2.7 +/- 2.3) and the UPDRS Part IVb score increased by 3.5% (from 3.3 +/- 1.3 to 3.4 +/- 1.6). CONCLUSIONS: Based on these unsatisfactory results at long-term review, the authors conclude that unilateral pallidal stimulation is not an effective treatment option for patients with advanced PD.

Adult↗
PubMed2000

Influence of growth and environmental conditions on cell surface hydrophobicity of Pseudomonas fluorescens in non-specific adhesion.

The relative cell surface hydrophobicity (CSH) of 18 soil isolates of Pseudomonas fluorescens, determined by phase exclusion, hydrophobic interaction chromatography (HIC), electrostatic interaction chromatography (ESIC), and contact angle, revealed large degrees of variability. Variation in the adhesion efficiency to Macrophomina phaseolina of the hyphae/sclerotia of these isolates was also examined. Two such isolates with maximum (32.8%; isolate 12-94) and minimum (12%; isolate 30-94) CSH were selected for further study. Early- to mid-log exponential cells of these isolates were more hydrophobic than those in stationary phase, and the CSH of these isolates was also influenced by fluctuations in temperatures and pH. Isolate 12-94 exhibited high CSH (32.3%) at 30 degrees C, compared to lower values (28-24%) in the higher temperature range (35-40 degrees C). Increasing concentrations of either Zn2+, Fe3+, K+, and Mg2+ in the growth medium were associated with the increased CSH. Trypsin, pepsin, and proteinase K (75 to 150 micrograms.mL-1) reduced the CSH of isolate 12-94 cells. CSH was reduced, following exposure to DTT, SDS, Triton X-100, or Tween 80. Prolonged exposure of cells to starvation (60 days) also caused a significant decline in CSH. Several protein bands (18, 21, 23, 26 kDa) of the outer cell membrane were absent in 60-day starved cells compared to unstarved cells. In conclusion, our findings demonstrate that CSH of P. fluorescens isolates may contribute to nonspecific attachment/adhesion onto M. phaseolina hyphae/sclerotia, and the efficiency of adhesion is regulated by growth and other environmental conditions.

Bacterial Adhesion↗